School of Chemistry & Molecular Biosciences
Faculty of Science
BIOTECHNOLOGY
Research Projects 2016
Honours
Graduate Diploma
Masters
Masters Res Ex
Professional Doctorate
CONTENTS
Industry Contributors
Professor Ross Barnard
Professor Peter Gray
Associate Professor Peer Schenk
Professor Istvan Toth
Professor Matt Trau
INDUSTRY PROJECTS
Organisation/Business Unit
Director, Biotechnology Program
School of Chemistry & Molecular Biosciences
Australian Institute for Bioengineering and
Nanotechnology (AIBN)
School of Biological Sciences
School of Chemistry & Molecular Biosciences /
TETRAQ
Australian Institute for Bioengineering and
Nanotechnology (AIBN) / School of Chemistry &
Molecular Biosciences
Advanced Water Management Centre
Dr Phil Bond
Dr Liu Ye
Professor Zhiguo Yuan
Dr Bernadino Virdis
Dr Damien Batstone
Dr Jelena Radjenovic
Dr Maria Jose Farre
Dr Jens Kroemer
Cook Australia Pty Ltd
Page No.
4
5
6
7
8
9
10
QAAFI
Dr Ala Lew-Tabor
Dr Manuel Rodriguez Valle
Dr Jess Morgan
Dr Neena Mitter
Queensland Alliance for Agriculture & Food
Innovation (Centre for Animal Science)
11
Queensland Alliance for Agricultural and Food
Innovation (QAAFI)
12
Sirromet Wines
Ms Jessica Ferguson
Mr Adam Chapman
Dr Linda Lua
Sirromet Wines
13
Australian Institute for Bioengineering and
Nanotechnology (AIBN)
School of Chemistry & Molecular Biosciences
14
Associate Professor Craig Williams
Group Name and Contributors
Centre for Nutrition and Food Sciences
Dr Eugeni Roura
Dr Nadia de Jager
Diamantina Institute for Cancer, Immunology
& Metabolic Medicine
Professor Ranjeny Thomas
Dr Raymond Steptoe
Mater Medical Research Institute
Dr David Munster
Dr Kristen Radford
Polymer Chemistry Group
Professor Andrew Whittaker
GROUP PROFILES
Organisation/Business Unit
Centre for Nutrition and Food Sciences
(CNAFS)
Diamantina Institute for Cancer, Immunology &
Metabolic Medicine
15
Page No.
16
17
Mater Medical Research Institute (MMRI)
18-19
Centre for Magnetic Resonance
Australian Institute for Bioengineering and
Nanotechnology (AIBN)
20
Professor Matt Trau
Dr Ashley Connolly
Professor Matt Trau
Dr Muhammad Shiddiky
Australian Institute for Bioengineering and
Nanotechnology (AIBN) / School of Chemistry &
Molecular Biosciences
Australian Institute for Bioengineering and
Nanotechnology (AIBN) / School of Chemistry &
Molecular Biosciences
INDIVIDUAL CONTRIBUTORS
Organisation/Business Unit
School of Biological Sciences
Centre for Marine Studies
Centre for Integrative Legume Research
School of Chemistry & Molecular Biosciences
School of Biological Sciences
Centre for Organic Photonics & Electronics
(School of Chemistry & Molecular Biosciences)
Professor Rob Capon
Institute for Molecular Bioscience
Professor Bernie Carroll
School of Chemistry & Molecular Biosciences
Dr Marina Chavchich
Australian Army Malaria Institute
Professor David Craik
Institute for Molecular Bioscience
Professor James De Voss
School of Chemistry & Molecular Biosciences
Dr Annette Dexter
Australian Institute for Bioengineering &
Nanotechnology (AIBN)
Associate Professor Paul Ebert
School of Biological Sciences
School of Chemistry & Molecular Biosciences
Dr Darryl Eyles
Queensland Brain Institute
Professor David Fairlie
Institute for Molecular Bioscience
Associate Professor Camile Farah
School of Dentistry / UQ Centre for Cancer
Research
Associate Professor Vito Ferro
Deputy Director, Biotechnology Program
School of Chemistry & Molecular Biosciences
Dr Donald Gardiner
CSIRO Plant Industry/Queensland BioScience
Precinct, UQ-St. Lucia Campus
Professor Ian Gentle
School of Chemistry & Molecular Biosciences
ARC Centre for Functional Nanomaterials
Professor Robert G Gilbert
Centre for Nutrition & Food Sciences
School of Chemistry & Molecular Biosciences
Professor Elizabeth Gillam
School of Chemistry & Molecular Biosciences
Professor Jeff Gorman
Queensland Institute of Medical Research (QIMR)
Professor Peter Gresshoff
Centre for Integrative Legume Research
Dr Ulrike Kappler
School of Chemistry & Molecular Biosciences
Professor Mark Kendall
Australian Institute for Bioengineering &
Dr Simon Corrie
Nanotechnology (AIBN)
Professor Alexander Khromykh
School of Chemistry & Molecular Biosciences
Professor Glenn King
Institute for Molecular Bioscience
Professor Bostjan Kobe
School of Chemistry & Molecular Biosciences
Dr Shih-Chun Lo (Lawrence)
Centre for Organic Photonics & Electronics
School of Chemistry & Molecular Biosciences
Dr Patricia Lopez-Sanchez
Centre for Nutrition and Food Science
ARC Centre for Excellence in Plant Cell Walls
Professor Alan E. Mark
School of Chemistry & Molecular Biosciences
Professor Daniel Markovich
School of Biomedical Sciences
Associate Professor Fred Meunier
Queensland Brain Institute / School of Biomedical
Sciences
Associate Professor Chamindie Punyadeera
School of Biomedical Sciences
Institute of Health and Biomedical Innovations
Individual Contributors
Dr Sassan Asgari
Dr Andrew C. Barnes
Dr Christine Beveridge
Associate Professor Joanne Blanchfield
Professor Jimmy Botella
Professor Paul Burn
21
22
Page No.
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
Dr Steven Reid
Associate Professor Joe Rothnagel
Associate Professor Mark Schembri
Dr Horst Joachim Schirra
Dr Benjamin Schulz
Associate Professor Conrad Sernia
Dr Yasmina Sultanbawa
Dr Kate Stacey
Dr Matt Sweet
Professor Stephen Taylor
Dr Hang Ta
Dr Simon Worrall
Professor Paul Young
Dr Adrian WIegmans
Queensland University of Technology
Deputy Director, Biotechnology Program
School of Chemistry & Molecular Biosciences
Group Leader AIBN
School of Chemistry & Molecular Biosciences
School of Chemistry & Molecular Biosciences
School of Chemistry & Molecular Biosciences
School of Chemistry & Molecular Biosciences
School of Biomedical Sciences
Queensland Alliance for Agriculture and Food
Innovation (QAAFI)
School of Chemistry & Molecular Biosciences
Institute for Molecular Bioscience
School of Biomedical Sciences
Australian Institute for Bioengineering &
Nanotechnology (AIBN)
School of Chemistry & Molecular Biosciences
School of Chemistry & Molecular Biosciences
Queensland Institute of Medical Research (QIMR)
57
58
59
60
61
62
63
64
65
66
67
68
69
70
Dr Stefano Freguia
Centre for Microbial Electrosynthesis
Advanced Water Management Centre
71
Professor Richard Lewis
Chemistry and Structural Biology Division
Centre for Pain Research
72
Dr Zyta Ziora
Institute for Molecular Bioscience
73
QUEENSLAND ALLIANCE FOR AGRICULTURE AND FOOD INNOVATION (QAAFI)
Dr Femi Akinsanmi/A.Prof. Andre Drenth
Dr Femi Akinsanmi
Dr Femi Akinsanmi/Dr Bruce Topp
Dr Karine Chenu
Associate Professor Ralf Dietzgen
Dr Paul Scott
Professor Peter Gresshoff
Associate Professor Ralf Dietzgen
Dr Andrew Geering
Professor John Thomas
Dr Jim Hanan
Associate Professor Elizabeth Aitken
Dr Lee Hickey
Associate Professor Athol Klieve
Dr Justin Gibson
Dr Mary Fletcher
Dr Manuel Rodriguez Valle
Dr Ala Lew-Tabor
Dr Manuel Rodriguez Valle
QAAFI
(Ecosciences Precinct, Boggo Road, Dutton Park)
QAAFI
(Ecosciences Precinct, Boggo Road, Dutton Park)
QAAFI
(Ecosciences Precinct, Boggo Road, Dutton Park)
QAAFI (Toowoomba-Gatton)
CILR, John Hines Building and QAAFI, Ritchie Bldg,
UQ St Lucia Campus
75
QAAFI
Ritchie Laboratories, St. Lucia Campus
QAAFI
(Ecosciences Precinct, Boggo Road, Dutton Park)
80
Biological Information Technology Group
School of Agriculture and Food Sciences St Lucia
campus, The University of Queensland
BAgSc MRurSc PhD MASM, UQ Gatton campus or
ESP, Dutton Park
BVSc PhD
Health and Food Sciences Precinct,
Coopers Plains
Queensland Alliance for Agriculture and Food
Innovation (QAAFI)/UQ, St Lucia.
Queensland Alliance for Agriculture and Food
Innovation (QAAFI)/UQ, St Lucia.
82
83
76
77
78
79
81
84
85
86
87
Dr Sushil Dhital
Queensland Alliance for Agriculture and Food
Innovation (QAAFI)/UQ, St Lucia.
88
SCMB Biotechnology Research Projects 2016 | Industry Project
INDUSTRY PROJECTS
Would you like to undertake part of your research project in a company outside UQ?
Experience a commercial workplace
•
•
Make contacts to help you with your career
Receive support and guidance from UQ as well as your industry supervisor
Opportunities exist in these industries and more:
• biotechnology
• chemical
• pharmaceutical
• food processing
• pathology
As a Biotechnology, Chemistry or Molecular Biosciences student, you may be able to undertake a research
project or internship with companies with whom SCMB already has a working relationship. In addition, if
there is a particular company you would like to work with, you are welcome to propose it to us.
In 2014, SCMB students have been hosts for a variety of industry projects at the following companies:
•
•
•
•
•
•
•
Anteo Diagnostics
Patheon Biologics
Mars Petcare (Albury-Wodonga)
Ellume
Olayan (Saudi Arabia)
QFAB
Cook Medical
1
SCMB Biotechnology Research Projects 2016 | Industry Project
Summer project benefits student and Biotechnology company
Van Mai was inspired by a lecture i n t h e b i o t e c h n o l o g y p r o g r a m , to do an
industry placement internship that led to her work being incorporated into
presentations to customers by a successful Brisbane biotech company.
“Two scientists from Anteo Diagnostics gave a guest lecture in the second year
Issues in Biotechnology course I was taking,” she said. “I found it very interesting
and thought provoking.” Course coordinator, Associate Professor Vito Ferro,
mentioned to students that an eight-week internship at Anteo was available for a student taking the
course Biotechnology Industry Placement over the summer semester. Van applied and was chosen.
After two weeks of on-site training about company policy, equipment use, experiment design and
record-keeping, Van felt well-equipped to undertake six weeks in the company laboratory.
“I worked with one of Anteo’s signature products, Mix&Go, a high performance substance for surface
coating,” said Van.
“The product enables fragile biomolecules to correctly orientate and attach to a wide range of
surfaces. “Specifically, I worked on optimising protocols for plate-based enzyme linked immunosorbent
assays.”
Shaun Cooper of Anteo Diagnostics supervised Van’s project and said that Van was
asked to use the underlying theory of Anteo’s novel ligand-metal coordination
chemistry to determine its utility in improving sensitivity of an immunoassay in a
format were low surface area traditionally limits performance.
“Van identified the performance differences of the product in high and low surface
area plate formats,” he said. “Her data demonstrated that sensitivity differences can
be observed with the application of Mix&Go and that improvements are greater in the
lower surface area format.
“Some of her data was incorporated into technology overview presentations given by the company’s chief
scientific officer to prospective customers and partners.”
Van said that the work environment at Anteo was warm and welcoming and that the experience had taught
her about the business side of scientific research, including policy, protocols and the importance of
discussion and collaboration. “It has also built my confidence,” she said. Van is an international student
who won a scholarship from the Vietnamese government to study in Australia. She was awarded Dean’s
Commendations for high achievement in her undergraduate studies, worked as a peer tutor and charity
volunteer, and is now completing her Honours year in materials chemistry. She praised the quality of UQ’s
teaching and learning, the range of courses, lab facilities and the beautiful St Lucia campus.
Anteo Diagnostics has hosted a number of UQ biotechnology students and is keen to host more. “Students
who undertake internships like Van’s gain not only general workplace skills, but also some insight into how
Australian research contributes to commercial product realisation,” said Mr Cooper. “Support for
translational research is currently a topic of government policy debate, and projects like Van’s are a good
example of the interface between research and commercialisation.
2
SCMB Biotechnology Research Projects 2016 | Industry Project
3
SCMB Biotechnology Research Projects 2016 | Industry Project
PROFESSOR ROSS BARNARD
Director, Biotechnology Program
School of Chemistry & Molecular Biosciences
Phone: 07 3365 4612
Email: [email protected]
Teaching and other interests:
•Biotechnology Program Director
•PhD and Honours supervisor
•Real-time PCR, Infectious disease diagnosis, Antibody engineering
General Research Outline
•Development of novel diagnostic technologies.
•Antibody engineering/phage display/for cancer therapy or infectious disease diagnostics.
Current research projects
1.Infectious disease diagnostic development with a focus on Campylobacter, Flaviviruses and banana
viruses
2.Novel real-time PCR detection technology.
3.Antibody engineering for infectious disease diagnosis and cancer treatment.
4.Project 4 – Anti-inflammatory effects of transdermal metal ion absorption.
My current research projects involve collaboration with:
• Project 1 – Department of Fisheries and Forestry/QAAFI.
• Project 3 – UQ Mater Institute and Pharmacy Australia Centre of Excellence
• Project 4 – Therapeutics Research Unit, UQ Department of Medicine, Princess Alexandra Hospital
Selected Recent Publications:
Lai, R., Liang, F., Pearson,D., Barnett, G., Whiley, D., Sloots, T., Barnard, R.T., Corrie, S.R. (2012) PrimRglo:
a multiplexable quantitative real time PCR system for nucleic acid detection. Analytical Biochemistry
doi:10.1016/j.ab.2011.12.038
Luke R. Le Grand, Michaela White, Evan B. Siegel, and Ross T. Barnard (2012)
Recombinant Vaccines: Development, Production, and Application. In: Kayser, O., Warzecha, H. eds.
Pharmaceutical Biotechnology 2nd ed. Wiley-Blackwell.
Barnard, R.T., Hall, R.A. & Gould E.A. (2011) Expecting the unexpected: nucleic acid-based diagnosis and
discovery of emerging viruses. Expert Rev. Mol. Diagn. 11(4) 409-423
Barnard, R.T. (2010) Recombinant Vaccines Expert Rev.Vaccines 9(5), 461–463
Macdonald, J., Poidinger, M., Mackenzie, J.S., Russell, R.C., Doggett, S., Broom, A.K., Phillips, D., Potamski, J.,Gard, G.,
Whelan, P., Weir, R., Young, P.R., Gendle, D., Maher, S., Barnard, R.T. & Hall, R.A. (2010) Molecular
phylogeny of Edge Hill Virus supports its position in the Yellow Fever Virus group and identifies a new genetic variant.
Evolutionary Bioinformatics 6, 91-96
Liang, F., Lai, R., Arora, N., Zhang, K.L., Yeh , C-C., Graeme R. Barnett, G.R., Voigt, P., Corrie, S.R., Barnard, R.T. (2013)
Multiplex–microsphere–quantitative polymerase chain reaction: Nucleic acid amplification and detection on
microspheres. Analytical Biochemistry 432, 23–30.
Chandrasekaran, N.C., Weir, C., Alfraji, S., Grice, J., Roberts, M.S. & Barnard, R.T. (2014) Effects of magnesium
deficiency-more than skin deep. Exp. Biol. Med. Doi:10.1177/1535370214537745
4
SCMB Biotechnology Research Projects 2016 | Industry Project
PROFESSOR PETER GRAY
Australian Institute for Bioengineering and Nanotechnology (AIBN)
Phone: 07 3346 3899
Email: [email protected]
Biopharmaceuticals and mammalian cell culture based biotechnology
The acceptance of biopharmaceuticals as human therapeutics has been rapid, with global sales of such
products now exceeding $US100 billion per annum. These sales are now growing at over 20% per annum,
and there are many new biopharmaceuticals making up the potential product ‘pipelines’ of biotech and
pharma companies. Of particular note is the rapid acceptance of human and humanised monoclonal
antibodies as therapeutic agents.
Antibodies, and the majority of other biopharmaceuticals, are large complex proteins that have to be
produced by mammalian cell culture in order to have the correct post-translational modification they
require for full biological activity.
The Gray Lab is focused on engineering mammalian cells in order to improve their efficiency and utility in
the production of complex proteins. The approaches used to gain greater understanding of such systems
are also being applied to even more complex cells, viz the development of bioprocesses based on
embryonic stem cells.
Many of our research projects are collaborative, and often involve interactions with international biotech
and pharma companies.
Examples of available projects are:
1. Developing transient protein expression systems which will allow researchers to rapidly produce larger
amounts of protein needed for initial characterisation and testing.
2. Developing high throughput approaches which allow the rapid selection of clones which stably express
high levels of the desired biopharmaceutical.
3. Using modern ‘omics’ approaches to gain better understanding of cellular metabolism which will allow
maximal protein expression by mammalian cell cultures.
4. Development of novel therapeutic antibodies. A drug discovery program in this area aims to develop
novel therapeutic monoclonal antibodies for infectious diseases. The drugs will be used for treatment of
severe infections caused by antibiotic resistant bacteria. The discovery program aims to create antibody
molecules that can be engineered for targeted delivery of polymer-based nanoparticles as well as other
novel drugs.
5
SCMB Biotechnology Research Projects 2016 | Industry Project
PROFESSOR PEER SCHENK
School of Biological Sciences
Phone: 07 3365 8817
Email: [email protected]
Plant and Microbial Biotechnology, Plant-Microbe Interactions, Functional Genomics &
MetaTranscriptomics, Sustainable Biofuel Production. Microalgae Biotechnology
The Plant-Microbe Interaction Group specialises in the discovery of interesting new genes from plants and
microorganisms (www.plantsandmicrobes.com; www.algaebiotech.org)
Disease resistant plants: We use a Functional Genomics and Biodiscovery approach to study beneficial and
parasitic interactions of plants with microbes. Arabidopsis is used as a model plant to study signalling
pathways that enable plants to withstand pathogen attack or severe drought. The up- or down-regulation
of specific key regulatory genes has led to disease resistance and drought tolerance, and this strategy is
used to improve crop species.
Microbial communities associated with plants: We are using molecular profiling tools, such as functional
gene microarrays and 454 sequencing, to characterise highly diverse microbial communities that are
associated with plants to identify novel compounds for pharmaceutical and agricultural applications. This
environmental transcriptomics (metatranscriptomics) approach captures microbial activity profiles with
direct implications for crop cultivation (e.g. soil-borne diseases, greenhouse gas emmissions, yield increase
or decline).
Biofuel production from algae: We use microalgae strains that are highly efficient producers of hydrogen or
biodiesel and further optimise these by using cutting-edge molecular biology and engineering tools.
Microalgae are likely the only renewable source of fuel that could match our current and future demand
without competing for arable land and food production. Recently, we have developed large-scale
microalgae cultivation systems to produce biofuels (biodiesel), protein-rich animal feed and Omega-3 fatty
acids. This project is receiving a lot of interest from industry
Projects:
1. Increased disease resistance in plants
2. Plant cell signalling in response to beneficial microbes and plant pathogens
3. Metatranscriptomics of highly diverse microbial communities
4. Biodiesel, omega-3 fatty acids and animal feed from microalgae
Selected Recent Publications:
1. Çevik et al. (2012) MED25 acts as an integrative hub for the regulation of jasmonate-responsive gene
expression in Arabidopsis. Plant Physiology doi: http://dx.doi.org/10.1104/pp.112.202697
2. Adarme-Vega et al. (2012) Microalgal biofactories: A promising approach towards sustainable omega-3
fatty acid production. Microbial Cell Factories 11:96.
3. Lim et al. (2012) Isolation and evaluation of oil-producing microalgae from subtropical coastal and
brackish waters. PLoS ONE 7:e40751
4. Schenk et al. (2011) Unravelling plant-microbe interactions: can multi-species transcriptomics help?
Trends in Biotechnology 30:177-184
6
SCMB Biotechnology Research Projects 2016 | Industry Project
PROFESSOR ISTVAN TOTH
School of Chemistry & Molecular Biosciences
Phone: 07 3346 9892
Email: [email protected]
Drug and Vaccine Delivery:
Many peptides have been identified as potential new drugs or vaccines, but few have progressed into the
clinic. This is predominantly due to their rapid enzymatic breakdown, problematic delivery, and/or poor
inherent immunogenicity. There is a strong need for new delivery systems that overcome these issues.
Project One: Lipid-Core Peptide (LCP) delivery systems:
We have previously developed a lipid-core peptide delivery system that is applicable to the delivery of a
wide range of peptides. The LCP system can be optimized to improve the absorption and stability of the
peptide. An advantage of the LCP system for vaccine delivery is that the antigen, carrier, and adjuvant can
be included in a single chimeric molecule. Models under investigation for the use of the LCP system include
vaccines against malaria, hookworm, group A streptococcus, and cancer. Further structure-activity studies
are required to optimize the delivery system and to identify the mechanism of action of the delivered
peptides on the host immune response.
Aim: to perform structure-activity studies to further optimize the LCP delivery system.
Project Two: Chemo-enzymatic synthesis of drug/vaccine delivery systems:
This project aims to address shortcomings in peptide delivery by coupling naturally occurring sugars and
lipids to the peptides of interest using a combination of organic synthesis and enzymatic transformations.
This multidisciplinary approach (chemistry, biotechnology, biology) has the potential to not only improve
peptide absorption and metabolic stability, but to enhance the access of peptides to target sites using
carbohydrate and/or amino acid transport systems. The combination of chemical and enzymatic synthesis
provides access to complex carbohydrate structures that can be used to target drug molecules. One
example is the use of glycosyltransferases from Neisseria meningitidis to target Leu-enkephalin peptide
derivatives (potential pain drug candidates) to opioid receptors in the central nervous system.
Aim: to design and develop a generally applicable, novel drug delivery system (synthesized chemically and
chemo-enzymatically) that targets specific cell types.
Project Three: Nanovaccine delivery systems:
Recent developments in nanomedicine/vaccinology have identified that the size and morphological
characteristics of nanoparticle vaccines affect their efficacy. Preliminary investigations have demonstrated
that 20 nm nanoparticles displaying peptide epitopes on their surface were able to induce very strong
immune responses against those epitopes. We have also shown that this response was size dependent. This
project aims to further explore the effect of size and morphology on the efficacy of nanoparticle vaccines.
Aims: 1) Produce and self-assemble multi-epitope vaccine constructs. 2) Fully characterize nanoparticles,
including arrangement of the epitopes on the surface.
7
SCMB Biotechnology Research Projects 2016 | Industry Project
PROFESSOR MATT TRAU
Australian Institute for Bioengineering and Nanotechnology (AIBN)
Phone: 07 3346 4173
Email: [email protected]
Our Centre for Biomarker Research and Development is located in the Australian Institute for
Bioengineering and Nanotechnology (AIBN) and has access to state-of-the-art chemistry synthesis, and
characterisation facilities. Students working in the Centre will have the opportunity to create nanoscaled
biosensors for applications in cancer, infectious disease, therapeutics and point-of-care devices. Students
will also be given the opportunity to work with leading geneticists, epigeneticists and clinical researchers to
test these devices in clinical settings. The Centre has a focus on developing diagnostic devices for early
detection of diseases such as cancer, when it is most responsive to treatment which also provides the
greatest social and economic benefits to society. Nanotechnology offers the promise of miniaturized,
inexpensive, flexible and robust “plug-and-play” molecular reading systems which can be effectively
deployed to detect diseases in a clinical setting. Current projects available include:
1) Microfluidic Devices for Capturing Rare Circulating Tumour Cells
The progression of cancer in patients is characterized by cells that invade locally and travel through the
blood stream to metastasize in the other parts of the body. These cells, account for 1 or fewer cells in 106
blood cells and are known as circulating tumour cells (CTCs). Development of advanced technologies for
capturing CTCs in blood in the early stage of the metastasis process would transform the treatment of
cancer. This project strives to build and test a microfluidic device to enable selective capture and detection
of CTCs using threedimensional microstructured electrodes within the the device.
2) Nanodevices/Nanobiosensors for Cancer Biomarker Proteins
Detecting low concentrations biomarkers in serum is potentially useful for the diagnosis and prognosis of a
disease. The development of a detection method that is rapid and cheap could revolutionize the treatment
of diseases such as cancer. In this project, we aim to fabricate nanobiosensors with nanostructured
3D-electrodes to detect single protein molecules in blood. Students will achieve hands on experience in the
design, fabrication and application of the microfluidic devices and electrochemical micro(nano)biosensors.
3) DNA Nanomachinery for Early Breast Cancer Detection
Subsets of non-coding (nc) RNAs serve as potential biomarkers of diseases. This project involves designing,
developing and evaluating novel DNA nanomachinery to perform tasks that are currently beyond the reach
of existing molecular readout technologies. We aim to use these nanomachines as a new technology
platform to rapidly detect ncRNA biomarkers in breast cancer patients. This interdisciplinary project will
provide an opportunity for students to acquire diverse skills in chemistry, molecular biology and
bioengineering.
4) Point-of-Care Diagnostics
Point-of-care (POC) diagnostics have the potential to revolutionise global health care by enabling diseases
to be rapidly diagnosed ‘on the spot’ using minimal specialised infrastructure. POC devices need to be
highly sensitive, specific, practical, cost effective and portable if they are to be used in resource limited
settings. We are focused on novel and simple (nanotechnology-based) molecular assays to generate new
POC diagnostic technologies. Students will be involved in designing, developing and evaluating methods to
rapidly detect pathogenic DNA using devices such as mobile telephones. This interdisciplinary project will
provide an opportunity to acquire diverse skills in chemistry, molecular biology, bioengineering, and
biotechnology.
8
SCMB Biotechnology Research Projects 2016 | Industry Project
2. Turning emissions into fuels using electricityboosted fermentation. / Dr Jens Kroemer
Microbial electrosynthesis is a cutting edge
technology to produce valuable products from
oxidised carbon sources. This study will apply
bioelectrochemical systems to boost the bioproduction of fermentation products by
Clostridia.
THE ADVANCED
WATER MANAGEMENT
CENTRE (AWMC)
Honours Projects at The Advanced Water
Management Centre (AWMC)
Students with interests in environmental
microbiology/biotechnology,
wastewater
treatment processes, environmental chemistry,
microbial ecology and function, and/or
application of molecular approaches, are
encouraged to apply for Honours projects listed
here. The AWMC is an international centre of
excellence for innovative wastewater technology
and management, with over 15 Research
Academics and more than 50 graduate students
(see http://www.awmc.uq.edu.au/). If you are
motivated by our exciting science and interested
in honours projects or higher degrees then please
get in contact with either Dr Phil Bond,
[email protected]; or directly contact
the academics listed with the project descriptions
below. For Honours students that qualify at the
AWMC a tax free stipend of $3000 can be
available (subject to the project).
3. 1,3 propanediol production from glycerol
using microbial electrosynthesis with Citrobacter
ssp. / Dr Jens Kroemer
Microbial electrosynthesis is a cutting edge
technology to produce valuable products from
oxidised carbon sources. This study will explore
the production of 1,3 propanediol from glycerol
in a engineering Citrobacter species. The project
is a collaboration between the Centre fro
Microbial Electrosynthesis at UQ and the
University of Ghent in Belgium.
4. Determining the microbes that are eating our
sewer pipes. / Dr Guangming Jiang, Dr Phil Bond
and Prof Jurg Keller
Certain microorganisms cause massive problems
in sewers by forming biofilms on the concrete
and producing sulfuric acid that corrodes the
concrete pipes. This project will investigate the
molecular ecology and microbial activities to
understand the effects of treatments aimed to
mitigate this problem.
Research Interests and Graduate Research
Projects
Our research focuses on wastewater treatments
systems, polluted environments, production of
energy from waste, ocean biogeochemistry,
water recycling and solid waste treatment. Below
are examples of research topics available as
Honours projects at the AWMC; further projects
are available within the centre, please enquire.
5. Influence of soluble organics on struvite
crystallization. / Dr Chirag Mehta and Dr.
Damien Batstone
Struvite crystallization technology is being widely
applied in full-scale to remove phosphorus from
wastewater. This project will investigate
influence of soluble organics on struvite crystal
formation through solubility, growth rate,
product size distribution, and product quality
measurements.
1. Determining the mechanism of free nitrous
acid inhibition on biofilm activity of wastewater
microorganisms. / Dr Chris Lu Fan, Dr Phil Bond
and Prof Zhiguo Yuan
There is great interest in disruption or
destruction of problem microbial biofilms. This
project will investigate the disruptive effect of a
toxin, nitrous acid, on microorganisms relevant to
wastewater treatment biofilms, with the aim to
determine
molecular
and
physiological
understanding of the toxic effect.
6. Binders for struvite granulation. / Dr Chirag
Mehta and Dr. Damien Batstone
There is great interest to formulate and test
waste derived fertilizer product (struvite). This
study will investigate role of different binders on
mechanical and agronomic properties of the
granulated product
9
SCMB Biotechnology Research Projects 2016 | Industry Project
COOK AUSTRALIA PTY LTD
Address: 12 Electronics Street, Eight Mile Plains QLD 4113
Phone: 07 3365 4612
Email: [email protected]
A range of possible projects is available. Applicants for this project should contact Prof Ross Barnard in the
first instance.
Cooks contribution:
Cook will provide project supervision and ongoing advice.
10
SCMB Biotechnology Research Projects 2016 | Industry Project
QUEENSLAND ALLIANCE FOR AGRICULTURE &
FOOD INNOVATION (Centre for Animal Science)
DAFF Biotechnology Laboratory, Level 3, Building 80, UQ-St Lucia Campus
Phone: 07 3255 4535 or 07 3255 4529 or 07 3255 4527
Website: http://www.qaafi.uq.edu.au/cas
(Left) Dr Manuel Rodriguez Valle: Molecular
Parasitologist and Molecular Immunologist
(Middle) Dr Ala Lew-Tabor: Molecular Biologist
(Right) Dr Jess Morgan: Molecular
Parasitologist
Applied Animal Disease Biotechnology Research Opportunities:
There are options for Honours, Masters or PhD
are difficult to distinguish morphologically. DNA-based
research with the group. It is an opportunity to obtain
diagnostic technology has been developed to
industry or animal health research experience.
distinguish the seven species. Current research is
investigating if genetic markers can be used to
Project 1: Cattle tick vaccine research – Drs Ala Lewdistinguish different populations within species. DNATabor and Manuel Rodriguez Valle-Rhipicephalus
based technologies in use include traditional and next
(Boophilus) microplus, or the cattle tick, has a high
generation DNA sequencing, real-time PCR, SNP
impact on the cattle industry, costing Australia $175m
analysis and microsatellite screening.
per annum. The aim of the research is to identify tick
vaccine candidates and produce novel vaccine
Project 4: Bovine genital campylobacteriosis - Dr Ala
candidate antigens using yeast expression systems.
Lew-Tabor. - BGC is reproductive disease of cattle
Research programs can be developed to include gene
which is difficult to diagnose. Research includes
cloning, yeast expression, development of novel
subspecies the development of novel assays (real time
hybrid molecules (to enhance immune protection),
PCR and high resolution melt methods) to distinguish
and protein purification and analysis. Research also
the causative pathogen Campylobacter fetus subsp
includes the study of tick protein biological function
venerealis from closely related Campylobacter spp.
during host:parasite interactions.
Project 5: Tick fever diagnostics and vaccine
development - Drs Ala Lew-Tabor, Jess Morgan and
Project 2: Paralysis tick vaccine research – Dr Manuel
Manuel Rodriguez Valle - Tick fever is caused by
Rodriguez Valle - Ixodes holocyclus (paralysis tick)
protozoan parasites Babesia bovis and B. bigemina
causes fatal paralysis in companion animals and
and the rickettsia Anaplasma marginale. These
livestock, with approximately 100,000 toxicoses cases
pathogens are transmitted by the cattle tick
reported along the east coast of Australia annually.
(Rhipicephalus microplus) and can cause fatal disease
Research to develop a protective vaccine has recently
in cattle in northern Australia. These diseases are
commenced with good opportunities for research
currently managed through the implementation of a
students. Research can include: bioinformatics to
live vaccine program (Department of Agriculture,
study next gen transcriptomic data, expression
Fisheries & Forestry). Together with DAFF, CAS
analysis, vaccine antigen construction (including
scientists are developing improved methods to
hybrid molecule construction to enhance immune
differentiate vaccine and field isolates (real time PCR
protection), yeast display library screening, immune
and high resolution melt methods), as well as novel
screening, toxicity screening using tissue and
safe vaccine delivery systems.
laboratory animals, and the study of tick protein
biological function during host:parasite interactions.
Project 3: Eimeria diagnostics - Dr Jess Morgan Coccidiosis of chickens is an economically important
disease caused by infection with species of Eimeria.
Seven recognised species occur in Australia but they
11
SCMB Biotechnology Research Projects 2016 | Industry Project
DR NEENA MITTER
QUEENSLAND ALLIANCE FOR AGRICULTURE AND FOOD INNOVATION (QAAFI)
Queensland Agricultural Biotechnology Centre (QABC), St. Lucia Campus
Phone: 07 3346 6513
Email: [email protected]
Website: http://www.qaafi.uq.edu.au/
Project 1: RNA silencing based resistance to fungal diseases
RNA silencing has proven to be an emerging strategy to control plant viruses and nematodes in agricultural
crops. Transgene- mediated virus resistance is a classical example of RNA silencing and its role in antiviral
defence in plants. There have been many examples of transgene mediated resistance using viral sense,
antisense or inverted repeat sequences for targeting RNA viruses, DNA viruses and viroids. In fungi, RNA
silencing phenomenon was called Quelling when first described in Neurospora crassa in 1992. This
technology of transgene induced RNA silencing can be exploited to control fungal diseases of economic
importance. The project will involve elucidation of the mechanism of RNA silencing based host delivered
resistance against fungi.
Project 2: Artificial MicroRNA-Mediated Virus Resistance in Plants
RNA silencing in plants is a natural defense system against foreign genetic elements including viruses. This
natural antiviral mechanism has been adopted to develop virus-resistant plants through expression of virus
derived double-stranded RNAs or hairpin RNAs, which in turn are processed into small interfering RNAs
(siRNAs) by the host’s RNA silencing machinery. While these virus-specific siRNAs were shown to be a
hallmark of the acquired virus resistance, the functionality of another set of the RNA silencing-related small
RNAs, microRNAs (miRNAs), in engineering plant virus resistance has not been extensively explored. The
biogenesis of mature miRNAs is not affected if few nucleotides are changed in the mature miRNA
sequence. By replacing natural mature miRNA sequences in the precursors with the virus specific
sequences, resistance may be obtained against plant viruses. The project will involve making amiRNA
constructs targeting plant viruses and using transient and stable expression in model plants for enhanced
resistance.
Project 3: Plant based expression of viral proteins for nanoparticle based vaccine delivery
Plants (both whole plants and in vitro cultures) are gaining attention for the large-scale production of
recombinant proteins and particularly, as a promising platform for vaccine production. Some of the
advantages of the plant-based systems are that they can rapidly be bulked to large biomass, its
maintenance is relatively inexpensive, and they do not harbor mammalian proteins or pathogens. Protein
production could be achieved through stable or transient expression. The current project will investigate
plant based expression system for some of the antigens targeting veterinary diseases.
Project 4: Micro RNA expression in Avocado in relation to root initiation
Clonal propagation of commercially used cultivars is required to meet the demand of the growers for
clean and genetically uniform disease free material. Clonal propagation enables multiplication of elite
rootstocks and other identified cultivars that have desirable traits such as disease resistance and increased
yield/fruit quality, which benefits industry. Root initiation in cuttings of desired cultivars can be a major
hurdle in clonal propagation especially with reference to tree crops. MicroRNAs (miRNAs) have been found
to regulate the expression of genes essential for the various biological mechanisms in plants as well as
animals. The project will involve characterization of miRNA expression in horticultural crops like avocado to
understand the mechanism of root initiation.
12
SCMB Biotechnology Research Projects 2016 | Industry Project
JESSICA FERGUSON
ADAM CHAPMAN
SIRROMET WINERY, 850 Mt Cotton Rd, Mt Cotton Qld 4165
Phone: 07 3206 2999
Email: [email protected]
With every vintage, new challenges emerge in winemaking. Over the past 5 years Queensland vintage
weather conditions have varied enormously requiring constant vigilance and innovation by the winemaker
to maintain consistency of quality and wine style. Several emerging patterns have prompted the need for
investigation into specific wine processing issues. The following suggestions for projects are intended to
address current dilemmas in winemaking in Queensland, and have the potential to provide real solutions to
the industry. NOTE: Projects may be carried out in part, or completely, at Sirromet Wines Pty Ltd on Mt
Cotton Road, Mt Cotton. Students will need to arrange their own transport.
EXAMPLES OF POSSIBLE PROJECTS ARE:
‘Pinking’ – non desirable colour shifts in Pinot Gris and Verdelho varieties. Investigation of different wine
matrices (pH, SO2 levels, phenolics content, degree of chemical reductive environment) on Pinot Gris
colour. Investigation of pinking precursors in must and wine, investigation into must handling techniques
on precursor levels in juice and wine. Assessment of various fining methods in removing pinking precursors.
Quercetin dihydrate in red varieties, levels, weather influences (drought years versus normal). Critical levels
of quercetin dihydrate for likely precipitation from wine. Fermentation influences on quercetin
concentrations and stability. Wine matrix variables affecting stability/precipitation of quercetin dihidrate
over time. Total phenolics levels in red wines, a measure of quality? Assessment of simple empirical
determinations of phenolic groups vs accurate instrumental assays (HPLC). Correlation with expert tasting
assessments.
Are there relationships/interactions between DO2, FSO2 and DCO2 in finished wines?
Yeast population desired levels in sparkling secondary fermentations given various alcohol, protein, TSO2,
VA and phenolics levels.
Investigation of different sparkling yeast tolerance to high TSO2 levels with influences from pH, alcohol and
VA.
Resveratrol levels in Granite Belt red wines – varietal differences, significance of altitude/soil,
vintage/climate conditions, fruit condition, ripeness & canopy cover during ripening. Resveratrol levels in
grapes versus wine. Stability of resveratrol in wine over time.
Extracting red grape skins for resveratrol with a view to developing a suitable colourless extract to enrich
red wines with resveratrol without affecting wine taste, colour or mouthfeel.
N, P, K, Fe levels in juices pre-fermentation for direct sugar accumulation via yeast.
Copper additions prior to bottling – investigation into effects on protein stability and potential to cause
copper casse formation. Browning in white wines as a result of interaction between copper and excess
phenolics in white wine.
13
SCMB Biotechnology Research Projects 2016 | Industry Project
DR LINDA LUA
Protein Expression Facility
Australian Institute for Bioengineering and Nanotechnology
Phone: 07 3346 3979
Email: [email protected]
Website: www.uq.edu.au/pef
Project 1:
Mass manufacturing viral vaccines for
pandemic influenza
The ideal way to protect against pandemic flu is to
vaccinate the entire Australian population as soon as
possible after a dangerous strain starts to spread. Current
manufacturing technology, which begins by making an
infectious virus in chicken eggs, is unable to quickly deliver
a mass vaccine to the entire Australian population. Recent
scientific progress has demonstrated that it is possible to make a non-infectious “empty” virus shell (viruslike particle) inside cells. This new product is able to provide full protection against a lethal influenza
challenge, when administered nasally. Our approach relies on the expression and purification of key
influenza virus proteins, which are then processed in reactors into non-infectious virus-like particles.
Skills: Cloning, site-directed mutagenesis, bacterial protein expression, protein purification, biophysical
analysis of protein.
Project 2: High throughput parallelised protein production
Obtaining large quantities of pure proteins for structural and functional analysis remains a main bottleneck
in biological research and pharmaceutical development. As no universally applicable expression system
exists, it is often necessary to test several expression systems to achieve a desired outcome. A HTP
platform for parallelised cloning and expression in E.coli is established in our lab. Further development in
HTP expression using other eukaryotic systems (yeast, insect cell and mammalian cell) is on-going in our
lab. Skills: Cloning, protein expression in different hosts (E.coli, yeast, insect cells and mammalian cells),
protein purification, protein analysis.
Project 3: Novel protein purification technologies
Recovery of the protein of interest from a culture is just as important as obtaining the expression the
protein. The end application of the purified protein determines the level of purity and yield required.
Minimising protein lost and maximising protein purity in a simple purification process is desirable. We are
developing new purification technologies (chromatographic and non-chromatographic) to improve the
purification of different types of proteins and from different expression host systems.
Skills: Protein expression in different hosts (E.coli, yeast, insect cells and mammalian cells), protein
purification, protein analysis.
14
SCMB Biotechnology Research Projects 2016 | Industry Project
ASSOCIATE PROFESSOR
CRAIG WILLIAMS
Natural product total synthesis, isolation and associated medicinal chemistry.
Drug Design and Development / Green chemistry
Phone: 07 3365 3530
Email: [email protected]
Anti-cancer, neurodegenerative disease and insect
active limonoids: [in collaboration with Dr Paul
Savage (CSIRO), Prof. Peter Dodd (SCMB. UQ) and
A/Prof. Gimme Walter (SBS, UQ)].
Recently we achieved the total syntheses of a
number of the limonoid family members, such as,
Khayasin 1 and Cipadonoid B 2. The synthesised limonoids 1 and 2 are closely related to Gedunin 3, another
limonoid family member, which displays anti-cancer and neurodegenerative disease activity in Heat Shock
protein 90 (Hsp90) models. We would now like to investigate the total synthesis of gedunin 3, which has
yet to be reported, and explore the gedunin 3 structure against Hsp90 using state of the art medicinal
chemistry techniques.
Cubane Chemistry: A Benzene Ring Drug Isostere? [in collaboration with
Dr Paul Savage (CSIRO) and Prof. James De Voss (SCMB, UQ)]. Cubane 4,
when viewed from the corners (i.e. 5) can be considered roughly the
same size as a benzene ring (i.e. 6). This is equally true when you take into
consideration the  clouds of benzene, that is, cubane 4 is about the same
“thickness”. Therefore the 1,2- 1,3- and 1,4- substituted cubanes are similar to ortho-, meta-, and parasubstituted benzenes respectively. Furthermore, the cubane structure is actually very stable – cubane ringopening is thermally disallowed by orbital symmetry. With this in mind the project would involve replacing
the phenyl ring in a current drug molecule and comparing bioloical assay data. It would also be expected
that cubane 4 has completely different P450 metabolism profiles, which will be explored in collaboration
with Prof. James De Voss.
Discovery and Development of Novel Analgesics [in collaboration with
Prof. Maree Smith from the Centre for Integrated Preclinical Drug
Development (CIPDD)/TetraQ)]: The prevalence of painful diabetic
neuropathy (PDN) is 7% within a year of diagnosis of diabetes and 50% by
25 yrs of diabetes. The medicines currently used to treat PDN are not
effective in less than 50% of patients. Hence, we propose to develop new,
effective medicines for the alleviation of PDN by investigating the biology
(Smith lab) of unusual heterocycles (Williams lab) that deliver the
neurotransmitter molecule NO (nitric oxide).
Green Chemistry [in collaboration with Prof. Ian Gentle (SCMB, UQ)]. Organic reactions are key to new
molecules that are in ever-increasing demand for applications in the pharmaceutical, materials and
agrichemical sectors. This demand, however, places growing pressure on synthetic chemists to limit or even
eradicate environmentally unfriendly chemical waste production. Steps towards such measures are now
commonly termed “Green Chemistry”. Projects looking at developing new solvents and new surfactants are
available. Applying physical techniques [e.g. small angle scattering (SAXS), neutron scattering (SANS) and
dynamic light scattering (DLS)] to understand macromolecular mechanisms is an important part of the
work. A/Prof. Williams (ARC Future Fellow) he has held past and present multimillion dollar industry
research contracts in addition to ARC and NHMRC grants. Further projects are available on request.
15
SCMB Biotechnology Research Projects 2016 | Group Profiles
CENTRE FOR NUTRITION & FOOD SCIENCES (CNAFS)
QUEENSLAND ALLIANCE FOR AGRICULTURE AND
FOOD INNOVATION (QAAFI)
DR EUGENI ROURA (Left)
Phone: 07 3365 2526
Email: [email protected]
DR NADIA DE JAGER (Right)
Phone: 07 3365 1865
Email: [email protected]
MOLECULAR NUTRITION, METABOLISM AND TASTE
The world of taste perception and our understanding thereof is in the process of undergoing significant
expansion. Taste receptors have been uncovered as a network of nutrient sensors present not only in the
oral cavity, but also in many other parts of the body, including heart, gastrointestinal tract and brain. The
roles that these receptors play outside the mouth is not completely understood, however current findings
suggest that they are involved in the fundamental process of controlling the hunger-satiety cycle and food
intake. Our research group aims to gain a better understanding of how the taste system responds to
different nutritional paradigms. Model systems for studying common eating disorders such as obesity and
anorexia are assisting us in addressing our research questions.
Project 1: How are nutrients sensed in the gastrointestinal tract? The role of taste receptors. In order to
bridge gaps in the current understanding of how nutrients are sensed in the gastrointestinal tract, a
number of molecular and cell biology techniques will be employed. For example immunohistochemistry,
gene expression and in situ hybridisation techniques will allow for the identification and quantification of
key candidate gene expression and protein levels. A background in biomedical sciences or animal
physiology is recommended for this project.
Project 2: Knowing more about your sense of taste – applications to obesity research
Humans have 25 different types of bitter taste receptors that can detect and taste many more bitter
compounds. Our ability to sense these compounds are believed to be associated with an evolutionary
advantage for sensing and therefore avoiding potential toxic or harmful substances. Individual variation
exists at the molecular level where the genes encoding the bitter taste receptors can have mutations.
Different vegetables contain different kinds and different amounts of bitter compounds. Bitter compounds
have been shown to have a remarkable ability to elicit a “fuller for longer” feeling and is therefore relevant
to obesity research. This project will investigate mutations in bitter taste receptor genes and links with
bitter compounds commonly found in vegetables.
Project 3: Biotechnology and Food Science
Fibre is known to have wide reaching health benefits and is being consumed in increasing amounts as part
of a human diet. However, there appears to be more to the story, at least in rodents, where it was shown
that excessive consumption of dietary fibre was associated with increased susceptibility to bacterial
infections. Pigs are ideal model animals for humans and this project will investigate changes occurring in pig
tissues (already collected) as a consequence of fibre. To address this objective, modern biotechnology
techniques will be used by measuring the relative gene expression levels by real time PCR of candidate
genes associated with hunger and satiety as well as genes that serve as markers for inflammation.
16
SCMB Biotechnology Research Projects 2016 | Group Profiles
DIAMANTINA INSTITUTE FOR CANCER,
IMMUNOLOGY & METABOLIC MEDICINE
PROFESSOR RANJENY THOMAS
Arthritis Qld Chair of Rheumatology Immunology Programme
Address: Princess Alexandra Hospital, Buranda
Phone: 07 3240 5365
Email: [email protected]
Project 1: Pathogenesis of inflammatory arthritis in skg mice
Self-reactive T cells with a low signalling capacity through the T cell receptor have been observed in the SKG
mouse model of rheumatoid arthritism, and have been linked to a spontaneous mutation in the ZAP-70
signal transduction molecule. This project examines the role that antigen presenting dendritic cells play in
the development of arthritis in this model, and whether dendritic cell immunotherapy can be used to treat
arthritic mice. Suitable for: PhD, Masters or Honours.
Project 2: Human type 1 diabetes
We have developed a new diagnostic assay which identifies individuals with Type 1 diabetes (T1DM) and
some of their relatives at risk of diabetes. Exposure of blood monocytes to the bacterial product
lipopolysaccharide led to an abnormally low level of activation of the protein, RelB. We are now extending
these studies to determine the value of the assay for predicting whether otherwise healthy siblings of
children with T1DM will develop diabetes in the future. This would allow us to identify those at risk so that
they could be treated earlier or encouraged to make preventative changes to their lifestyle. This project
involves analysis of factors contributing to the abnormal RelB test, and researching ways in which RelB
function can be restored in these dendritic cells, for new treatments.
Suitable for: PhD, Masters or Honours.
DR RAYMOND J. STEPTOE
Phone: 07 3240 5393
Email: [email protected]
Project: Gene Therapy for Autoimmune Disease
Autoimmune diseases develop when the body’s immune system mistakenly attacks normal, healthy body
tissues. We are interested in developing approaches to prevent or treat autoimmune disease. Dendritic
cells are important educators of the immune system and control both immunity and tolerance to selftissues. We have demonstrated that steady-state antigen-expressing dendritic cells can turn off responses
in not only naïve T cells, but surprisingly, also in memory T cells. We are now seeking ways to apply this
knowledge to develop a vaccine-like approach to therapy of autoimmune diseases. Projects are available
that examine the basic immune biology of immune tolerance or novel methods of in vivo gene transfer that
can achieve immune tolerance.
17
SCMB Biotechnology Research Projects 2016 | Group Profiles
DR KRISTEN RADFORD
Immunotherapy Program
Mater Medical Research Institute
Phone: 07 3163 2567
Email: [email protected]
Targeting the Human Cross-priming Dendritic Cells for Immunotherapy
Background: Dendritic cells (DCs) are the key antigen presenting cells responsible for initiating and directing
immune responses. In mice there are distinct dendritic cell subsets that are specialised in the types of
immune responses they generate. However, dendritic cells are poorly understood in humans and
translation is complicated by differences in human and mouse immune systems and in particular expression
of pattern recognition receptors. We have identified a rare human DC subtype, termed CD141+ DC, that we
hypothesize plays an important role in the induction of immune responses against viruses and cancers by
their specialised ability to stimulate cytotoxic T cells. These DC are attractive targets for the design of new
vaccines against cancers and infectious diseases. This project will explore the interaction of CD141+ DC with
tumour cells and virus-infected cells and the mechanisms by which they generate cytotoxic T cell
responses.
Hypotheses: CD141+ DC are specialized in the induction of cytotoxic T cell responses and as such are
attractive vaccine targets
Specific Aims:
Project 1: To study the function of CD141+ DC and their response to pattern recognition receptors in
human tissues and in a humanized mouse model.
Project 2: To investigate the interactions of different human DC subsets with tumour cells.
Achievable outcomes:
• Training in human cellular immunology, cancer immunology and immunotherapy.
• Expertise in isolation of primary human cells, primary cell culture, flow cytometry analysis and sorting,
other immunological assays (eg cytokine ELISAs), PCR
• Expertise in a novel humanised mouse model
18
SCMB Biotechnology Research Projects 2016 | Group Profiles
MATER MEDICAL RESEARCH INSTITUTE
The Role of Inflammation and Immunity in
Gynaecological Cancer Therapy
Laboratory: Cancer Therapeutics
Supervisor/s: David Munster, Jim Coward, Kristen
Radford
Funding: Team budgets
Student Objectives
• To develop an understanding of the investigation of human cancer therapy
• To develop the ability to identify key scientific questions, to design optimal experiments to address the
questions, to efficiently carry out the experiments, to interpret the results and report the outcomes
• To learn a variety of research techniques (see below)
• To develop the ability to interact with team members and collaborators to maximise outcomes
Project Overview: Ovarian cancer patient survival is the poorest of all gynaecological cancers, due to late
diagnosis and to poorly effective therapies. Evidence is increasing that improvements in therapeutic
outcomes will require control of inflammatory mediators and appropriate stimulation of the patient’s
immune system. We have access to relatively large quantities of primary tumour material from patients
with ovarian cancer and other gynaecological malignancies. This is an important resource for research and
the development of better therapies.
Available Projects:
• Determination of inflammatory cytokines in samples from patients with gynaecological cancer
• Phenotype and functional characterization of leukocytes in samples from patients with gynaecological
cancer
• How does the gynaecological cancer microenvironment impair anti-cancer therapy?
• Testing therapies on primary human gynaecological cancers in vitro and in mice
Achievable Outcome: Generation of novel data that may lead to improved treatment of cancer
Techniques : This project will introduce the student to a range of techniques:
Cell and molecular biology methods, cellular immunology, human tissue handling, small animal
experimentation, ELISA, and flow cytometry.
Relevant Publications
1. Pearson, T. et al., Humanized SCID mouse models for biomedical research. Curr Top Microbiol Immunol.
2008;324:25-51.
2. Coward, J. et al., Interleukin-6 as a therapeutic target in human ovarian cancer. Clin Cancer Res.
2011;17(18):6083-96.
Further Information
Dr David Munster
Phone: 07 3163 2571
Email: [email protected]
19
SCMB Biotechnology Research Projects 2016 | Group Profiles
POLYMER CHEMISTRY GROUP
PROFESSOR ANDREW WHITTAKER
GROUP LEADER, Australian Institute for Bioengineering & Nanotechnology (AIBN)
Phone: 07 3346 3885
Email: [email protected]
Website: www.uq.edu.au/polymer-chemistry/
Our research group develops polymeric materials to improve human health. Our large
group of researchers have programs of research across the spectrum from bench topto-bedside. Specifically we work in the fields of sensing of disease, delivery of drugs and regeneration of
tissue. The projects listed below are all done in collaboration with experts in clinical application of
biomaterials, and will provide a solid foundation in practical and theoretical aspects of the use of polymeric
materials as biomaterials. Honours projects are available in the following areas (for project details, please
see our website or contact Andrew by email). The web site lists other projects.
1. Functionalisation of the surfaces of titanium alloys for improved osseointegration
2. Development of novel polymer scaffolds to aid the repair of the spinal cord
3. Development of low-fouling, anti-microbial surface coatings
4. Novel polymer molecular imaging agents (MRI) for early disease detection
5. Peptide hydrogels for cell delivery
20
SCMB Biotechnology Research Projects 2016 | Group Profiles
PROFESSOR MATT TRAU
DR ASHLEY CONNOLLY
Centre for Biomaker Research and Development,
Australian Institute for Bioengineering & Nanotechnology (AIBN)
School of Chemistry & Molecular Bioscience (SCMB)
Phone: 07 3346 4173(Matt) / 07 3346 4172(Ashley)
Email: [email protected] / [email protected]
1) DNA Nanomachinery for Early Breast Cancer Detection
Every 3 minutes a woman is diagnosed with breast cancer. Despite the increasing incidence of breast
cancer in the Western world, death rates have been decreasing since 1990. This is the result of treatment
advances, increased awareness and early detection. It is widely accepted that early detection results in
much higher survival rates, but it is proving difficult to detect the cancer in its early stages. Subsets of RNA
that are not translated into proteins have recently been identified in cancerous growths. These non-coding
(nc) RNAs serve as potential biomarkers of disease. Our group is designing, developing and evaluating novel
DNA nanomachinery to perform tasks that are currently beyond the reach of existing molecular readout
technologies. We aim to use these nanomachines as a new technology platform to rapidly detect ncRNA
biomarkers in breast cancer patients.
This interdisciplinary project combines the latest developments in molecular genetics with cutting edge
nanobiotechnology and will provide an opportunity for students to acquire diverse skills in chemistry,
molecular biology and bioengineering.
2) Point-of-Care Diagnostics
Point-of-care (POC) diagnostics have the potential to revolutionise global health care by enabling diseases
to be rapidly diagnosed ‘on the spot’ using assays that require minimal specialised infrastructure. The
simplicity of POC assays enables them to be performed by health care workers or even the patient, which
enables rapid diagnosis of a disease. This improves the time taken to treat a disease, leading to better
patient care and a reduced rate of mortality and morbidity. POC devices need to be practical, cost effective
and portable with high sensitivity and specificity if they are to be used in resource limited settings.
Within our Centre we have an ongoing research program focused on designing and building simple
(nanotechnology-based) molecular assays to generate new POC diagnostic technologies. This Honours
project will be involved in designing, developing and evaluating novel methods to rapidly amplify and
ultimately detect pathogenic DNA and RNA using everyday devices such as mobile telephones.
This interdisciplinary project combines the latest developments in biological chemistry with cutting edge
nanobiotechnology and will provide an opportunity to acquire diverse skills in chemistry, molecular biology,
bioengineering, and biotechnology.
21
SCMB Biotechnology Research Projects 2016 | Group Profiles
PROFESSOR MATT TRAU
DR MUHAMMAD SHIDDIKY
Centre for Biomarker Research and Development,
Australian Institute for Bioengineering & Nanotechnology (AIBN)
School of Chemistry & Molecular Bioscience (SCMB)
Phone: 07 3346 4173 (Matt) or 07 3346 4169 (Muhammad)
Email: [email protected] / [email protected]
1) Microfluidic Devices for Capturing Rare Circulating Tumour Cells
As cancer mortality rates continue to rise, the national impact of the cancers is beginning to overwhelm
healthcare services. The progression of cancer in patients is characterized by cells that invade locally and
metastasize to nearby tissues or travel through the blood stream to set up colonies in the other parts of the
body. These cells, accounting for 1 or fewer cells in 105 – 106 peripheral blood mononuclear cells, are
known as circulating tumour cells (CTCs). Development of advanced technology for capturing CTCs in blood
in the early stage of the metastasis process would be transformative in the treatment of cancer. This
project strives to build and test a microfluidic device with the capacity to enable selective capture and
sensitive detection of CTCs by incorporating three-dimensional microstructured electrodes within the
detection/capture domain of the device.
2) Nanodevices/Nanobiosensors for Cancer Biomarker Proteins
The clinical use of immunoassays in treatment of cancer at early stages of the disease requires detection of
proteins of typically 10-16 to 10-12 M concentration in whole blood, blood plasma or serum samples.
Detecting this low concentration of proteins is potentially useful for identifying individuals at risk and for
clinicians to prescribe preventive measures for these individuals. Current immunoassay technologies
typically measure the proteins at concentration above 10-12 M. The development of a detection method
that is rapid, cheap, and more sensitive than those currently available could revolutionize many medical
treatments in areas such as cancer. In this project, we aim to fabricate nanobiosensors with nanostructured
3D-electrodes to detect single protein molecules in blood.
Via these projects, students will achieve hands on experience in the design, fabrication and application of
the microfluidic devices and electrochemical micro(nano)biosensors.
22
SCMB Biotechnology Research Projects 2016 | Individual Contributors
ASSOCIATE PROFESSOR SASSAN ASGARI
School of Biological Sciences
Phone: 07 3365 2043
Email: [email protected]
Insect host-pathogen molecular interactions
In my laboratory, we are investigating the evolutionary adaptations that are employed by parasites and
pathogens of insects to avoid host immune defence reactions. This will further our understanding of the
interactions but also lead us to the discovery of biogenic molecules with agrochemical and pharmaceutical
properties with potential applications in biotechnology.
Examples of available projects are:
Project 1: Role of microRNAs in host-pathogen interactions
MicroRNAs are small non-coding RNAs that play important roles in gene regulation in metazoans, plants
and viruses. Their roles in development, cancer, apoptosis, immunity, longevity, and viral infections have
been established. We are investigating the role of these small molecules expressed from insect viruses or
insect host cells in host-pathogen interactions and virus biology. We are using a variety of host-pathogen
systems, including Dengue virus-, West Nile virus-, Wolbachia-mosquito interactions. This project is in the
most rapidly developing area of microRNA research and provides a basis for designing smart strategies to
control insects of medical or agricultural significance.
23
SCMB Biotechnology Research Projects 2016 | Individual Contributors
ASSOCIATE PROFESSOR
ANDREW C. BARNES
School of Biological Sciences & Centre for Marine Science
Phone: 07 3346 9416
Email: [email protected]
Host-microbial interactions in aquatic animals
Marine and aquatic animals exist directly immersed in an environment that supports abundant and diverse
microbiota. This provides both unique opportunities and challenges for aquatic animals that are not
experienced by their terrestrial counterparts. My research explores the interactions of marine fish and
invertebrates with predominantly bacterial associates, both beneficial and pathogenic, focusing on aquatic
animal health. Much of my research is applied, having strong collaborations with the aquaculture and
veterinary industry both in Australia and overseas.
Comparative immunology
At the molecular and cellular level, the first point of contact between aquatic animals and environmental
microbes is their immune system. We have explored the immune systems of invertebrates such as corals,
prawns and oysters, as well as commercially and ecologically important marine fish at both the molecular
and functional level. We have identified roles in pathogen exclusion and symbiont selection. At the applied
level we have exploited this to develop commercial vaccines for barramundi, improve vaccine adjuvants for
fish and to develop tools for marker-assisted selection of disease resistant oysters. At the fundamental level
we have identified the first functional immune proteins in reef-building corals and determined their roles in
microbial community control and selection of the symbiotic dinoflagellate.
Bacterial pathogenesis
Ultimately, most bacterial invaders are eliminated by macrophages. Therefore, understanding how
pathogens circumvent these phagocytic cells is critical in development of vaccine targets. We investigate
interactions of pathogenic bacteria with primary leucocyte cultures derived from commercially and
ecologically important marine fish species with a view to developing improved vaccines, or explaining why
particular epizootics have arisen. Current work focuses on evolution of the capsular operon of S. iniae in
response to on-farm vaccination, and on tracing origin and explaining pathogenesis of group B
Streptococcus in wild Queensland grouper using genomics and functional assays.
Microbial communities
Aquatic animals have complex microbial communities that strongly influence health and growth. The
complexity of the communities is confounded further by extremely high variability amongst individuals. We
investigate microbial communities with sufficient replication to provide data that can be used predictively
or to solve particular issues. In highly replicated studies we have shown strong host –specific selection of
bacterial associates in reef-building corals. We have also shown what happens to the metabolically active
gut microbiota of Atlantic salmon during the stress of warm summer water temperatures in Tasmania,
enabling formulation of novel more sustainable feeds to improve stability of the gut microbiome and
improve fish performance during the summer months.
Project 1: Serotype switching in marine streptococcus from barramundi and grouper
Project 2: Markers for immune cells in barramundi
24
SCMB Biotechnology Research Projects 2016 | Individual Contributors
PROFESSOR CHRISTINE BEVERIDGE
Centre for Integrative Legume Research
School of Biological Sciences
Phone: 07 3365 7525
Email: [email protected]
A new plant hormone
In a recent publication in the journal Nature we identified strigolactone as a new plant hormone. We now
understand that this hormone is involved in a range of processes in plants that are important for plant
productivity. We have several new mutants that affect shoot branching and which may act on this pathway.
Several neat projects are available elucidating the genetic and physiological function of the genes involved
and the pathways they control.
Novel plant signals
Plants respond to decapitation very rapidly via unknown processes. We have discovered several genes
which show changes in expression and may underpin this important developmental process. In this project
you will investigate these genes and other tools to determine how plants can respond so quickly to this
potentially devastating treatment.
Integration of plant development
We are interested in how the body plan of the shoot is controlled and how branching and flowering control
systems are integrated into developmental strategies adapted to the environment. We use genetic,
physiological and computational modelling (see our recent Plant Cell paper) to create and evaluate models
of the biological networks involved. In this research area, you will be allocated a tight project adapted to
your particular skills and needs.
25
SCMB Biotechnology Research Projects 2016 | Individual Contributors
ASSOCIATE PROFESSOR
JOANNE BLANCHFIELD
School of Chemistry & Molecular Biosciences
Phone: 07 3365 3622
Email: [email protected]
Synthesis of revolutionary synthetic vaccine constructs (project with Prof. Paul Burn)
We have a collaboration with Prof. Paul Burn that concerns the construction of fully synthetic vaccine
structures against HIV and Staphlycoccus aureus. For details of the project please contact Joanne
Blanchfield or Paul Burn. This project would involve:
• organic synthesis
• carbohydrate synthesis
• solid phase peptide synthesis
• cell culture and plasma stability assays and aseptic techniques
• assay development and molecule characterisation including use of HPLC, LC/MS, NMR, GC/MS
equipment.
Bioavailability of natural products from herbal extracts. (Project with Prof. James De Voss)
Herbal remedies are a major source of medical treatment for much of the world’s population.
Unfortunately, little is known about the fate of the natural products in the extracts or which, if any are
biologically active. We are offering a project that uses a cellular model of the small intestine (Caco-2 cell
monolayers) to investigate which natural products are likely to enter the blood stream after oral intake of
some popular herbal remedies. We also look closely at what changes the compounds undergo during
digestion and absorption.
• use of preparative and analytical HPLC equipment to isolate and identify potentially active compounds
from herbal extracts.
• performance of in vitro biological assays to determine permeability (Caco-2 cell assay), stability (CC2
homogenate assay, plasma stability) assays.
• Analytical analysis using LC/MS and HPLC of the solutions resulting from the in vitro assays.
26
SCMB Biotechnology Research Projects 2016 | Individual Contributors
PROFESSOR JIMMY BOTELLA
Plant Genetic Engineering Laboratory, School of Biological Sciences
Phone: 07 3365 1128
Email: [email protected]
Characterisation of heterotrimeric G-proteins in plants
Heterotrimeric G-proteins are extremely important in humans but very little is known about them in plants.
Our lab has established that G-proteins are involved in disease resistance in plants and are also important
contributors to yield. We recently discovered new members of the gene family in Arabidopsis and are now
investigating their cellular function. The projects involve molecular biology techniques, gene cloning,
produce genetic constructs and production and characterization of genetically modified plants.
Specific topics include:
• Characterization of the role of G-proteins in plant defence.
• G-protein control of yield.
• Role of G-proteins in cell death.
Plant defence against pathogenic fungi
Pathogenic fungi cause billions of dollars in loses each year and affect all of the important crops used for
human food production. We have recently discovered a number of genes involved in the defence against
this type of pathogens and are now devising strategies to produce resistant plants using genetic
transformation technologies. The projects involve cloning, molecular characterization of genes and study of
a number of transgenic lines with increased disease resistance.
27
SCMB Biotechnology Research Projects 2016 | Individual Contributors
PROFESSOR PAUL BURN
Director, Centre for Organic Photonics & Electronics (COPE)
School of Chemistry & Molecular Biosciences
Phone: 07 3346 7614
Email: [email protected]
The Centre for Organic Photonics and Electronics (COPE) is located on floor 9 of the Chemistry Building. The
Centre contains state-of-the-art synthesis laboratories, a Class 1000 clean room and a suite of instrument
rooms for the characterization of materials and opto-electronic devices. The mission of the Centre is
develop ‘organic materials’ that can be used in high performance cutting edge technologies including
sensors, solar cells, flat panel displays, plastic electronics, and fuel cells. Honours students working in these
areas will learn the key skills of synthetic chemistry and characterization of small and macromolecules, the
latter including dendrimers (branched macromolecules) and polymers. In addition, the Honours student will
have the opportunity to work with physics colleagues in interpreting the properties of the materials and
device performance, which can lead to the design of the next generation of materials. Of particular
relevance to Biotechnology students we are offering projects in the area of new sensing technologies.
However, we would also be willing to consider students who have an interest in the other areas of research
in COPE.
Project: Sensors
Sensors play a vital role in many different technologies including the detection of pollution, drugs, and
explosives. Recent global events have raised concerns over national security and counter-terrorism
measures in civilian areas. In particular, the deployment of hidden explosives over large populated areas
requires creative and feasible preventative measures. Currently the most sensitive detectors for explosives
are canines. We are therefore interested in developing sensors that are more sensitive and selective than
canines, and are using the sensing of explosives as a model system for detecting analytes. The aim is to
develop a general sensing technology that can be applied across a broad range of analytes. Most current
methods for detecting explosives are slow and the equipment cumbersome. To this end we are developing
an explosives sensor based on semiconducting organic materials that will be portable, selective and fast.
These materials rely on electron-deficient analytes (explosives) to quench their luminescence, giving a
reduction of the normal signal upon binding. For example, dendrimer 3 can detect 1,4-dinitrobenzene and
we will be synthesizing and testing new materials against a variety of analytes.
28
SCMB Biotechnology Research Projects 2016 | Individual Contributors
PROFESSOR ROB CAPON
Institute for Molecular Bioscience
Phone: 07 3346 2979
Email: [email protected]
Biodiscovery: From Biodiversity and Bioactives to Biology and Beyond
The research interests of my group centre on the detection, isolation, characterisation, identification and
evaluation of novel bioactive metabolites from Australian marine and terrestrial biodiversity. These
metabolites span all known biosynthetic structure classes including many molecules new to science, and
their study requires the use of sophisticated chromatographic, spectroscopic and chemical technologies.
Natural products uncovered during our investigations represent valuable new leads in the search for drugs
with application in the fields of human and animal health and crop protection, have potential as molecular
probes to better interrogate and understand living systems, and could find application as biological control
agents.
The research group manages an extensive network of collaborators across many scientific disciplines, in
industry, academia and government, both in Australia and overseas, which allow it to target such
therapeutic indications as infectious and neurodegenerative diseases, cancer, pain, diabetes and obesity, as
well as invasive animal and pest control through chemical ecology, and gene activated microbial
biodiscovery.
Individual research projects can (on enquiry) be negotiated and structured around the following:
Natural Products Chemistry: the isolation, and spectroscopic and chemical analysis of, secondary
metabolites from marine and terrestrial plants, animals and microbes, with a view to better exploring and
understanding “natural” chemical space.
Synthetic Organic Chemistry: synthesizing new bioactive natural products, to test and refine novel
pharmacophores, to build knowledge of and prioritize new drug lead candidates, with a view to better
exploring and understanding “synthetic” chemical space.
Microbial Metabolism: learning to better regulate and express silent secondary metabolite gene clusters,
to better explore and make use of the full spectrum of “natural” chemical space defined by the microbial
genome.
Chemical Ecology: to acquire and use knowledge of how invasive pests (ie cane toad) make use of
chemistry in the form of defensive secretions and pheromones, and to use this knowledge to develop safe,
effective and species selective control solutions.
29
SCMB Biotechnology Research Projects 2016 | Individual Contributors
PROFESSOR BERNIE CARROLL
School of Chemistry and Molecular Biosciences
Phone: 07 3365 2131
Email: [email protected]
RNA interference (RNAi) and gene silencing in Arabidopsis
Gene silencing is a highly conserved process in plants and animals, and is of fundamental importance to
developmental regulation of gene expression, defence against viruses, transposon silencing, adaptation to
environments and genome evolution. Gene silencing is also of immense relevance to biotechnology. We
are using Arabidopsis as a eukaryotic model for studying the mechanisms of gene silencing.
Intercellular spreading of gene silencing.
Remarkably, when gene silencing is triggered in cells of plants and animals, it can spread throughout the
organism. The intercellular movement of RNA signals plays a fundamental role in plant development and
defence against viruses. We are using a forward genetic approach and map-based gene cloning to elucidate
the mechanisms of systemic movement of gene silencing in Arabidopsis.
Intron splicing regulates gene expression in Arabidopsis.
The role of introns has puzzled molecular biologists since their discovery in 1978. We recently showed that
intron splicing protects genes from being silenced in Arabidopsis3. Defective intron splicing has been
associated with genetic diseases in both plants and humans. This project aims to identify novel genes and
proteins involved in these processes.
Genetic engineering of pest resistance in plants based on RNA.
RNAi has immense potential for engineering crop resistance to insect pests, and decreasing the use of toxic
insecticides that threaten ecosystems and human health. We are expressing RNAi molecules in plants to
silence essential insect genes and confer insect resistance.
MicroRNAs involved in high temperature-tolerance
in plants.
We are using modern molecular techniques and
computing to identify miRNAs for high-temperature
tolerance in plants. We are using transgenic
approaches to modify the expression of these
miRNAs to improve high temperature-tolerance in
plants.
Selected recent publications:
1. Brosnan et al. (2007) Nuclear gene silencing directs reception of long-distance mRNA silencing in
Arabidopsis.
PNAS 104, 14741-14746.
2. Gursanscky et al. (2011) Mobile microRNAs hit the target. Traffic 12, 1475-82.
3. Christie et al. (2011) Intron splicing suppresses RNA silencing in Arabidopsis. Plant Journal 68, 159-167.
30
SCMB Biotechnology Research Projects 2016 | Individual Contributors
DR MARINA CHAVCHICH
Australian Army Malaria Institute
Phone: 07 3332 4826
Email: [email protected]
Malaria Biology, Malaria Drug Discovery and Resistance
In my research laboratory we are studying the malaria parasite, Plasmodium falciparum. Malaria infects
approximately 200-300 million people annually which results in 2-3 million deaths. Understanding the
biology of the parasite will lead to novel therapeutic options to treat and prevent the disease. In particular,
we are focussing our studies on the malarial cell cycle machinery and the respective signal transduction
pathways to identify and validate novel malaria drug targets. Additionally, we are interested in
understanding the molecular mechanisms of antimalarial drugs and the development of drug resistance.
Identification of novel anti-malarial compounds
P. falciparum will be cultivated and assayed in an ex vivo/in vitro growth inhibition assay to test compounds
for anti-malarial activity. Compounds will be tested against both drug sensitive and resistant parasites to
determine a drug resistance index. Selected compounds demonstrating significant activity will be further
tested in drug combination studies to find suitable partners that yield a synergistic effect with increased
potency. Structure Activity Relationships (SAR) will be evaluated and used to select additional compounds
for testing. Compounds will be selected from commercially available libraries and obtained from
collaborations with medicinal and natural product chemists. This project will involve dose-response
inhibition assays, malaria cultivation, and SAR analysis.
Cell cycle control and developmental regulation of the malaria parasite
The malaria parasite undergoes multiple rounds of DNA replication in the absence of mitosis in a process
known as schizogony. In most eukaryotic cells, DNA replication is followed immediately by mitosis. Cyclin
Dependent protein Kinases (CDKs) regulate the progression of the cell cycle and ensure that DNA
replication and mitosis occurs in a highly regulated fashion. CDKs are present in the malaria parasite
however their role in cell cycle control must be unique in order to regulate schizogony. To further
understand the role of malaria CDKs, studies are underway to determine substrate specificity and the
regulatory mechanisms of autophosphorylation and the binding of effector proteins. This project will
involve protein expression and purification, kinase assays, enzyme kinetics, DNA replication assays,
Western blots, immunofluorescence microscopy, two-hybrid protein-protein interaction assays.
Pursue the cyclin dependent protein kinases (CDK) as novel malaria drug targets
CDKs are drug targets for numerous diseases to include cancer, neurological disorders, cardiovascular
disease and recently, parasitic infections. Several malarial CDKs have been developed into 96 well
microtiter plate inhibition assays. Compounds will be screened against the malarial CDKs with particular
emphasis on Pfmrk. Compounds demonstrating significant inhibitory activity, will be tested against the
homologous kinases to deselect compounds that cross react with the human homologs. Compounds will
also be tested against the malaria parasite to establish a correlation between inhibition of the CDK and
parasite death. Iterative screening, along with a detailed SAR analysis, should identify potent and selective
malarial CDK inhibitors. Genetically modified parasites that overexpress Pfmrk, will be used to validate
Pfmrk as a drug target. This project will involve protein expression and purification, enzyme kinetics, kinase
assays and dose-response inhibition assays.
31
SCMB Biotechnology Research Projects 2016 | Individual Contributors
PROFESSOR DAVID CRAIK
Institute for Molecular Bioscience
Phone: 07 3346 2019
Email: [email protected]
The Craik lab discovers novel peptides for applications in drug design. Their work has the potential to lead
to new drugs for the treatment of a wide range of diseases, including cancer, cardiovascular disease,
infectious disease and pain.
Project 1: Novel circular proteins: templates in drug design
Until a few years ago circular proteins were virtually unknown, but
over recent years we have discovered and structurally characterised
a family of circular proteins in plants called the cyclotides. These
molecules were originally discovered because of their uses in native
medicine as uterotonic agents to aid childbirth and in screening
programs of plant extracts against HIV. We have found that the
molecules contain an unusual structural motif called a cystine knot in
which two disulfide bonds and their connecting backbone form a ring
in the structure that is threaded by a third disulfide bond. Combined
with a circular backbone this knot makes the cyclotides exceptionally
stable, making them potentially valuable frameworks in peptidebased drug design. Cyclotides are resistant to enzymatic degradation
and are stable in biological fluids, unlike most peptide-based drugs.
This project involves the discovery and structural characterisation of new cyclotides in plants. We wish to
determine the natural structural diversity of the framework so that we can best design novel analogues in
which new biological activities are grafted onto the framework. The project will teach skills in natural
products isolation and structure determination by NMR spectroscopy.
Project 2: Structure-activity relationships in conotoxins: leads in drug design
Conotxins are small disulfide rich toxins from the venoms of cone snails. They inhibit a range of ionchannels and are regard as valuable leads in drug design, with four conotoxins currently in clinical trials for
various neurological conditions and as analgesic molecules. As part of an ARC funded project we are
identifying new conotoxins, as well as synthetically varying known conotoxins with the broad goal of
producing novel leads in drug design or neuropharmacological probes. The aim of this project is to
determine the structures of these novel conotoxins. The project will teach skills in peptide purification and
structure determination by NMR spectroscopy.
Project 3: Harnessing plants to produce peptide drugs: drugs in plants
We have recently discovered the common machinery that diverse plants use to manufacture stable cyclic
peptide frameworks as well as the conserved sequences that allow processing from their precursors. We
have performed proof-of-concept work that demonstrates we can genetically modify a reference plant so
that it synthesises a protease inhibitor that is a potent lead as a treatment for prostate cancer. Our
hypothesis is that we can further enhance this system to produce low-cost synthesis of tailor-made drugs in
seeds through genetic engineering. The technology developed from this project will allow stable peptide
drugs to be manufactured at low cost and, as a more “organic” drug source, has the potential to improve
patient compliance as well as be adaptable to production systems in third-world nations. This project will
teach skills in plant genetic transformation, peptide analysis, and genetic analysis.
32
SCMB Biotechnology Research Projects 2016 | Individual Contributors
PROFESSOR JAMES DE VOSS
School of Chemistry & Molecular Biosciences
Phone: 07 3365 3825
Email: [email protected]
My group is concerned with biological and synthetic chemistry and in particular with the application of
chemical principles to the understanding of biological processes. Most projects are a blend of disciplines in
bio-organic chemistry: synthesis, structure determination, molecular biology, protein purification. A range
of techniques is employed, ranging from the biochemical (e.g. PCR, gel electrophoresis) to the chemical
(e.g. NMR, HPLC, GC/MS). The following areas illustrate the research in my laboratory but the exact project
will be determined by the student’s interests.
Project 1: Cytochromes P450: P450s catalyse an amazing variety of oxidative transformations, ranging from
simple alkene epoxidation all the way through to oxidative C-C bond cleavage. They are of interest as they
(i) are often unique enzymes in a biosynthetic pathway and as such represent new targets for
chemotherapeutic agents or (ii) are extremely efficient catalysts that offer the potential of developing
tailored oxidative catalysts for synthetic transformations. We are interested in understanding the
mechanism of action of a number of P450s. One example is CYP61, a unique P450 involved in steroid
biosynthesis in fungi and other pathogenic organisms. As such it represents a potential target for novel
chemotherapeutics. CYP61 catalyses an unusual reaction for a P450, namely the dehydrogenation of an
alkane to an alkene. However, essentially nothing is known about the exact structure of the substrate, the
stereochemistry of the reaction or its mechanism. Projects in this area will involve the synthesis of
mechanistic probes, the analysis of the products of enzyme-catalysed reactions, characterisation of enzyme
mutants and design and synthesis of inhibitors.
Project 2: Constituents of
Medicinally Used Herbs:
Whilst herbal medicines are
widely used and have a long
history of such use, their
chemical constituents are
often poorly characterised. In
collaboration with a local
company we have embarked
upon a program of phytochemical characterisation of a number of therapeutically prescribed herbs. The
results have been surprising with a number of previously unknown compounds isolated from supposedly
well-characterised species. This project would involve the isolation, chromatographic purification and
structure determination (especially employing 1D and 2D nmr) of the chemical constituents of selected
herbs. The structures of some recently isolated compounds are given below.
Relevant Recent Publications
1. Slessor, Kate E., Farlow, Anthony J., Cavaignac, Sonia M., Stok, Jeanette E., De Voss, James J. Oxygen
activation by P450(cin): Protein and substrate mutagenesis Arch. Biochem. Biophys. 2011, 507 154-162.
2. N. J. Matovic, J. M. U. Stuthe, V. L. Challinor, P. V. Bernhardt, R. P. Lehmann, W. Kitching and J. J. De Voss
The Truth about False Unicorn (Chamaelirium luteum): Total Synthesis of 23R,24S-Chiograsterol B Defines
the Structure of the Major Saponins from this Medicinal Herb Chem. Eur. J. 2011 17, 7578-91.
33
SCMB Biotechnology Research Projects 2016 | Individual Contributors
DR ANNETTE DEXTER
Australian Institute for Bioengineering & Nanotechnology (AIBN)
Phone: 07 3346 3199
Email: [email protected]
Research area: Designer peptides for biomedical and industrial applications
Designer peptides are attractive building blocks for preparation of novel functional nanomaterials. Peptides offer
stimuli-responsiveness, biocompatibility, predictable folding and capacity for sustainable production. By
employing and modifying a key structural motif of native proteins, the amphipathic alpha-helix, we have
developed short designer peptides that show promise as responsive hydrogels for wound healing, tissue
engineering and drug delivery or, in a separate class, as environmentally-friendly switchable surfactants.
Dr Dexter is a co-founder of UQ start-up company Pepfactants Pty Ltd, and is involved in commercialization of
peptides as “green” surfactants as well as biocompatible gelling agents.
Project 1: Peptide hydrogels for burn healing
Burns represent a major category of accidentally acquired injury, with over 130,000 injuries in this class in
Australia each year. Currently, all children who sustain deep dermal burns will heal with unsightly scars. Scarred
areas fail to grow with the child and often cause contractures that require repeated surgery. The scarred tissue is
weaker than normal tissue and is prone to drying and ulceration. Pressure garments and silicone sheets are the
only proven methods to reduce scar formation, however they must be worn for at least a year and the results
are often disappointing. Prevention of scarring following deep burns is thus an important medical goal with longterm consequences for quality of life of burn victims. We are developing peptide hydrogels as advanced wound
dressings with the potential to accelerate re-epithelialisation of burn wounds to prevent scarring. An Honours
project is available in formulating and testing hydrogels for the treatment of burn wounds.
Project 2: Peptides as surfactants for eco-friendly industrial fluids
Industrial fluids are lubricating and cooling fluids extensively used in industrial machining operations. As
currently formulated they represent both an occupational health and safety hazard for machine operators, and a
waste disposal problem at the end of their lifecycle. Oil-in-water industrial fluid emulsions are usually
formulated with petrochemical surfactants that can break down to give hazardous sulfhydryl gases, cause
painful skin lesions on prolonged contact, and form emulsions that are difficult to separate for the disposal of oil
and water phases. We are currently investigating the use of peptides as alternate surfactants for industrial fluids,
in conjunction with a major industry partner. The peptides offer both lower toxicity as sulfur-free and
biocompatible surfactants, and a capacity for emulsion switching to allow clean separation of oil and water at
the end of the emulsion lifecycle. An Honours project is available in formulating and testing cutting fluids for
lubrication in metal-working and recyclability of the functional components.
Project 3: Bioproduction of peptides as hetero- or homoconcatemers
The adoption of peptides for materials applications, either in the biomedical or industrial space, will depend on
methods for low-cost, large-scale production. Currently, most peptides tested for drug or other applications are
produced by solid-phase synthesis (a costly method with high environmental impact) and are subsequently
purified by expensive chromatographic methods. While short peptides can be produced in bacterial hosts by
fusion to a carrier protein, this approach has poor efficiency, as most of the product obtained (>80%) is carrier
protein rather than the target peptide. We recently developed a novel method for expressing ionic surfactant
peptides, by using heteroconcatemers of oppositely-charged peptides to form a coiled-coil miniprotein. The
resulting protein is stable to heat and proteases and can be purified by simple precipitation steps. We are now
seeking to extend this approach to gel-forming peptides, to facilitate the use of such peptides in biomedical
applications. An Honours project is available in the design, expression and downstream processing of a gelling
peptide for biomedical use.
34
SCMB Biotechnology Research Projects 2016 | Individual Contributors
ASSOCIATE PROFESSOR PAUL EBERT
School of Biological Sciences
Phone: 07 3365 2973
Email: [email protected]
Project 1: Functional genomics of ageing
Despite a significant increase in human life expectancy, old age is still
characterised by physiological changes that manifest themselves as age-related
diseases. The ultimate goal of this research is to increase the disease-free lifespan
of individuals. We approach this problem in two ways: The first is to investigate
the ageing process itself, whereas the second is to model disease of old age and
to test the effect of drug therapies. We are using the genetic model organism,
Caenorhabditis elegans, as it is the leading model organism for lifespan research.
We have identified a novel longevity gene and are now determining its mode of
action and potential interaction with diseases of old age. The project involves
microarray analysis, targeted epigenetic gene suppression, genome sequencing,
bioinformatics and genetics.
Project 2: Cloning of phosphine resistance genes from pest insects:
Stored grain is protected from insect pests by fumigation with
phosphine, but some insects are now resistant to 600 times the
normal lethal dose of phosphine. Several new fumigants have been
proposed, but their modes of action and interaction with other
fumigants and with phosphine resistant insects is unknown. This
project will be carried out in collaboration with the Queensland
Department of Agriculture, Fisheries & Forestry and will characterize
these new fumigants to help lead the grains industry into a new
future. This project will involve toxicology testing, genome sequencing, bioinformatics and perhaps some
work with C. elegans.
35
SCMB Biotechnology Research Projects 2016 | Individual Contributors
ASSOCIATE PROFESSOR DARRYL EYLES
Queensland Brain Institute
Phone: 07 3346 6370
Email: [email protected]
Studies in our lab relate the major epidemiological findings in schizophrenia with how the brain may be
altered during development. Projects relate directly to the epidemiology implicating certain risk factors
during gestation that correlate with increased schizophrenia in offspring.
One prominent risk factor we have established is developmental vitamin D deficiency.
Project: The effect of maternal vitamin D deficiency on dopamine neuron ontogeny
The student would examine the brains of embryonic animals from vitamin D deficient Dams. The student
would study the timing of the expression of crucial dopaminergic transcription regulators in the developing
mesencephalon. The student would also conduct in vitro experiments examining the activation status of
the receptor for vitamin D in these same cells. These studies will help to inform the larger structural and
behavioural picture emerging in this model strongly implicating dopaminergic dysfunction.
Data from both these studies could have considerable public health implications regarding preventative
measures in utero for developmental diseases such as MS and schizophrenia!
Students interested in honours projects or higher degrees should contact me. I can be found in the
Queensland Brain Institute, The University of Queensland, Brisbane, Qld 4072, Australia.
36
SCMB Biotechnology Research Projects 2016 | Individual Contributors
PROFESSOR DAVID FAIRLIE
Institute for Molecular Bioscience
Phone: 07 3346 2989
Email: [email protected]
Our research programs ( http://fairlie.imb.uq.edu.au/ ) link chemistry to biologically important problems
related to pathogenesis and treatment of disease. Students develop expertise in organic, medicinal or
biological chemistry; learning principles of molecular design, synthesis (solid and solution phase,
combinatorial chemistry, microwave-assisted), structure determination (2D NMR spectroscopy), or
biological properties through interactions with proteins. Outcomes are new structures, reactions,
mechanisms, enzyme inhibitors, protein agonists/antagonists, and new drugs.
Each Hons student (http://fairlie.imb.uq.edu.au/researchers.php?id=24; id=22) produces significant
publishable results from their project (e.g. Synthesis of antagonists for inflammatory GPCRs; Design and
Synthesis of anti-inflammatory phospholipase inhibitors; Evaluation of nociceptin analogues as potent
agonists and antagonists of Opioid Receptors; Metal clips for fixing peptides in alpha helices).
Hons projects are tailored around the interests of students. Some representative projects are:
Project 1: Antagonists of human G protein coupled receptors
Many human diseases start by proteins acting on surfaces of cells. We wish to synthesize small organic
compounds that bind tightly to cell surfaces and prevent or mimic such actions, thereby regulating
intracellular signaling pathways associated with cancer, inflammatory conditions, cardiovascular and
Alzheimer’s diseases. This project involves 90% organic synthesis (using solution and solid phase
techniques, NMR spectroscopy, combinatorial and microwave synthesis methods) and collaboration with
other members of the group who will undertake most of the biology, unless the student also wishes to
learn biology. (For background see: Chem Rev 2007, 107, 2960-3041).
Project 2: Inhibitors of Proteases
Proteolytic enzymes are involved in the synthesis, turnover and degradation of all proteins and are
validated therapeutic targets in human diseases. This project will design potent and selective inhibitors of
proteases associated with inflammatory diseases. Either a cysteine protease or a serine protease will be the
enzyme target. The project involves synthetic chemistry, collaboration with a computer modeller, and
willingness to screen compounds every 2-3 weeks in a 2 hour bioassay. Resulting compounds will be antiinflammatory agents. Background (J. Med. Chem. 2000, 43, 305).
Project 3: Protein Surface Mimics
We have a range of projects available that are directed towards downsizing a bioactive region of a protein
to a small organic molecule that can structurally and functionally mimic key protein surfaces. Background
reading: Shepherd NE et al; Modular Alpha Helical Mimetics With Antiviral Activity Against Respiratory
Syncitial Virus. J. Am. Chem. Soc. 2006, 128, 13284-13289. Shepherd NE et al; Left- and Right-Handed
Alpha-Helical Turns in Homo- and Hetero-Chiral Helical Scaffolds. J Am Chem Soc. 2009, 131, 15877-15886.
Ma MT et al; Metal Clips That Induce Unstructured Pentapeptides To Be Alpha Helical In Water. J Am Chem
Soc 2009, 131, 4505-4512.
For more information: contact David or visit http://fairlie.imb.uq.edu.au/
37
SCMB Biotechnology Research Projects 2016 | Individual Contributors
ASSOCIATE PROFESSOR CAMILE FARAH
Group Leader, Oral Oncology Research Program
University of Queensland Centre for Clinical Research (UQCCR)
Phone: 07 3346 6030
Email: [email protected]
PROGRAM MEMBERS:Academic & Research Staff
• Associate Professor Camile Farah (Group Leader)
• Dr Andrew Dalley (Postdoctoral Research Officer)
• Dr Pauline Ford (Senior Lecturer)
• Mr Anthony Chan (Histology Technician). Adjunct
Academic Staff
• Dr Martin Batstone (Maxillofacial Surgeon, RBWH)
• Dr Maurie Stevens (ENT Surgeon, RBWH)
• Dr Borjana Simanovic (Visiting Dentist)
• Dr Colin Ades (QML Pathology)
Research Higher Degree Students
• Dr Ahmad Abdul Majeed (PhD),
• Dr Maryam Jessri (PhD)
• Ms Fatima Dost (MPhil).
Concurrent BDSc/MPhil Students
• Ms Kristine Allen
• Ms Yasitra Lallaq
• Ms Keziah John
• Dr Ian Housego
• Dr Glenn Francis (PhD)
• Anthony Crombie (MPhil)
• Dr Phan Nguyen (PhD)
• Ms Kelsey Moore (MPhil)
• Mr Nirav Bhatia
• Ms An Vu
• Ms Brie Kwon
• Dr John Webster
• Mr Sean Currie
• Ms Jennifer Wu
• Mr Bing Lee
Honours Students
• Mr Aidan Major, Mr Luke Pitty
PROGRAM SUMMARY:
The Oral Oncology Research Program leverages work regarding various bio-markers of oral cancer and oral
epithelial dysplasia which are either unique to the oral mucosal situation or shared across malignancies in other
sites. The program leverages a range of novel technologies, including optical fluorescence imaging and narrow
band imaging, to be able to diagnose oral cancer at its earliest stages, thus allowing early forms of treatment to
be applied with maximal effect. The program also investigates the role that cancer stem cells play in the
propagation and recurrence of cancerous and pre-cancerous lesions. The underlying premise of this program
looks at creating a molecular signature for pre-cancerous conditions that can be used as a diagnostic test to
either replace or supplement standard histopathological interpretation of oral epithelial dysplasia and oral
squamous cell carcinoma. To complement the program’s work on the biological mechanisms of oral cancer, we
are undertaking projects to examine oral pre-cancerous conditions at the population level. Clinical and
epidemiological studies of defined at-risk populations are underway which will determine the burden of oral
mucosal disease as well as the relative importance of a range of risk factors for these groups. This information is
fundamental to planning for oral health services and public health interventions which are appropriate and cost
effective. The work of the group is undertaken at the UQ Centre for Clinical Research based at the Royal
Brisbane & Women’s Hospital at Herston. This program is funded by grants from the National Health & Medical
Research Council, Cancer Australia, Cancer Council Queensland, Queensland Government Smart Futures Fund,
RBWH Foundation, and the Australian Dental Research Foundation. The group has collaborations with Agilent
Technologies, Life Technologies, Olympus Australia, Colgate-Palmolive Australia, and the Institute for Urban
Indigenous Health.
AVAILABLE PROJECTS: Project 1: Molecular profiling of cancer stem cell / Project 2: miRNA expression in oral
epithelial dysplasia
38
SCMB Biotechnology Research Projects 2016 | Individual Contributors
ASSOCIATE PROFESSOR VITO FERRO
Deputy Director, Biotechnology Program
School of Chemistry & Molecular Biosciences
Phone: 07 3346 9598
Email: [email protected]
My research interests encompass carbohydrate chemistry and medicinal chemistry, with a focus on the
synthesis of compounds to probe and/or inhibit carbohydrate-protein interactions involved in disease
processes. Of particular interest is heparan sulfate (HS) and the development of HS-mimetics as potential
drugs for cancer and various other diseases. Previous work in this area resulted in the discovery of PG545, a
potent inhibitor of angiogenesis and metastasis that recently entered Phase I clinical trials in cancer
patients.
1. Development of a fluorometric assay for heparanase
Heparanase is a glycosidase that cleaves HS in the extracellular matrix and facilitates metastasis of tumour
cells and vascular remodelling associated with angiogenesis. PG545 is an example of a heparanase inhibitor
with potent in vivo activity in metastatic and angiogenic models. Despite the advancement to clinical trials
of inhibitors, heparanase research has been limited by the lack of a simple and robust assay for enzymatic
activity. This project aims to address the situation by the synthesis of novel fluorogenic substrates for
heparanase.
2. Synthesis of pharmacological chaperones for lysosomal storage diseases
Lysosomal storage diseases (LSD) are caused by mutations in enzymes that degrade polysaccharides such as
HS, resulting in the accumulation of undegraded substrate in the lysosomes of cells. Some patients may be
treated with enzyme replacement therapy. Unfortunately, the replacement enzyme cannot cross the
blood-brain barrier and thus cannot treat the neurological symptoms associated with severe cases. The
aims of this project are to develop small molecules for the treatment of LSD, which unlike enzymes, are
capable of crossing the blood-brain barrier and thus may offer relief of neurological symptoms. The
compounds are designed to act as “chaperones” to protect the defective enzyme from degradation and
restore enzyme activity to sufficient levels to alleviate symptoms.
3. Glycosylated liposomes for targeted delivery of siRNA
Targeted delivery to a specific cell type is desirable to improve the effectiveness and specificity of siRNA for
gene silencing. The aim of this project is to generate specifically glycosylated liposomes that will enable
delivery of siRNA to particular cell types possessing receptors for these glycans.
4. Synthesis of inhibitors of virus-cell attachment
Many viruses, including HSV and HIV, use HS as an entry receptor or co-receptor. This project will focus on
the synthesis of novel HS mimetics that inhibit virus-cell attachment and possess virucidal activity.
39
SCMB Biotechnology Research Projects 2016 | Individual Contributors
DR DONALD GARDINER
CSIRO Plant Industry / Queensland BioScience Precinct, UQ-St. Lucia Campus
Phone: 07 3214 2370
Email: [email protected]
FUSARIUM PATHOGENESIS IN WHEAT
The lab is currently researching mechanisms of pathogenicity and virulence in fungal pathogens. We work
with pathogens that cause crown rot and head blight disease of wheat and also pathogens that cause
Fusarium wilt disease in a number of plant species.
Students in the lab will be given their own project under the supervision of a more experienced lab
member (Jason Carere, a postdoctoral fellow [email protected]) with the hope of producing
publishable results. A position is currently available on the current project:
Characterization of a hydrolase involved in defence compound degradation
This hydrolase from Fusarium pseudograminearum has been shown to be important for pathogenesis in
wheat. The project involves the expression and purification of this protein to determine possible substrates
which it acts on in planta. This will be accomplished through the use of enzymatic assays and x-ray
crystallography. This work will improve our understanding of the chemicals plants produce to protect
themselves and the mechanism by which pathogens evade those defences.
If you have any questions or would like further information please contact Don or Jason by email.
40
SCMB Biotechnology Research Projects 2016 | Individual Contributors
PROFESSOR IAN GENTLE
School of Chemistry & Molecular Biosciences
ARC Centre of Excellence for Functional Nanomaterials
Phone: 07 3365 4800
Email: [email protected]
Research in the Surface Chemistry Group is concerned with the self-assembly of materials at interfaces, a
field of research which encompasses thin film methods and other surface processes. Thin film techniques
have important technological applications in the construction of devices with useful electronic, optical or
optoelectronic properties, and interfaces are also important to many biological systems. Methods of
characterisation used include grazing incidence X-ray and neutron scattering and spectroscopy (facilities at
the OPAL Neutron Source in Sydney, the Australian Synchrotron in Melbourne or overseas facilities are
normally used for this purpose), X-ray reflectometry, X-ray photoelectron spectroscopy (XPS) and atomic
force microscopy (AFM), depending on the project. At UQ, the facilities for characterisation of thin films
and materials (in the Centre for Microscopy and Microanalysis) are state of the art. These include a $1.1M
imaging XPS, a Digital Instruments NanoScope scanning probe microscope, an Anton Paar Small Angle X-Ray
Scattering instrument and two Bruker X-ray diffractometers.
New Directions towards High Energy Supercapacitors: Graphene-based Multifunctional Electrodes
Supercapacitors with high power density and long life span are the most promising solutions beyond
lithium ion batteries to power electric vehicles, transportation and electronic devices. However, the low
energy density of supercapacitors is a major impediment to their development. This project aims to address
the materials and device challenges in high energy supercapacitors, and to propose guidelines for electrode
design principles, materials synthesis methodology and device configuration strategy. The core concept of
this research is to optimize the performance of graphene-based electrodes by tailoring nanoporous
structure, lattice dopants, surface functionalities and mechanical properties, and most crucially, to
understand the basic electrochemical processes.
Specific objectives are to:
•Synthesise
heterogeneous
graphene-based
nanosheets with desirable nanoporosity, lattice dopants
and surface functionality;
•Assemble multifunctional graphene-based electrodes
combining electrochemical reactivity and mechanical
flexibility;
•Understand the mechanisms of electrochemical
interfacial reactions and inner-pore ion transport to
optimize overall performance of the graphene-based
multifunctional electrodes.
This project will be carried out in collaboration with Dr
Da-Wei Wang. It will involve extensive use of chemical and surface synthetic techniques, structural
characterisation by advanced methods described above, combined with electrochemical measurements.
Depending on the rate of progress, there may be the opportunity for prototype supercapacitor device
construction using the new materials developed in the project.
41
SCMB Biotechnology Research Projects 2016 | Individual Contributors
PROFESSOR ROBERT G GILBERT
Centre for Nutrition & Food Sciences
School of Chemistry & Molecular Biosciences
Phone: 07 3365 4809
Email: [email protected]
Biosynthesis-structure-property relations for starch and glycogen
Starch provides more than half the world population’s calorific intake; glycogen is our body’s glucose
buffer. These are at first sight simple homopolymers of glucose, but their structure spans many levels of
complexity, with features ranging from nm to mm. These structural features strongly influence nutritional
value for humans, and how well glycogen is effective in controlling blood sugar (and hence propensity to
diabetes). In synthetic polymer science and technology, the paradigm for understanding material
properties, and producing materials with improved properties, is well established as synthesis controls
structure controls properties. The equivalent has been impossible for starch and glycogen: one changes the
genetics (biosynthesis) to try to obtain cereals with desirable properties—better digestibility for managing
and reducing obesity, diabetes and colo-rectal cancers—and drug targets for diabetes through glycogen
synthesis enzymes. This project will greatly expand current knowledge, through our unique experimental
and theoretical tools, to examine the structure of these polymers and then to relate the structural features
to both biosynthesis and to properties.
Examples of available projects :
Project 1: Kinetics of enzymatic degradation of starch and glycogen
This project will examine the rates at which starch is degraded by enzymes in human digestion, and how
glycogen in different organs is degraded to provide blood sugar when needed physiologically. This project
will examine the kinetics of these processes in vitro, to shed light on the corresponding in vivo processes
which are of major importance in controlling obesity and diabetes.
Project 2: Genetics/structure relations: experiment
There is no detailed knowledge on which genes control the extent of starch/glycogen branching at the
micro- or nano-structural level. There is also little information on the effects of environmental conditions
on the differential expression of the genes, nor the extent of genetic variation in these gene families. This
project will examine polymer structures in varieties obtained and characterized by modern techniques in
molecular biology and biotechnology to link the genome (gene) to phenome (structure) with reference to
growth conditions. Interpreting these data will yield information on the detailed mechanisms by which
enzymes of specific structure control particular aspects of starch structure.
Molecular structural differences between type-2-diabetic and healthy glycogen. MA Sullivan, J Li, C Li, F
Vilaplana, D Stapleton, AA Gray-Weale, S Bowen, L Zheng, RG Gilbert. Bio¬macro¬¬¬molecules 12 1983
(2011); Molecular weight distributions of starch branches reveal genetic constraints on biosynthesis. AC
Wu, RG Gilbert. Biomacromolecules, 11 3539 (2010); Amylose content in starches: towards optimal
definition and validating experimental methods. F Vilaplana, J Hasjim, RG Gilbert. Carbohydrate Polymers
88 103 (2012)
42
SCMB Biotechnology Research Projects 2016 | Individual Contributors
PROFESSOR ELIZABETH GILLAM
School of Chemistry & Molecular Biosciences
Phone: 07 3365 1410
Email: [email protected]
Catalytic promiscuity and artificial evolution of P450
enzymes
The cytochromes P450 are one of the most functionally
versatile groups of enzymes known. They carry out
diverse roles in Nature because they can catalyse an
extraordinary range of chemical transformations,
ranging from aromatic/aliphatic hydroxylation and
heteroatom oxidation, to group transfers, ring
expansion/contraction, coupling reactions, and C-C
bond cleavage. This makes them ideal starting materials
for engineering designer biocatalysts for difficult
chemical reactions.
Our group is interested in finding out how P450s work
and how they can be made to work better.
Project 1: Artificial evolution: better, faster, more specialised P450s can accelerate drug development
and clean up environmental pollutants
We are using artificial (or directed) evolution to generate libraries of mutants from naturally-occurring P450
forms with the aim of engineering catalysts with properties enhanced by orders of magnitude over those
found in naturally occurring enzymes.
Project 2: What determines the catalytic promiscuity of P450s?
Collectively a handful of P450s metabolise ~ 95% of all drugs to which humans are exposed as well as
innumerable environmental chemicals. This is a truly exceptional variety of substrates. Our aim is to
determine how these enzymes can show such extreme catalytic promiscuity using a range of biophysical
and molecular techniques.
Project 3: P450 Nanodiscs for biosensors (with Prof. Paul Bernhardt)
Since P450s respond to such a variety of different substrates they are well suited for use as biosensors to
detect trace environmental contaminants, drugs and other chemicals. We will formulate P450s into
nanodiscs – very small protein-bounded lipid bilayer discs – to characterise their electrical properties by
protein electrochemistry.
Project 4: Structural signatures of P450s (with Dr. Mikael Boden)
We are using bioinformatics tools to explore the essential sequence and structural features underpinning
all ~12000 known P450s so as to determine how P450s work.
Students doing Honours in the Gillam lab gain experience in cutting-edge techniques such as artificial
evolution of proteins, high throughput screening, protein design and preparation of nanodiscs as well as
fundamental methods of molecular cloning, protein chemistry, enzymology and metabolite analysis.
Our research suits students in biochemistry/molecular biology, chemistry, biotechnology, or bioinformatics
who are interested in discovering how enzymes work and how to engineer them to provide clean green
alternatives to chemical processes.
43
SCMB Biotechnology Research Projects 2016 | Individual Contributors
PROFESSOR JEFF GORMAN
Queensland Institute of Medical Research (QIMR)
Phone: 07 3845 3669
Email: [email protected]
Protein Discovery / Proteomics
The QIMR Protein Discovery Centre is arguably the most advanced infrastructure centre in Australia for the
analysis of chemical features of proteins and documentation of proteomes of cells, organisms and tissues.
We are particularly interested in the interactions between host cells and infectious organisms as reflected
by dynamic changes in the protein repertoires (proteomes) of cells infected by viruses. We are also
interested in interactions between proteins required to initiate, sustain and perpetuate viral and parasitic
invasion of cells. The ultimate aim of our work is to develop a better understanding of interactions between
infectious organisms and host cells to develop therapeutic interventions for serious human diseases such as
viral respiratory infections and malaria. Our projects involve extensive collaborations with leading
Australian and international scientists.
Evasion of host cell innate immunity by respiratory syncytial virus: Respiratory syncytial virus (RSV) is a
serious pediatric respiratory pathogen and is increasing recognised as an important pathogen of geriatrics.
RSV is a master of evasion of the host cell antiviral response. One specific viral gene product, non-structural
protein 1 (NS1) of RSV contributes substantially to blocking the host cell antiviral response. In this project
we are using a combination of reverse viral genetics and proteomics to determine the mechanism(s) by
which NS1 exerts its influence over the infected cell. This project involves collaboration with Dr Peter
Collins and his group from the US National Institutes of Health and Dr Kirsten Spann from UQ who
contribute molecular virology expertise.
Click chemistry probes of complex macromolecular assemblies: This project involves the development of a
diverse range of click chemistry probes to label the exterior of macromolecular assemblies. These probes
are designed to probe the distributions of protein domains within membrane assemblies and to obtain low
resolution structural information on externally disposed domains. These probes will be applied to help
understand the interactions of viruses and parasites with host cells and the structures of proteins on the
surfaces of these infectious agents. This project involves collaboration with Dr Ross McGeary of UQ and
scientists from QIMR, including Dr Kathy Andrews (malaria parasites), Dr Greg Anderson (iron transport)
and Dr Nathan Subramaniam (iron transport).
Viral proteomics: Using proteomic techniques, we and others have shown that viruses often package
cellular proteins into mature virions. These cellular proteins are often from molecular machines that viruses
use during trafficking in and budding from the host cell. This project aims to investigate the variation in
cellular proteins packaged by different viruses in order to ascertain the likely mechanisms by which
different viruses interact with host cell molecular machinery.
Post-translational modifications of malarial proteins: Malaria transitions through a number of different
forms during its lifecycle. This project aims to examine the post-translational modifications to malarial
proteins, particularly phosphorylation, during these transformations as a way of defining these processes at
a molecular level. This is a collaboration with Dr Don Gardiner and his group at QIMR.
44
SCMB Biotechnology Research Projects 2016 | Individual Contributors
PROFESSOR PETER GRESSHOFF
ARC Centre for Integrative Legume Research
Phone: 07 3365 3550
Email: [email protected]
Plants possess stem cells that have the ability to differentiate into multiple cell types. The signals
controlling this process are critical in the developmental biology of plant growth (see Beveridge et al, 2007;
Curr. Topics in Plant Biology). We are looking at one specific stem cell cluster called the nodule meristem.
These develop into new organs. We ask: what are the genes responsible for that? How do they interact?
What are the signals and the receptors? How does physiology interact with gene expression? We offer
three cutting edge projects for top students willing to learn functional genomics and plant biotechnology.
The research is carried out within the ARC Centre of Excellence for Integrative Legume Research (CILR), and
interested students should visit the website www.cilr.uq.edu.au.
Project 1: Molecular signalling during stem cell differentiation and lateral organ differentiation in legumes
such as soybean, Lotus japonicus and Medicago truncatula): The project utilises our increasing
understanding of long distance regulation of plant organ induction and differentiation. Critical genes
controlling nodulation (GmNFR1, GmCLE80, GmNARK) have now been cloned and characterised. We are
starting to understand what molecular signal activates the receptor kinase, what are the down-stream
signals and responses (Kinkema and Gresshoff, 2008, Mol. Plant Microbe Interactions), what are its ligands,
what proteins are phosphorylated? (See Miyahara et al, 2008, J. Biol. Chemistry). We recently discovered
new peptide signal molecules that may act like hormones (Gresshoff et al, 2009, Plant Signalling &
Behaviour). We are testing the similarities of these regulatory circuits with those controlling stem cell
proliferation (i.e., GmCLV1, GmWUS, GmCLV2, and GmCLV3). Supervisors: Professor Peter Gresshoff, Dr
Arief Indrasunumar, Dr Jacqui Batley and Dr Brett Ferguson.
Project 2: Biotechnology of sustainable biofuel (biodiesel) production from the legume tree Pongamia
pinnata: Biofuels are essential for our future. We have initiated a biofuel program using biotechnology and
genetics coupled with physiology and biology to develop a scientific basis for that growing industry. We are
focusing on a legume to eliminate the energy and environmental costs of nitrogen fertiliser. Our plant of
choice is a legume tree Pongamia pinnata (see Scott et al, 2008, BioEnergy Research) from which oil-rich
seeds are harvested each year. Already industry such as ORIGIN Energy, Pacific Renewable Energy, and
BioEnergy Research, are interested in this biotech project. Several projects exist dealing with the
optimisation of nitrogen fixation, seed storage protein gene promoters, gene expression analysis, etc.
Supervisors: Dr Paul Scott, Professor Peter Gresshoff, Dr Bandana Biswas, and Dr Qunyi Jiang and.
Project 3: Molecular physiology and biotechnology of ethylene regulation of nodulation and lateral root
development in the model legume Lotus japonicus: This legume has a small genome, is easily transformed,
and has yielded many valuable mutants. Forward and reverse genetics are available. We have produced the
world’s first transgenic legumes expressing an Arabidopsis ethylene receptor gene (see Lohar et al, 2009,
Annals of Botany; Gresshoff et al, 2009, Plant Signaling & Behaviour). Furthermore we have isolated both
ethylene and ABA insensitive mutants in this model legume. The ethylene insensitive plants have altered
physiological properties including increased nodulation, decreased lateral root formation and slowed
maturation. The ABA insensitive mutant BEYMA shows extreme wilting because of an inability to regulate
stomatal openings (see Biswas et al, 2009, Molecular Plant). Cloning of the BEYMA gene is an immediate
goal. We are attempting to eliminate some of the negative effects by using tissue-specific promoters in
transformation. Grafting is needed to evaluate the role of shoot vs. root in the physiological stress
responses. Supervisors: Professor Peter Gresshoff, Dr Bandana Biswas and Dr Qunyi Jiang
45
SCMB Biotechnology Research Projects 2016 | Individual Contributors
DR ULRIKE KAPPLER
School of Chemistry & Molecular Biosciences
Phone: 07 3365 2978
Email: [email protected]
Regulation of gene expression
Regulation of bacterial sulfite oxidation – a novel role for extracytoplasmic function (ECF) sigma factors.
Enzymes & their role in bacterial physiology
Do metalloenzymes support virulence of human pathogens? Case study: Haemophilus influenzae
Molybdenum enzymes.
Friend or Foe? – Metabolic interactions between Streptococcus pneumoniae and Haemophilus influenzae.
Environmental microbiology & applications
Some like it alkaline – Can we use alikaliphilic sulfur oxidizers to treat sulfur pollution?
Co-supervision with Prof. Gordon Southam: “The growth of gold nuggets” – bacterial degradation of
thiosulfate gold complexes.
If you find these topics interesting, but would like to work on other aspects of the projects, please contact
me – this list is not comprehensive and additional projects are available.
46
SCMB Biotechnology Research Projects 2016 | Individual Contributors
PROFESSOR MARK KENDALL
Australian Institute for Bioengineering & Nanotechnology (AIBN)
Phone: 07 3346 4203
Email: [email protected]
DR SIMON CORRIE
Australian Institute for Bioengineering & Nanotechnology (AIBN)
Phone: 07 3346 4209
Email: [email protected]
Web: http://www.aibn.uq.edu.au/simon-corrie
Delivering vaccines and sampling diagnostic molecules through the skin
The outermost layers of our skin contain a rich and untapped source of immune-sensitive cells and bloodborne biomarkers. We are developing new technologies to deliver vaccines to, or extrac diagnostic
biomarkers from, these outer skin layers. Our group is a multidisciplinary mix of scientists (chemists,
immunologists, virologists, vaccinologists) and engineers (mechanical, civil, chemical) who together bring a
diverse array of expertise and skill sets to solve important technology problems and to learn more about
the biology, immunology and mechanical properties of the skin. Our laboratory facilities include a
mechanical design suite, a multi-photon microscopy system, a range of immunological and molecular
assays and material fabrication and surface modification facilities. We also use the facilities of the
Australian National Fabrication Facility QLD node (ANFF-Q – level 2 AIBN), UQ’s Centre for Microscopy and
Microanalysis (CMM – especially SEM, XPS) and the University of Queensland Biological Resources (UQBR)
animal housing facility (level 6, AIBN to support our manufacturing, analytical and pre-clinical testing
needs.
We currently have Honours project opportunities in both vaccine delivery and diagnostics projects. These
projects include:
• Engineering, expressing and testing novel vaccine formulations on patches in comparison to standard
intramuscular injections
• Engineering, expressing and testing new diagnostic capture probes for improved diagnostic performance,
based on sensitivity or assay simplicity
• New surface chemistry approaches to improve capture and release of biomolecules from patch devices
• Microfluidic approaches to detect key biomarkers extracted from skin
Projects are available for a wide array of skill sets. Students with a background in biotechnology, molecular
biology or physical/inorganic chemistry should apply. Skills gained will include molecular biological
techniques (ELISA/PCR), surface chemistry, microfabrication and pre-clinical animal testing of devices
(optional). Opportunities exist for students to continue their work, or start new projects, in MPhil or PhD
programs.
47
SCMB Biotechnology Research Projects 2016 | Individual Contributors
PROFESSOR ALEXANDER KHROMYKH
RNA Virology Laboratory
School of Chemistry & Molecular Biosciences
Phone: 07 3346 7219
Email: [email protected]
RNA virology laboratory study molecular mechanisms of virus RNA replication and virus-host interactions
with the main focus on the West Nile virus (WNV) and more recently on Chikungunya virus. WNV belongs
to Flaviviruses, a group of highly pathogenic positive strand RNA viruses causing major outbreaks of
potentially fatal diseases and affecting more than 50 million people each year. Chikungunya virus is a
member of Alphaviruses and has recently caused large outbreaks of devastating arthritis disease in Reunion
Island and Asian countries. We are aiming at a better understanding of how these viruses replicate in the
host and cause disease, which will help in the development of antiviral drugs. In addition, we develop and
evaluate vaccine candidates to prevent infection and outbreaks.
The following projects are available:
Role of Small Subgenomic RNA in Flavivrus Pathogenicity. We recently identified a small subgenomic RNA
produced from the 3’ untranslated region of the viral RNA in cells infected with a variety of flaviviruses. This
subgenomic flavivirus RNA (sfRNA) is the product of incomplete degradation of genomic RNA by cellular
ribonucleases and is required for viral response. We will elucidate the function of sfRNA in the viral life
cycle and identifyi cellular and viral interaction partners of sfRNA.
Virulence Determinants and Host Innate Immune Response to West Nile Viruses. We have shown
previously that WNV is able to evade innate immune response with more virulent strain able to do it more
efficiently. There are a number of projects available in collaboration with leading overseas groups (M
Diamond, USA; M Gale, USA; and S Akira, Japan) as well as local virologists (Roy Hall, SCMB) which will focus
on the mechanisms by which pathogenic (New York 99) and non-pathogenic (Kunjin) strains of WNV
interact with the host innate immune response and how these interactions determine outcome of
infection.
KUN Virus DNA-Based Vaccine against Pathogenic Flaviviruses. We recently published the development of a
highly effective DNA vaccine against WNV which involves the production of single round infectious particles
and has been shown to induce high antibody levels in mice and horses. The project will continue in
collaboration with Dr. Roy Hall at SCMB and Dr. Andreas Suhrbier at the QIMR to extend the technology to
development of vaccines against other medically important flaviviruses, dengue and Japanese Encephalitis.
The role of miRNAs in Flavivirus-Mosquito Host Interactions. In collaboration with S Asgari (SBMS) we have
identified a first miRNA produced by WNV and have shown that it targets a transcription factor in mosquito
cells that is essential for virus replication. This project is aimed at further investigations of the role of WNVinduced/produced cellular and viral microRNAs (miRNA) in determining the outcome of virus infection in
mosquito vector.
Innate immune response to Chikungunya virus. This project is a collaboration with Andreas Suhrbier (QIMR)
and is focused on understanding how the innate immune response to this infection relates to virus-induced
disease. Using mouse model of the disease developed at QIMR the studies will employ a wide range of
mouse strains deficient in expression of various factors involved in innate immune response and cell lines
derived from them to identify host factors involved in response to Chikungunya virus infection and in the
development of virus-induced arthritis
48
SCMB Biotechnology Research Projects 2016 | Individual Contributors
PROFESSOR GLENN KING
Institute of Molecular Biosciences
Phone: 07 3346 2025
Email: [email protected]
Venoms to drugs: translating toxins into therapeutics
We are interested in the evolution, structure, pharmacology,
and potential therapeutic applications of disulfide-stabilised
peptides from the venoms of centipedes and spiders. Our primary
focus is the discovery, structure-function characterisation, and
therapeutic development of venom peptides that modulate the
activity of neuronal ion channels involved in pain signalling in
humans. Molecules that antagonise these ion channels have
the potential to be developed as analgesics.
We are currently focussed on developing selective, high-affinity
blockers of three human ion channels—acid sensing ion channel (ASIC) 1a
and 3, and the voltage-gated sodium channel 1.7 (NaV1.7). Selective blockers
of the latter channel are likely to have broad utility against a wide range of
pain types since humans with loss-of-function mutations in NaV1.7 have a congenital inability to sense any
kind of pain without deleterious affects on any other sensory modalities except olfaction.
We have a collection of >300 arthropod venoms that can be used in high-throughput screens against ion
channels of interest. Using this approach, we showed that spider venoms are the best natural source of
NaV1.7 modulators with 35% of all venoms screened containing at least one blocker of this channel. We
have already purified 40 spider-venom peptides that block this highly sought after analgesic target. One
lead molecule has already progressed to preclinical studies in rodent pain models.
We recently discovered the most potent known blocker of human ASIC1a, which inhibits the channel with
an IC50 of 500 pM. This venom peptide has potential not only as an analgesic but also as a therapeutic
designed to ameliorate the neuronal injury often associated with ischemic stroke.
Current projects include:
1. Development of novel analgesic drugs based on spider-venom peptides
2. Development of novel anti-stroke therapeutics based on spider-venom peptides
3. Molecular evolution of spider and centipede venoms
Background reading
1. King GF (2011) Venoms as a platform for human drugs: translating toxins into therapeutics. Expert Opin.
Biol. Ther. 11, 1469–1484.
2. Vetter I, Davis JL, Rash LD, Anangi R, Mobli M, Alewood PF, Lewis RJ and King GF (2011) Venomics: a new
paradigm for natural-products-based drug discovery. Amino Acids 40, 15–28.
3. Escoubas P & King GF (2009) Venomics as a drug discovery platform. Expert Rev. Proteomics 6, 221–224.
49
SCMB Biotechnology Research Projects 2016 | Individual Contributors
PROFESSOR BOSTJAN KOBE
School of Chemistry & Molecular Biosciences
Phone: 07 3365 2132
Email: [email protected]
Structural Biology of Infection, Immunity and Molecular Recognition
The recognition of proteins by other proteins and ligands occurs in essentially every cellular process. We
are trying to understand this process at the structural level, focusing particularly on the processes of
infection and immunity. Our group is using an integrated approach combining determination of threedimensional structures (with major emphasis on X-ray crystallography) with computational techniques,
methods for quantitative evaluation of interactions such as the biosensor, protein chemistry and molecular
biology.
Project 1: Structural studies of proteins involved in innate immunity in mammals and plants
The aim of this project is to use structural biology to understand the molecular basis of processes involved
in the innate immune response in mammals and plants, with implications for infectious and inflammatory
disease, cancer and agriculture. The projects involve protein expression, purification, crystallization and
structure determination.
Project 2: Structural studies of proteins involved in bacterial pathogenesis
The aim of this project is to use structural biology to understand the processes of bacterial pathogenesis by
different bacterial pathogens. The projects involve protein expression, purification, crystallization and
structure determination.
Project 3: Understanding the mechanism and specificity of nucleo-cytoplasmic transport
The aim of this project is to understand the mechanism of transport of proteins into the nucleus, including
the specificity and regulation, with the long-term goal of manipulating this essential process. The projects
involve protein expression, purification, crystallization and structure determination, as well as
bioinformatics aspects.
Project 4: Linear motifs in signal transduction
Linear sequence motifs are recognized in many signalling processes, including protein kinases and phosphopeptide binding domains. The project currently has a computational focus on developing bioinformatic
tools that integrates structural information with sequence and other available data.
50
SCMB Biotechnology Research Projects 2016 | Individual Contributors
DR SHIH-CHUN LO (LAWRENCE)
Centre for Organic Photonics & Electronics
School of Chemistry & Molecular Biosciences
Phone: 07 3346 7657
Email: [email protected]
Organic materials and Nanotechnology
We are focusing on developing new classes of nanomaterials mainly for energy related applications, such as
photon-induced water splitting (for H2 generation), solar cells, and organic light emitting diode (OLEDs) as
well as bio-applications. Honours students will learn how to design, synthesise and characterise these
frontier functional materials.
Project 1: Clean hydrogen fuel generation
The use of hydrogen gas as a renewable and clean fuel has been one of the most
exciting research fields, in particular, direct hydrogen creation from water driven
by sunlight. Developing efficient and long-lasting water-splitting photosensitisers
and catalysts has been the key challenge for the technology. The project is to
synthesise and characterise new water-splitting photosensitizers for effective
light absorption and catalysts for efficient water decomposition.
Project 2: Advanced materials for opto-electronics (e.g., OLEDs, solar cells, and photodiodes)
The project is to develop new electro-active materials for OLEDs,
solar cells, and photodiodes for our next generation flat-panel
displays (e.g., mobile phones, tablets, monitor displays and TVs
for the superior display-quality and superb energy saving),
renewable energy generation and high-sensitive detectors. The
project will involve organic/organometallic and physical
chemistry, and students will learn how to fabricate and
characterise these devices by closely working with device physicists.
Project 3: Biomaterials for imaging and treatment
Photodynamic therapy (PDT) has been developed to provide non-invasive (compared with conventional
surgery) and less side effects (compared to
chemotherapy) for cancer treatment. PDT can
be accurately targeted, and repeatedly
administered
without
the
total-dose
limitations related with radiotherapy and result
in little or no scarring after healing. To facilitate
the advantages of PDT, we are developing
novel bio-compatible photodynamic therapy
agents for deeper tissue treatment with less
photodamage with effective two-photon
absorption activities.
51
SCMB Biotechnology Research Projects 2016 | Individual Contributors
DR PATRICIA LOPEZ-SANCHEZ
Centre for Nutrition and Food Sciences
ARC Centre of Excellence in Plant Cell Walls
Phone: 07 3346 7373
Email: [email protected]
Our research focuses on the relationship between the chemical composition-architecture and material
properties of cell walls in plants. The physical properties of the cell wall have direct implications for the use
of plant material in many technological fields such biomaterials for medical applications, agri-food industry,
paper production and environmentally friendly energy sources. Furthermore material properties are
relevant for many plant bioprocesses, for example the wall has to be rigid to withstand external and
internal forces and at the same time flexible enough to allow for growth and development of the plant.
These features make the plant cell wall an outstanding material.
Project 1: Structure-function of engineered cell walls: a way to broaden the biotechnological applications
of plant materials
This project will make use of model plant systems such as bacterium Gluconacetobacter xylinus which
produces pure cellulose in liquid fermentation. By using microbiological techniques and including chosen
cell wall polymers in the fermentation medium, a range of cellulose-based composites can be engineered
which have many properties remarkably similar to plant cell walls. Their materials properties will be
characterized using stress controlled rheometers, before and after being subjected to mechanical forces
(MPa) characteristic of the turgor pressure found in growing plants. With this approach, we aim to obtain a
first understanding of the molecular basis for plant cell wall properties under active turgor pressure. The
implications of such studies will contribute to the use of plant-based materials for food, pharmaceutical and
medical applications.
Project 2: Mimicking nature by using polysaccharides as building blocks for cereal endosperms walls
Cereals are one of the main components of the human diet worldwide. In their natural form, they are a rich
source of vitamins, minerals, carbohydrates (fibre), fats and protein. However, when refined the remaining
endosperm (‘white flour’) is mostly carbohydrates, such as starch enclosed by cell walls containing β-glucan
and arabinoxylan. Extraction of cell wall components disrupts the architecture of the wall, which is key in
determining its material properties. Therefore the development of models to mimic cell wall architecture is
highly relevant to study the underlying relationships between their composition, microstructure and
material properties. In order to build these cell wall analogues we will make use of enzymatic treatments
and cryogelation of polysaccharides, a method which uses freeze-thawing cycles to form physically crosslinked networks .The outcomes of the project will contribute to advancing scientific understanding of plant
cell wall biology to enable sustainable biomass production for food security and human health.
52
SCMB Biotechnology Research Projects 2016 | Individual Contributors
PROFESSOR ALAN E. MARK
Molecular Dynamics
School of Chemistry & Molecular Biosciences
Phone: 07 3365 4180
Email: [email protected]
Websites: http://profiles.bacs.uq.edu.au/Alan.Mark.html
http://compbio.chemistry.uq.edu.au/md/
The group uses computer simulation techniques to model the dynamic behaviour of biomolecular systems
such as proteins, nucleic acids and lipid aggregates. The simulation software and atomic force fields we
develop are used to understand processes such as how peptides fold and self-assemble into functional
complexes or how anti-microbial peptides enter cells. We look for students interested in working at the
interface between structural biology, chemistry, and computational science.
Possible projects include:
Project 1: The nucleation and growth of amyloid fibrils
Amyloid fibrils are self-assembled peptide aggregates associated with a
range of neurodegenerative diseases. Molecular dynamics (MD)
simulation techniques will be used to shed light on the structure and
formation of amyloid fibrils. In particular, simulations will be used to
identify the minimal stable structure required for fibril growth.
Project 2: The activation of the growth hormone receptor
The activation of cell surface receptors is a critical step in cell
regulation. MD simulations will be used to characterize the conformational changes that accompany the
binding of growth hormone to its receptor thereby shedding light on the mechanism of action of cytokine
receptors in general.
Project 3: Predicting protein-ligand interactions
Free energy calculations are a highly accurate but computationally expensive method for predicting binding
affinities. You will help refine and test a computationally efficient single-point free energy methodology
developed within the group for use in virtual drug screening.
The peptide Magianin interacting with a DPPC
bilayer showing the formation of a
transmembrane pore.
Project 4: Membrane protein assembly (antimicrobial peptides and viral fusion proteins)
Despite their importance, little is known about to
how membrane peptides and proteins assemble into
functional complexes. To investigate this we are
studying a range of small anti-microbial peptides that
spontaneously self-assemble within membranes
inducing pore formation, membrane fusion, or even
cell death. On a larger scale we are studying how
proteins of enveloped viruses such as Dengue and
Ebola drive the fusion of the viral and cell
membranes. This is a key step in the entry of the
virus into cells and a prime target for therapeutic
intervention.
53
SCMB Biotechnology Research Projects 2016 | Individual Contributors
PROFESSOR DANIEL MARKOVICH
Ion Transport and Cell Signalling
Molecular Biology and Biotechnology
School of Biomedical Sciences
Phone: 07 3365 1400
Email: [email protected]
Website: http://www.uq.edu.au/sbms/staff/professor-daniel-markovich
Membrane Transporters: Biochemistry, Molecular Biology and Physiology
Prof Daniel Markovich’s interests lie in the study of the biochemistry, (patho)physiology and genomics of
mammalian ion transporters, involved in transcellular movement of ions (sulfate, chloride, oxalate) across
epithelial cells. In the last few years, several membrane transporters have been cloned, characterised and
knock-out mice generated in his laboratory.
The following Honours/MPhil/PhD projects are currently available in his laboratory:
• Project 1: Biochemical roles of polymorphisms in human sulfate transporters
• Project 2: Trafficking of human sulfate transporters in mammalian cells
• Project 3: Second messenger pathways regulation of human sulfate transporters
Using modern molecular and cellular biological techniques, these projects study the molecular function and
regulation of ion transport systems by characterising their protein and mRNA expression in both in vitro (in
established cell lines) and in vivo (animal models, Xenopus laevis oocytes) systems. These studies will
elucidate the function and molecular regulation of these transporters in the body, which will help in
clarifying their roles in ion homeostasis, which will provide important insights into diseases associated with
membrane transport processes.
Selected Publications
Markovich D (2012) Slc13a1 and Slc26a1 KO models reveal physiological roles of anion transporters.
Physiology 27: 7-14
Markovich D (2011) Physiological roles of renal anion transporters Nas1 and Sat1. Am. J. Physiol.-Renal.
Physiol. 300: F1267-70
Dawson PA, Russell CS, Lee S, McLeay SC, van Dongen JM, Cowley DM, Clarke LA, Markovich D (2010)
Hepatotoxicity and urolithiasis in Sat1 transporter (Slc26a1) null mice. J. Clin. Invest. 120: 706-12
Markovich D and Aronson PS (2007) Specificity and regulation of renal sulfate transporters. Ann. Rev.
Physiol. 69:7.1-7.15
Dawson PA and Markovich D (2005) Pathogenetics of the human SLC26 transporters. Curr. Med. Chem. 12:
385-396
Dawson PA, Beck L and Markovich D (2003). Hyposulfatemia, growth retardation, reduced fertility and
seizures in mice lacking a functional NaSi-1 gene. Proc.Natl.Acad.Sci.USA 100 (23):13704-9
54
SCMB Biotechnology Research Projects 2016 | Individual Contributors
ASSOCIATE PROFESSOR FRED MEUNIER
Molecular Dynamics of Synaptic Function Lab
Queensland Brain Institute / School of Biomedical Sciences
Phone: 07 3346 6373
Email: [email protected]
The focus of our laboratory is to decipher the dynamics of molecular events taking place during nerve cells
communication and plasticity. Our ultimate aim is to understand the sequence of interactions underlying
neurotransmitter release and neuronal sprouting and to utilise this knowledge to design therapeutic
strategies for treating human diseases affecting the nervous system such as neurodegenerative diseases.
Examples of available projects are:
Project 1: Biotechnology to help treat motoneuronal diseases
Motoneuronal diseases are notoriously difficult to treat and one of the
main hindrances to treatment is the relative inaccessibility of
motoneurons. We are designing probes to deliver fluorescently-labelled
molecules specifically in motoneurons.
Project 2: Biotechnology to image dynamic events in living neurons
Design novel methods to investigate the neurons’ internal trafficking of
vesicles involved in nerve cell communication. This project will aim
designing new optical tools and methods for investigating vesicle
trafficking in living neurons.
55
SCMB Biotechnology Research Projects 2016 | Individual Contributors
ASSOCIATE PROFESSOR
CHAMINDIE PUNYADEERA
School of Biomedical Sciences /Institute of Health and Biomedical Innovations
Queensland University of Technology
Phone: 07 3138 0830
Email: [email protected]
Project 1: Early Cancer Detection using a Saliva Sample
Background: Cancer is the leading cause of death worldwide and accounted for 7.6 million deaths
(around 13% of all deaths) in 2008 (WHO, 2011 February Report). Tobacco use is a major risk factor for
head and neck cancer and lung cancers, and smoking kills over 1,000,000 people a year, causing 30% of
all cancer-related deaths in the western societies. The direct impact of smoking can clearly be seen in
the oral cavity due to its proximity, thus, human saliva is an ideal diagnostic medium for investigating
smoking-related cancers.
DNA methylation in cells is one of the earliest events that occur during cancer initiation and has
demonstrated considerable utility by enabling early disease detection, better disease stratification,
and predicting disease relapse and response to therapy in cancer and other diseases (Esteller, M.
Epigenetics in Cancer, New England Journal of Medicine, 358: 2008). We are developing cutting-edge
tools to diagnose cancer at an early stage, Changing Traditional Health Care Paradigm.
Project aims:
Identify and validate biomarkers in saliva for early detection and staging of head and neck cancers.
Benefits for you?
• You will have access to the state of the art facilities and will gain experience in working in a
multidisciplinary team, focused on cutting-edge science
• You will develop laboratory skills in molecular biology, cell cultures and biochemistry
• You will have an opportunity also work in hospitals
Project 2: Saving Hearts with a Simple Saliva Test
Background: Cardiovascular diseases (CVD) including heart, stroke and blood vessel disease, affect
about 3.67 million Australians. Every 10 minutes ONE Australian dies from CVD. An increase in CVD in
Australia is accelerated by growing as well as an aging population. Human saliva as a diagnostic medium
has gained attention in the last decade due to its non-invasiveness, easy sampling and lower threat of
transmitting infection. Human saliva is the window to our body and saliva mirrors biomarkers found in
blood. Up until now, there have been ~ 2000 proteins found in human saliva and about ~26% are also
present in blood, highlighting the importance of saliva for clinical research.
Project aims: To develop non-invasive low cost tools to detect heart disease at an early stage.
The Saliva Translational Research Team:
Our team is young, dynamic and vibrant, and is multidisciplinary. We are geared at investigating the
diagnostic potential of human saliva aimed at translating our research findings into a clinical setting.
Collaborators:
Professor Ian Frazer
Professor John Atherton
Professor Henry Krum (Monash University).
Professor James Herman (John Hopkins University, Baltimore, USA)
Professor Karam Kostner
Professor William B Coman
56
SCMB Biotechnology Research Projects 2016 | Individual Contributors
DR STEVEN REID
Deputy Director, Biotechnology Program
School of Chemistry & Molecular Biosciences
Phone: 07 3365 3991
Email: [email protected]
Research Area: Production of Baculovirus Biopesticides – A Systems Biology Approach
Increased resistance to chemical pesticides and concern over their use has renewed interest in the
application of biological means to control pests of commercial importance. Many wild type Baculoviruses
can specifically infect and kill key agricultural caterpillar pests and some virus strains can also target
mosquitoes.
The Reid laboratory has a process patent on a procedure for producing Baculoviruses via fermentation. The
lead product is a Baculovirus targeting the Helicoverpa pest species, which is responsible for a current
$US3.2 billion per annum market in traditional chemicals.
A baculovirus product manufactured by the Reid Group and formulated by Bioflexus has been registered
for use on Australian crops to combat heliothis caterpillars (more widely known as the cotton bollworm),
under the trade name of ‘Heliocide’. The Reid Group is undertaking further research to increase current
yields, to enable manufacture and evaluation in the niche Australian market.
Currently the Group is collaborating with Professor Lars Nielsen to use a Systems Biology approach utilising
transciptomic and metabolomic techniques in an effort to understand how the virus interacts with host
cells in culture. The team anticipates further increases in yield, making it cost effective in broader markets,
both national and international.
Specific Research projects:
Project 1:
Development of a Heliothis BACMID system for manipulation of the H.arm virus genome
(gene knockouts). This system will be used to generate altered viruses for further
transciptomic and metabolomic studies.
Project 2:
The use of Real Time PCR to quantify virus binding kinetics to enable optimisation of early
process steps for the manufacture of virus in vitro
Project 3:
Development of sample extraction procedures and appropriate HPLC/GC-MS techniques
for quantifying intracellular metabolite levels for infected and non infected cells in culture.
These procedures are essential to enable our metabolomic studies.
57
SCMB Biotechnology Research Projects 2016 | Individual Contributors
ASSOCIATE PROFESSOR
JOE ROTHNAGEL
School of Chemistry & Molecular Biosciences
Phone: 07 3365 4629
Email: [email protected]
Website: http://www.scmb.uq.edu.au/staff/index.html?page=142199
Development of the next generation of gene expression systems
A major focus of this laboratory is directed towards the development of new eukaryotic expression vectors.
We are investigating the role of post-transcriptional mechanisms in gene expression. This work has led to
the development of short cis-acting sequences based on small upstream open reading frames (uORFs) that
can be used to modulate gene expression; known as GeneDimmerTM and GeneBooster respectively. Both
GeneDimmerTM and GeneBooster expression vectors will ultimately be used in cell biology, gene therapy
and agriculture. Experiment procedures and approaches include bioinformatics, gene cloning and analysis,
cell culture, transgenic plants, and expression analysis.
The development of nucleus - targeting tags for the delivery of gene medicines
We have identified a peptide sequence that localises to the nucleolus. We are developing a series of
constructs that contain this peptide tag and are evaluating its use in delivering gene medicines to the
nucleus. This methodology has the potential to increase the concentration of these genetic constructs in
the nucleus thereby increasing their efficacy. We are also developing non-peptide aptamers of this
sequence.
Biotech Honours Projects will be offered in the following areas:
• Development of second generation GeneDimmerTM vectors and their characterisation in eukaryotic cells.
• Characterisation of novel small peptides encoded by sORFs (with Ross Smith & Amanda Nouwens)
58
SCMB Biotechnology Research Projects 2016 | Individual Contributors
PROFESSOR MARK SCHEMBRI
School of Chemistry & Molecular Biosciences
Phone: 07 3365 3306
Email: [email protected]
The common research theme in my laboratory is the study of surface proteins that mediate adhesion,
aggregation and biofilm formation by bacterial pathogens. Adhesion is the primary mechanism by which
bacteria colonize host tissue surfaces and initiate disease. My research deals primarily with pathogenic
Escherichia coli that cause intestinal and extra-intestinal infections. A major focus is uropathogenic E. coli
where we study the role of adhesins and other surface components in the development of biofilms and
colonisation of the urinary tract. Biofilms are microbial communities characterized by cells that are
irreversibly attached to a substratum or interface or to each other. Biofilms are of immense significance in
medical, industrial and environmental settings and this area of study has enormous scope and importance
in the field of bacterial pathogenesis. My laboratory also investigates mechanisms of adhesion and biofilm
formation by other pathogens including Acinetobacter baumannii, Klebsiella pneumoniae and Enterobacter
species.
Project 1. E. coli is the primary cause of urinary tract infection (UTI) in the developed world. It is estimated
that one in four women and one in twenty men will develop a UTI in their lifetime. The aim of this project is
to study the molecular characteristics of recently emerged multidrug resistant uropathogenic E. coli strains.
The project will employ forefront molecular techniques including genome sequence analysis, proteomics,
mutagenesis and cloning to characterise multidrug resistant strains and dissect their virulence capacity.
Project 2. Autotransporter proteins represent a major group of Gram-negative bacterial secreted proteins
that contribute to uropathogenic E. coli mediated UTI. Autotransporter proteins possess a range of
virulence properties such as adherence, aggregation, invasion and biofilm formation. We recently
characterised a novel translocation and assembly module that promotes efficient secretion of
autotransporter proteins across the outer membrane and published this in collaboration with other
research groups in Nature Structural & Molecular Biology. Recent genome sequencing of several
uropathogenic E. coli strains has also identified a number of previously uncharacterised autotransporter
proteins and we are currently trying to understand their contribution to virulence. This study aims to
characterise some of these genes and their products, study their mode of translocation across the outer
membrane and evaluate their role in adhesion, colonization and biofilm formation.
Project 3. Colonization of the bladder by uropathogenic E. coli results in the formation of intracellular cell
aggregates encased in a polysaccharide-rich matrix (i.e. a biofilm). These structures enable the bacteria to
cause chronic, persistent infections. Biofilm formation on medical implants such as catheters is also a major
source of recurrent infection and resistance to antibiotics. This project will examine the role of several
putative virulence factors (including uncharacterised fimbrial adhesins) from uropathogenic E. coli that are
associated with biofilm formation.
Project 4. Klebsiella are frequent causes of nosocomial infections; it is estimated that they account for 8%
of all hospital acquired infections in the western world. Next to E. coli infection, Klebsiella is the most
common cause of Gram-negative septicemia with a fatality rate of 25-50%. In the majority of bacteremic
cases, the focus of infection is the urinary tract. This project will identify and characterize novel virulence
factors from Klebsiella pneumoniae.
59
SCMB Biotechnology Research Projects 2016 | Individual Contributors
DR HORST JOACHIM SCHIRRA
Centre for Advanced Imaging
Phone: 07 3346 0360
Email: [email protected]
NMR-based metabonomics in clinical applications and environmental science (3 projects)
We try to solve the puzzle of metabolic pathways with NMR metabonomics. NMR metabonomics is the
newest frontier technology in systems biology. It analyses biological or clinical samples, such as cell
extracts, urine, and blood, by looking at the global composition of body fluids. We want to identify
systematic patterns or metabolic fingerprints that are associated with diseases, specific physiological
states, environmental or genetic conditions. Diseases and related conditions, as well as environmental or
genetic changes lead to global metabolic changes that are reflected in the composition of biofluids and can
thus be identified. These changes can then be used as diagnostic markers for identifying individuals at risk,
for identifying successful intervention strategies, and for following and monitoring treatment in patients.
The technique is powerful, as it can identify trends and metabolic changes that could be missed by a
narrow approach of screening only select metabolites or metabolite classes. We study metabolic changes
by investigating the chemical composition of biofluids with NMR spectroscopy. Changes in the metabolic
profile of e.g. urine are studied by multivariate statistical analysis and let us pinpoint, which parts of the
organism’s metabolism are disturbed. Thus, by understanding how disease affects the metabolism of an
individual and by understanding the metabolic consequences of a disease we might learn something about
the mechanism of a particular disease itself. I have several projects available in this area, focussing on a
variety of model diseases.
Current projects involve the study of the effects of growth hormone receptor mutations in mice, the
mechanism of phosphine resistance in C. elegans, as well as several projects aimed at developing NMR
metabonomics as a tool for clinical diagnosis. Some of our animal model systems are very well understood,
and in these cases we are trying to take the next step by investigating the connection between genotype
and phenotype on a systematic level. The practical use of NMR metabonomics involves the analysis of a
multitude of NMR spectra and correlation of these data with other data from physiology, biochemistry, or
clinical assessments. This multimodal analysis is at the cutting edge of systems biology and requires the
development of novel analytical tools and techniques. Thus, students with an interest or background in
mutivariate statistics, programming and/or bioinformatics are highly welcome in this environment, apart
from students with experience in chemistry and/or biochemistry.
Individual Projects: Three main projects in NMR-based metabonomics are available in 2010: One project
centres on the early detection of Prostate Cancer and will be conducted in collaboration with Prof Frank
Gardiner (UQ Centre for Clinical Research/Royal Brisbane and Women’s Hospital). The second project
focuses on oral diseases and their contribution to the total inflammatory burden of a patient, and will be
conducted in collaboration with Dr Pauline Ford (School of Oral Biology/Prince Charles Hospital). The third
project aims to close the gap between genotype and phenotype by characterising a cohort of mice with
mutations in the growth hormone receptor that leads to late-onset obesity. This project is in collaboration
with Prof Mike Waters (IMB) and Prof Lars Nielsen (AIBN). All projects will be conducted in SCMB using the
extensive NMR infrastructure of the Centre for Magnetic Resonance and the Institute for Molecular
Bioscience. The potential for follow-on PhD projects exists, depending on successful APD scholarships.
60
SCMB Biotechnology Research Projects 2016 | Individual Contributors
DR BENJAMIN SCHULZ
School of Chemistry & Molecular Biosciences
Phone: 07 3365 1892
Email: [email protected]
Molecular Systems Glycobiology
My research focuses on the mechanisms, biological roles and applications in biotechnology of glycosylation,
the most abundant and complex post-translational modification of proteins. Glycosylation is important in
biological processes such as human development, cancer and microbial infection. This is because
glycosylation is essential in biological activities as diverse as protein folding, fine-tuning protein enzymatic
activity and determining protein-protein interactions. Half of all proteins are glycosylated, and a single
protein can be modified by hundreds of different sugar moieties. The diversity of glycoproteins therefore
requires that we take a systems biology approach in our research. We aim to understand the mechanisms
controlling glycosylation in these various systems to develop diagnostics, therapies, vaccines and
applications in biotechnology.
Project 1. Engineering glycoproteins for improved expression
Many proteins currently used as pharmaceuticals or in biotechnology are glycoproteins, such as
erythropoietin (EPO) and monoclonal antibodies. These glycoproteins are generally made using expensive
mammalian cell expression systems. We have developed and filed a patent for a technology that involves
minimal modification of the amino acid sequence of a glycoprotein, which then allows the protein to be
expressed in low-cost bacterial expression systems. This project will further develop this technology using
site-directed mutagenesis, protein expression, purification and characterization.
Project 2: Drug resistance and N-glycosylation in breast cancer
Docetaxel is an important chemotherapeutic drug for treatment of breast cancer. However, it is very
common that tumours develop resistance to docetaxel. Recent studies have shown that the cellular
pathway of protein glycosylation is important in the development of docetaxel resistance. This study seeks
to understand how these cellular changes allow tumours to become resistant to docetaxel. This project will
use cell culture, mass spectrometry proteomics and bioinformatics.
Project 3: Bacterial glycoengineering
It was recently reported that some bacterial pathogens, including Haemophilus influenzae, encode systems
for cytoplasmic protein N-glycosylation. This project will use in vitro protein biochemistry and a nonpathogenic E. coli in vivo system to investigate the mechanisms of this process and its potential applications
in biotechnology.
61
SCMB Biotechnology Research Projects 2016 | Individual Contributors
ASSOCIATE PROFESSOR
CONRAD SERNIA
School of Biomedical Sciences
Phone: 07 3365 3180
Email: [email protected]
Endocrinology of Angiotensin
Angiotensin is a small peptide hormone that is commonly associated with blood pressure and salt balance.
Two widely prescribed classes of antihypertensive drugs are based on interference with Angiotensin action:
the angiotensin receptor antagonists (eg. Losartan) and angiotensin-converting enzyme inhibitors (eg.
Captopril). This lab is interested in uncovering links between angiotensin and degenerative diseases that
may be consequential to, or independent of, cardiovascular effects.
The current focus is on Alzheimer’s Disease, Oxidative Stress and Osteoporosis.
Project 1:
Project 2:
Project 3:
Alzheimer’s Disease: angiotensin regulation of amyloid precursor protein (APP) in neurones
Osteoporosis: angiotensin action on osteoblasts with particular emphasis on RANKL/OPG
regulation.
Involvement of angiotensin-mediated oxidative stress in (1) and (2) above.
Collaboration:
The laboratory collaborates with Prof Lindsay Brown (USQ); Prof Wally Thomas (UQ) and Prof Po Leung
(Chinese University of Hong Kong).
Research Techniques:
General endocrine methods, cell culture, molecular techniques.
Selected Publications:
SERNIA C. A critical appraisal of the intrinsic pancreatic angiotensin-generating system. J Pancreas 2:5055. 2001
Leung PS SERNIA C. The renin-angiotensin system and male reproduction: new functions for old hormones.
Molec Cell Endocrin 30: 263-70, 2003
Sernia, C., Tang, Z., Kerr, D., & Wyse, B. (1997) Novel perspectives on pituitary and brain angiotensinogen.
Front. Neuroendocrin. 18(2): 174-208.
Wyse, B. & Sernia, C. (1997) Growth hormone regulates AT1a angiotensin receptors in astrocytes.
Endocrinol. 138: 4176-4180.
Greenland K SERNIA C. Oestrogenic regulation of brain angiotensinogen. J Neuroendocrin 16: 508-515,
2004.
SERNIA C Huang H et al. (2007). Bone Homeostasis: an emerging role for the renin-angiotensin system. In
“Proteases of the rennin-angiotensin system in Human Disease” ed. P.Leung, Springer Verlag, pp263-287.
62
SCMB Biotechnology Research Projects 2016 | Individual Contributors
DR YASMINA SULTANBAWA
Queensland Alliance for Agriculture and Food Innovation (QAAFI)
Phone: 07 3276 6037
Email: [email protected]
[email protected]
Project 1: Antimicrobial efficacy of Leptospermum polygalyfolium honey with different levels of
methylglyoxal contents against MRSA and Pseudomonas
Recent studies on Leptospermum polygalifolium a myrtle native to Australia has shown antibacterial
activity against Methicillin-Resistant Staphylococcus aureus (MRSA), Staphylococcus aureus and Escherichia
coli (Sultanbawa and Smyth 2010). The most extensively studied leptospermum species is Leptospermum
scoparium ((Cooper, Molan et al. 1999; Henriques, Jenkins et al. 2010)) and this is the source of the well
known bioactive honey manuka from New Zealand. The honey from Leptospermum polygalifolium which is
harvested by the bees from a monofloral source and is only found in Australia could be branded and
marketed in a similar manner to the manuka honey. However, scientific evidence for the use of the
Australian honey for wound infections is limited and more studies are needed to prove efficacy.
Methylglyoxal (MGO) one of the phytochemicals present in this honey has been identified as one of the
chemical components responsible for antimicrobial activity ((Adams, Boult et al. 2008; Mavric, Wittmann et
al. 2008; Adams, Manley-Harris et al. 2009)). MGO levels of 1.1 – 1.8 mM in Leptospermum scoparium has
indicated antibacterial activity ((Mavric, Wittmann et al. 2008)). Our studies indicate higher levels of MGO
in honeys from Leptospermum polygalifolium. The aim of this project is to understand the mechanisms
that govern the antimicrobial activity of this honey at different levels of MGO ranging from 300 – 1750
mg/kg against MRSA and Pseudomonas aeruginosa.
Project 2: Determining the inhibitory effects of Leptospermum polygalyfolium honey on biofilms of
MRSA and Pseudomonas.
Honey is well known for its wound healing properties and one of the contributing factors is the
antibacterial activity in honey. With the increase use of antibiotics in medicine there has been a rise in
prevalence of antibiotic resistance bacteria such as MRSA. As a result there has been an urgent need to find
alternative antimicrobial strategies which include bioprospecting for natural sources and also changing the
methods used to elucidate antimicrobial activity. Honey as a natural antimicrobial is important as it has a
potent in vitro activity against antibiotic resistant bacteria and it has been successfully used in the
treatment of chronic wound infections not responding to antibiotic treatment.
Information on the antimicrobial activity of the Australian honey Leptospermum polygalifolium and
mechanisms that are responsible for inhibiting quorum sensing signals which in turn affect the growth of
biofilms will contribute to scientific evidence for the use of honey as a conventional and natural treatment.
The aim of this study is to understand the inhibiting effects of Leptospermum polygalifolium in the
formation of biofilms from MRSA and Pseudomonas.
63
SCMB Biotechnology Research Projects 2016 | Individual Contributors
DR KATE STACEY
School of Chemistry & Molecular Biosciences
Phone: 07 3365 4640
Email: [email protected]
Recognition of Cytosolic DNA as a Danger Signal
The DNA of eukaryotic cells is contained within a membrane-bound nucleus, and the appearance of DNA
within the cytosol indicates a danger to the cell. Cytosolic DNA can result from viral and bacterial infections
or the activity of endogenous retroviruses within the human genome. Responses to cytosolic DNA include
production of the anti-viral protein interferon-beta, and cell death. We identified AIM2 as a receptor for
cytoplasmic DNA eliciting cell death. AIM2 initiates formation of an “inflammasome” which is a protein
complex leading to activation of the protease caspase-1 and lytic cell death. We have recently shown that
AIM2 recognition of DNA also recruits and activates caspase-8, which leads to the death of cells by
apoptosis. Although the AIM2 pathway is only found in mammals, we find that chicken and insect cells can
also die after introduction of DNA into the cytosol. Consequently we propose that defences against
invading DNA are essential for defending against infections and guarding the genome of all multicellular
organisms. Future studies will focus on:1) Characterisation of the role of DNA detection in combatting viral infections
2) Definition of pathways of recognition of foreign DNA in non-mammals
3) Characterisation of the inflammasome complex induced by AIM2, and novel death-domain interactions
involved in recruitment of procaspase-8
4) Investigation of the role of AIM2 (absent in melanoma 2) as a tumour suppressor
Inflammasome Deficiency in Autoimmune Disease
The human autoimmune disease lupus involves formation of antibodies against self molecules and their
deposition as immune complexes in tissues. Inflammasomes lead not only to cell death but also to release
of the inflammatory cytokine IL-1b. Although most researchers have assumed that inflammasome
pathways will be elevated in autoimmunity, we find the opposite; in a mouse model of lupus there is
profound deficiency of three different types of inflammasome structures. We propose this leads to an
altered response to commensal organisms and poor clearance of pathogens, and promotes autoimmunity.
Projects will include:
1) Establishing the molecular basis for inflammasome deficiency in the mouse
2) Investigating whether human lupus patients have inflammasome deficiency
Relevant Publication:
Roberts, T.L., Idris, A., Dunn, J.A., Kelly, G.M., Burnton, C.M., Hodgson, S., Hardy, L.L., Garceau, V., Sweet,
M.J., Ross, I.L., Hume, D.A., Stacey, K.J. (2009) HIN-200 proteins regulate caspase activation in response to
foreign cytoplasmic DNA. Science 323:1057-1060.
64
SCMB Biotechnology Research Projects 2016 | Individual Contributors
DR MATT SWEET
Institute for Molecular Bioscience
Phone: 07 3346 2082
Email: [email protected]
Project 1: Targeting Histone Deacetylases in Inflammation
Acetylation of lysine side chains on proteins regulates diverse cellular processes including signalling,
transcription and protein targeting. Histone deacetylases (HDACs) are a family of enzymes that deacetylate
lysine side-chains, and inhibitors of these enzymes have efficacy as anti-cancer agents. HDAC inhibitors also
display anti-inflammatory properties. This project will investigate the role of specific HDACs in regulating
inflammatory responses of macrophages.
Project 2: Characterizing Human-specific Inflammatory pathways
Mice are routinely used in immunological models to study disease processes. Specific immune responses
are not necessarily conserved between mice and humans however, because the innate immune system is
under strong evolutionary pressure. Using expression profiling, we have identified innate immune genes
that have conserved regulation between mice and humans, as well as those that are divergent. This project
will explore the function of innate immune genes that display human-specific regulation.
65
SCMB Biotechnology Research Projects 2016 | Individual Contributors
PROFESSOR STEPHEN TAYLOR
School of Biomedical Sciences
Phone: 07 3365 3124
Email: [email protected]
Drug Discovery and Development
A major problem in clinical medicine is the effective treatment of many cruel diseases. Many of the worst
human ailments concern disorders of the immune and inflammatory systems, where the body seemingly
attacks its own tissues. The treatments for these kinds of disorders are limited, or toxic, or just plain
ineffective. Some of these diseases can kill in just a few days, some may slowly kill or disable over years or
even decades. The human suffering is incalculable and progress seems negligible.
In Dr Taylor’s laboratory, new classes of anti-inflammatory drugs are being developed, in collaboration with
chemists at the IMB (Professor David Fairlie’s group). We have successfully discovered and developed
orally active complement C5a antagonists and phospholipase A2 inhibitors. The C5a antagonist project has
led to the formation of the spin-off company, Promics Pty Ltd, and the filing of several key patents.
Projects are available for students to work on the preclinical pharmacology of lead compounds or with new
analogues. The work entails cellular, biochemical and whole animal studies, and is aimed at determining
the pharmacological activity of these new agents.
66
SCMB Biotechnology Research Projects 2016 | Individual Contributors
DR HANG TA
NHMRC Early Career Fellow (Whittaker Group)
Australian Institute for Bioengineering & Nanotechnology
Phone: +61 7 33463851
Email: [email protected]
Novel approaches in diagnosis and treatment of cardiovascular disease
Did you know that cardiovascular disease is Australia’s greatest health problem. It kills more people than
any other disease and creates enormous costs for the health care system. It places a heavy burden on
individuals and the community due to resulting disabilities. Atherosclerosis is the major cause of ischemic
heart disease which is the most common form of cardiovascular disease and the leading cause of sudden
death, accounting for 34% of all death in Australia in 2008. Despite primary and secondary prevention,
thrombotic and embolic events such as myocardial infarction and stroke remain a major health issue and
are leading causes of mortality and morbidity in Australia and worldwide.
Currently, the detection of these diseases is limited due to the lack of sensitive imaging methods and it
usually involves invasive procedures. Our group is working on different approaches to improve diagnosis
and treatment of these diseases. We are located within Australian Institute for Bioengineering and
Nanotechnology (AIBN) and has access to state-of-the-art facilities in bioengineering/biotechnology and
nanotechnology. AIBN offers a dynamic research environment and is home to world-class researchers
working at the interface of the biological, chemical and physical sciences. Current projects available include:
1. Smart magnetic resonance imaging nano-sensor for detecting and grading diseases
The early detection and accurate characterization of life-threatening diseases such as cardiovascular
disease and cancer are critical to the design of treatment. This project will develop smart magnetic
resonance imaging nano-sensors that can not only detect, but also sense and report the stage or
progression of cardiovascular diseases such as thrombosis, the leading cause of death in Australia and
worldwide.
2. Bifunctionalised nano-agents for simultaneous diagnosis and treatment of cardiovascular diseases
Cardiovascular disease is the major cause of mortality and morbidity in developed countries. It kills one
Australian every 12 minutes. Unstable vulnerable atherosclerotic plaques can rupture and cause
thrombosis, resulting in acute coronary syndromes, myocardial infarction and stroke. This project aims to
develop targeted smart nano-agents that can image vulnerable plaques and thrombosis; and
simultaneously provide anti-thrombotic activity.
3. Anti-inflammatory imaging nanomaterials for theranostics of diseases
Inflammation is part of the complex biological response of body tissues to harmful stimuli, such as
pathogens, damaged cells, or irritants. Chronic inflammation might lead to a host of diseases, such as hay
fever, periodontitis, atherosclerosis, rheumatoid arthritis, and even cancer. This project will investigate
novel approaches to develop nanomaterials which combine both therapeutic and diagnostic capabilities for
inflammatory diseases in one dose.
67
SCMB Biotechnology Research Projects 2016 | Individual Contributors
DR SIMON WORRALL
School of Chemistry & Molecular Biosciences
Phone: 07 3365 4626
Email: [email protected]
Mechanisms of Drug-Induced Tissue Injury
Liver, muscle, heart and brain injury have long been associated with the abuse and clinical use of drugs.
My research interests focus on ethanol, perhaps the most commonly abused drug. Ethanol is widely
tolerated but induces tissue injury in a small number of individuals. The potential research projects listed
below will investigate immunological and genetic phenomena associated with alcohol-induced tissue injury.
The potential projects available are:
1. Studies on the aetiology of ethanol- induced tissue injury to liver, skeletal and cardiac muscle, and brain?
2. Is protein modification by ethanol metabolites involved in the aetiology of:
a. Alcoholic liver disease?
b. Alcoholic skeletal and cardiac myopathy?
c. Alcoholic brain injury (with Peter Dodd)?
3. Novel protein modifications induced by ethanol metabolism (with Craig Williams, chemistry)
4. Discovery of molecular markers for the severity of Alzheimer’s disease.
(Top):A reaction scheme showing the formation of
malondialdehyde-acetaldehyde adducts.
(Left):Expression of GFP-tagged human keratin 18 in a primary rat
hepatocyte.
68
SCMB Biotechnology Research Projects 2016 | Individual Contributors
PROFESSOR PAUL YOUNG
Head of School
Virology Unit
School of Chemistry & Molecular Biosciences
Phone: 07 3365 4646
Email: [email protected]
Dr Young’s group is focused on the molecular biology and immunopathology of viral infections. The primary
goals of this research are to gain a clearer understanding of the pathogenesis of severe disease as well as
the development of novel vaccine and anti-viral strategies for the control of infections and improved
molecular diagnosis. Our laboratory has expertise in the areas of molecular biology, cell biology, structural
biology, protein biochemistry and immunology. Additional projects are likely to be available on discussion.
Project 1-Development of a dengue virus DNA vaccine based on a novel chimeric form of an
immunogenic viral protein.
We have been investigating sub-unit and DNA based vaccine strategies for the dengue viruses for some
years. Many of these have been based on expression of the immunogenic NS1 protein and we have
successfully demonstrated sold protection against viral challenge using a prime-boost approach using a
combination of DNA and recombinant sub-unit protein. We wish to expand our array of immunogenic
species through the inclusion of a novel chimeric construct that would provide protection against all four
serotypes of dengue virus. The project will involve the PCR amplification, cloning and expression as a single
fusion protein of domains from all four dengue virus serotypes. Both E.coli and recombinant baculovirus
expression will be examined. If time permits, the expressed product will be trialled in a vaccine/challenge
study.
Project 2-Development of a novel epitope tagging system for purification of recombinant fusion proteins.
This project would suit a student interested in biotechnology applications of molecular biology. We have
identified the linear amino acid sequences recognized by a series of high affinity monoclonal antibodies.
We want to test whether the fusion of these short peptide epitopes to foreign proteins can aid in their
purification via immuno-affinity chromatography – a well established tool in biotechnology research and
development. These epitopes are derived from the dengue virus NS1 protein and the student will be
involved initially in generating reporter gene constructs fused to these epitopes in order to examine their
suitability as epitope tags. Further studies with defined foreign genes will be examined time permitting.
Project 3-Site-directed mutagenesis and recombinant expression of the dengue virus NS1 protein.
The NS1 protein of dengue virus is essential for the replication of the virus at the RNA level. It is also
secreted from infected cells and is the target of a protective immune response. Paradoxically, it also
appears to be directly involved in the pathogenesis of infection. We have 132 been studying the structure
and biophysical features of NS1 for some time in order to help elucidate its exact function and these studies
are ongoing. This project will fit in with these studies and involve the cloning and expression of subdomains of NS1 as well as site-directed mutagenesis to identify key residues involved in the cell membraneassociation that is thought
69
SCMB Biotechnology Research Projects 2016 | Individual Contributors
DR ADRIAN WIEGMANS
Queensland Institute of Medical Research (QIMR)
Phone: 07 3362 0339
Email: [email protected]
Deciphering the molecular mechanisms of metastasis to design new-targeted therapies for breast cancer.
The transformation of normal breast tissue to tumor requires the accumulation of mutations, which is
readily achieved by deregulation of DNA repair pathways. We found that metastatic breast cancers have
high levels of the DNA repair protein RAD51. Metastatic breast cancer represents a subtype that has poor
clinical outcome and RAD51 contributes to this. We have determined that reducing RAD51 levels in
aggressive breast cancers results in reduced metastatic growth and sensitivity to chemotherapy. RAD51
supports metastasis via a role in stabilizing cancer genomes however RAD51 also augments metastatic
potential through other mechanisms. These include changes in actin dynamics and changes in gene
metastatic expression profiles via mechanisms that have yet to be fully elucidated. We believe that other
DNA repair proteins could also harbour these roles. Outcomes from these analyses will provide new
potential clinical targets in treating metastatic breast cancer.
Individual research projects for developing new therapeutic targets will have a focus around one of the
following models;
Actin dynamics and metastasis: We find that DNA repair proteins affect actin dynamics, cell morphology
and thus the migration and invasion properties of cancer cells. This determines the metastatic potential of
the cancer and could be targeted to inhibit metastatic spread of cancer.
Transcriptional regulation of metastasis: DNA repair proteins also change the profile of pro-metastatic gene
expression via unknown mechanisms. The ability of DNA repair proteins to bind DNA and simultaneously
bind transcription factors, mean they have the capability to direct gene expression. This is a new function
for this class of proteins.
Animal models of metastasis: We are developing new models of metastasis to test new anti-metastatic
drugs developed in the lab. We are looking to mimic human diseases, with spontaneous metastasis of
breast cancer to specific organs.
70
SCMB Biotechnology Research Projects 2016 | Individual Contributors
DR STEFANO FREGUIA
Centre for Microbial Electrosynthesis
Advanced Water Management Centre
Phone: 07 3346 3221
Email: [email protected]
My research is at the interface between microbial biotechnology and
electrochemistry, an area known as microbial electrochemistry, which has seen a research boom in the last
decade. Electrochemically active bacteria are ubiquitous in nature and are capable of direct and mediated
electron transfer to extracellular insoluble electron acceptors, including mineral oxides and positively
polarised electrodes. Some of these bacteria are also capable of electron transfer in the opposite direction,
i.e. from insoluble electron donors (e.g. metals, elemental sulfur and negatively polarised electrodes) to
soluble electron acceptors. These bacteria can be exploited for a number of biotechnological processes,
including wastewater treatment with simultaneous electricity production (microbial fuel cells), reductive
removal of water pollutants using electricity instead of chemicals, and the concentration of valuable
products from wastewater through the use of ion-selective membranes. In particular, these systems can be
used to recover precious nutrients from wastewaters. Currently, these nutrients are either discharged in
dilute form into the environment or destroyed in energy-intensive wastewater treatment processes. Their
recovery and reuse is an important step towards sustainable resource management. We have currently
two projects in this area that are suitable for honour or master thesis students.
Project 1: Nutrient recovery from source-separated urine using a microbial fuel cell. Urine is an ideal
substrate for a microbial fuel cell, as a consequence of its high organic content, high salinity and high
buffering capacity. Preliminary results have already shown that the organic compounds present in urine can
be effectively oxidised to carbon dioxide at a microbial anode, with concomitant electricity generation. In
this project, the aim is to prove the concept of a three-compartment microbial fuel cell to simultaneously
achieve (i) complete treatment of urine and (ii) recovery of valuable nutrients (primarily nitrogen,
phosphorus and potassium) in the form of a salt.
Project 2: Development of a high-rate microbial biocathode for oxygen reduction. For any microbial fuel cell
to succeed, a strong cathodic process needs be in place to consume the electrons liberated at the anode.
Oxygen is the most suitable electron acceptor in light of its wide availability and high redox potential. The
aim of this project is to establish and fully characterise a microbially catalysed oxygen reduction process at
a cathode. A number of electrode materials will be tested with mixed microbial cultures supplied only with
air and minimal nutrients.
71
SCMB Biotechnology Research Projects 2016 | Individual Contributors
PROFESSOR RICHARD LEWIS
Group Leader, Chemistry and Structural Biology Division
Director, Centre for Pain Research
Phone: 07 3346 2984
Email: [email protected]
Analysis on cone snail venoms using integrated proteomics and transcriptomics to understand the diversity
of cone snail venom peptides and how they contribute to the evolution of distinct predatory and defensive
venoms.
Identification and characterisation of venom peptides acting at ion channels, GPCRs or transporters with
potential to selectively inhibit or activate pain pathways.
72
SCMB Biotechnology Research Projects 2016 | Individual Contributors
DR ZYTA ZIORA
Senior Research Officer
Institute for Molecular Bioscience
Phone: 07 3346 2067
Email: [email protected]
Workshops and other interests:
• Writing literature reviews
• ITC (isothermal titration microcalorimetry)
• Drug design, mode of action, peptide and peptidomimetics chemistry
• Thermodynamics of binding between ligands/metal ions and antibiotics
General research outline
• Improving antibiotic potency by complexing with metal ions.
• Skin treatment for bacterial infection/burns/injury/inflammation/cancer prevention.
Current research projects
1. Enhancement of beta lactams activity through complexation with metal ions.
2. NMR and ITC study of antibiotic complexes with metal ions.
3. Wine tannins, physico-chemical characterization and bio-activity.
4. Bacterial sortase: application to improve antibacterial potency.
My current research projects involve collaboration with:
• Project 1 – University of Heidelberg, Germany/UQCCR, UQ.
• Project 2 – CAI/IMB.
• Project 3 – AWRI, Adelaide/QAAFI.
• Project 4 – IMB/ Pharmacy Australia Centre of Excellence.
Selected Recent Publications:
Zhou Hang, Matthew A. Cooper, Zyta M. Ziora, Platinum-based anticancer drugs encapsulated liposome and
polymeric micelle formulation in clinical trials, Biochemical Compounds, 2016, 4, 1-10.
McRae, J. M.; Ziora Z. M.; Kassara, S.; Cooper, M.A.; Smith, P. A. Ethanol concentration influences the
mechanisms of wine tannin interactions with poly(L-proline) in model wine, J. AgricultureFood Chem., 2015,
63, 4345−4352.
Cheng, M.; Ziora, Z. M.; Hansford K.; Blaskovich, M. A.; Butler, M. S.; Cooper, M. A. Anti-cooperative ligand
binding and dimerisation in the glycopeptide antibiotic dalbavancin, Org. Biomol. Chem., Org. Biomol. Chem.,
2014, 12, 2568.
Ziora, Z. M.; Blaskovich, M. A.; Toth, I.; Cooper, M. A. Lipoamino acids as major components of absorption
promoters in drug delivery, Curr. Top. Med. Chem. 2012, 12, 1562-1580.
Ziora, Z. M.; Wimmer, N.; New, R.; Skwarczynski, M.; Toth, I. Lipopeptides for the Fragment-based
Pharmaceutics Design, Int. J. Org. Chem. 2012, 2, 75-81. (cover story)
Ziora, Z.; Skwarczynski, M.; Kiso, Y. Medicinal chemistry of a-hydroxy-b-amino acids. In Andrew B. Hughes
(Ed.), Amino Acids, Peptides and Proteins in Organic Chemistry: Volume 4 - Protection Reactions, Medicinal
Chemistry, Combinatorial Synthesis Weinheim, Germany: Wiley. 2011, pp. 189-234.
73
SCMB Biotechnology Research Projects 2016 | Individual Contributors
Queensland
Alliance for
Agriculture and
Food
Innovation
74
SCMB Biotechnology Research Projects 2016 | Individual Contributors
DR FEMI AKINSANMI
Queensland Alliance for Agriculture and Food Innovation
Ecosciences Precinct, Boggo Road, Dutton Park
Phone: 07 3255 4338
Email: [email protected]
ASSOCIATE PROFESSOR
ANDRE DRENTH
Queensland Alliance for Agriculture and Food Innovation
Ecosciences Precinct, Boggo Road, Dutton Park
Phone: 07 3255 4338
Email: [email protected]
Phylogenetic analysis of Pseudocercospora macadamiae
Our previous study with PCR-RFLP has identified six genotypes in P. macadamiae populations from three
geographical areas in Australia. This study will evaluate the phylogenetic relationship between isolates of P.
macadamiae obtained from different cultivars in all the macadamia producing regions of Australia. Selected
genes will be used to study sequence divergence among the P. macadamiae isolates and Pseudocercospora
species. Sequence analysis will help to detect more fine scale genotypic diversity among P. macadamiae
and enable a direct comparison of the species causing husk spot in macadamia and leaf spots in other hosts
in Australia.
75
SCMB Biotechnology Research Projects 2016 | Individual Contributors
DR FEMI AKINSANMI
Queensland Alliance for Agriculture and Food Innovation
Ecosciences Precinct, Boggo Road, Dutton Park
Phone: 07 3255 4338
Email: [email protected]
Microbial composition of macadamia husk
Macadamia husks are lignocellulosic materials therefore, microorganisms including fungi as well as
actinomycetes and other bacteria are able to colonise the tissue. Some of these microbes are important in
bio-decomposition of the materials or other essential biological functions. This study will elucidate the
microbial community dynamics on macadamia husks in relation to seasonality, fruit age and positional
canopy height of the tree.
AVAILABLE FROM 2016 SEM 2 AND 2017 SEM 1
Characterisation and diagnostics of blossom blight in macadamia
Raceme blight also known as blossom or flower blight and grey mould are used to describe various diseases
and disorders of macadamia flowers. Different fungi and oomycetes have been reported as causal agents of
blossom blight in macadamia. In spite of distinct and remarkable differences in the pathogens, there is still
lack of adequate knowledge of the symptom development and disease epidemiology for each pathogenhost interaction. This study will examine the etiology of the disease and establish the epidemiological
conditions necessary for infection. The scholar will use plant pathology research techniques and gain
advanced plant science and molecular skills. It is expected that the scholar will contribute to publications
from the research. Useful references: Phytopathology (1972) 62: 316-319; (1976) 66: 546-548
Development of LAMP assay to detect husk spot
Husk spot is a unique disease of macadamia in Australia. The disease leads to premature abscission of
macadamia nut. Existing conventional or traditional diagnostic method for husk spot is laborious and takes
4-6 weeks. Lack of diagnostic tool for early detection of infection before symptom expression hinders
studies on infection process. Therefore, the aim of this study is to improve the detection and quantification
of husk spot infection. The study will develop a simple and rapid diagnostic tool using the loop mediated
isothermal amplification (LAMP) assay for early detection and characterisation of macadamia cultivars. The
scholar will use existing DNA sequence data for husk spot fungus isolates to develop the LAMP assay.
Scholars will gain advanced plant science and molecular skills and contribute to publications from the
research. Useful references: Australasian Plant Pathology (2009) 38: 36-43; International Journal of Food
Microbiology (2010) 140 183-191.
How many Botryosphaeriaceae fungi are there in macadamia?
Botryosphaeriacae fungi are of significant economic importance. They are major pathogens in several plant
hosts in temperate, tropical and subtropical crops including macadamia, an Australian native plant. Many
names based on morphological and host association are used to distinguish the species complex. However,
these are mostly inaccurate. This project proposes to identify and classify the isolates, and based on
molecular phylogenetic evidence, reveal distinct and new taxa in this species complex. This project will
identify species within the family Botryosphariaecae that are associated with macadamia. The overall aim
of the study is to determine if species of the Botryosphariaecae are able to inhabit macadamia tissues as
‘non-pathogenic’ fungi. The scholar will use general plant pathology research techniques including
molecular tools to test the research hypotheses. Scholars will gain advanced plant science and molecular
skills and contribute to publications from the research. Useful references: Australasian Plant Pathology
(2009) 38: 36-43; International Journal of Food Microbiology (2010) 140 183-191.
76
SCMB Biotechnology Research Projects 2016 | Individual Contributors
DR FEMI AKINSANMI
Queensland Alliance for Agriculture and Food Innovation
Ecosciences Precinct, Boggo Road, Dutton Park
Phone: 07 3255 4338
Email: [email protected]
DR BRUCE TOPP
Queensland Alliance for Agriculture and Food Innovation
Ecosciences Precinct, Boggo Road, Dutton Park
Phone: 07 5453-5973
Email: [email protected]
Response of species and cultivars of Macadamia to Phytophthora cinnamomi
Our previous study suggests that macadamia is tolerant to Phytophthora cinnamomi, however, in certain
conditions the soilborne pathogen is able to cause significant damage to macadamia. This study will
evaluate the resistance/susceptibility of Macadamia species and commercial cultivars to root rot and stem
canker caused by P. cinnamomi.
77
SCMB Biotechnology Research Projects 2016 | Individual Contributors
DR KARINE CHENU
Queensland Alliance for Agriculture and Food Innovation
(Toowoomba – Gatton)
Phone: 07 4688 1357
Email: [email protected]
Understanding the basis of transpiration efficiency in wheat
Wheat productivity is limited by the amount of biomass that plants can produce for the limited water
supply they can access. Existing conditions in Australia and future predictions for increased temperature,
evaporative demand and water scarcity enhance the need for higher transpiration-efficiency crops (“more
crop per drop”). To breed for new wheat varieties with increased transpiration efficiency, the physiological
responses of transpiration rate to environment need to be better understood. This work will use the new
state-of-the-art UQ-Gatton lysimeter facility to investigate whole-plant and leaf-level transpiration rate and
efficiency of contrasting wheat genotypes, and to characterise their response to evaporative demand and
soil water status.
78
SCMB Biotechnology Research Projects 2016 | Individual Contributors
ASSOCIATE PROFESSOR
RALF DIETZGEN
CILR, John Hines Building and QAAFI, Ritchie Bldg,
UQ St Lucia Campus
Phone: 07 3346 6503
Email: [email protected]
DR PAUL SCOTT
CILR, John Hines Building and QAAFI, Ritchie Bldg,
UQ St Lucia Campus
Phone: 07 3346 6206
Email: [email protected]
PROFESSOR PETER GRESSHOFF
CILR, John Hines Building and QAAFI, Ritchie Bldg,
UQ St Lucia Campus
Phone: 07 3365 3550
Email: [email protected]
Identification & characterization of viruses that infect the biofuel tree Pongamia pinnata
Plant functional genomics research can benefit greatly from high throughput silencing of genes to
determine their function(s) during development and defense against abiotic and biotic stress. Replicating
viruses are efficient inducers of RNA silencing in plants and have been used extensively to silence plant
genes in Arabidopsis, legumes, cereals and some horticultural crops. This project aims to identify and
characterize viruses that infect P. pinnata trees to subsequently construct suitable viruses into virusinduced gene silencing (VIGS) vectors to allow functional genomic studies. Symptomatic and asymptomatic
leaves will be collected from diverse locations and samples analysed by dsRNA extraction and gel
electrophoresis analysis and by next generation high-throughput sequencing of total RNA.
79
SCMB Biotechnology Research Projects 2016 | Individual Contributors
ASSOCIATE PROFESSOR
RALF DIETZGEN
Queensland Alliance for Agriculture and Food Innovation
Ritchie Laboratories, St. Lucia Campus
Phone: 07 3346 6503 / Email: [email protected]
Website: http://www.qaafi.uq.edu.au//?page=157981
Molecular Plant-Microbe Interactions
My research interest is in the discovery and biodiversity of genes, proteins and regulatory RNAs in plants and
viruses and their interactions in agricultural systems. Increased knowledge of these molecular interactions will
enable improved crop performance and better disease control. Special interests include the characterization of
plant-adapted rhabdoviruses and tospoviruses, virus diagnosis and molecular evolution, taxonomy of negativesense RNA viruses, RNA silencing pathways for pest and disease resistance, and functional genomics and
molecular markers in tropical horticulture.
Project 1: Characterization and control of a new rhabdovirus from lucerne.
Rhabdoviruses are important pathogens of humans, animals and plants. Plant-adapted rhabdoviruses multiply in
both their plant hosts and arthropod vectors. We aim to understand the molecular interactions in both hosts to
devise better means of virus control. In this project you will participate in the analysis of the genome and
genetic diversity of a new, economically important rhabdovirus from lucerne. The research includes
development of a diagnostic assay to identify the natural host range and potential arthropod vectors. Virus-host
protein interactions and cell-to-cell transport will be studied to gain insights into the virus’ replication and
movement processes. In collaboration with colleagues in Argentina, we will also develop gene constructs for
RNA silencing-mediated resistance and search for natural resistance genes in available germplasm.
Project 2: Identification & characterization of viruses that infect the biofuel tree Pongamia pinnata.
Plant functional genomics research can benefit greatly from high throughput silencing of genes to determine
their function(s) during development and defense against abiotic and biotic stress. Replicating viruses are
efficient inducers of RNA silencing in plants and have been used extensively to silence plant genes in
Arabidopsis, legumes, cereals and some horticultural crops. This project aims to identify and characterize viruses
that infect P. pinnata trees to subsequently construct suitable viruses into virus-induced gene silencing (VIGS)
vectors to allow functional genomic studies. Symptomatic and asymptomatic leaves will be collected from
diverse locations and samples analysed by dsRNA extraction and gel electrophoresis analysis and by next
generation high-throughput sequencing of total RNA. This is a collaborative project with Professor Peter
Gresshoff ([email protected]) & Dr. Paul Scott, Centre for Integrative Legume Research, School of
Agriculture and Food Science.
References:
Dietzgen, R.G., Kuzmin, I.V. (eds.) (2012) Rhabdoviruses: Molecular taxonomy, evolution, genomics, ecology,
host-vector interactions, cytopathology and control. Caister Acad. Press, Norfolk, UK, 276 pp, ISBN 978-1908230-11-9
Martin, K.M., Dietzgen, R.G., Wang, R.Y., Goodin, M.M. (2012) Lettuce necrotic yellows cytorhabdovirus protein
localization and interaction map and comparison with nucleorhabdoviruses. Journal of General Virology 93: 906914.
Dietzgen, R.G., Martin, K.M., Anderson, G., Goodin M.M. (2012) In planta localization and interactions of
impatiens necrotic spot tospovirus proteins. Journal of General Virology 93: 2490-2495.
Klein-Marcuschamer, D., Turner, C., Allen, M., Dietzgen, R.G., Peter Gray, Gresshoff, P.M., Hankamer, B.,
Heimann, K., Scott, P., Speight, R., Stephens, E., and Nielsen, L.K. (2013) Technoeconomic analysis of renewable
aviation fuel from microalgae, Pongamia pinnata, and sugarcane. Biofuels, Bioproducts & Biorefining: doi:
10.1002/bbb.1404.
Biswas, B., Kazakoff, S.H., Jiang, Q., Samuel, S., Gresshoff, P.M., and Scott, P.T. (2013) Genetic and genomic
analysis of the tree legume Pongamia pinnata as a feedstock for biofuel. Genome Biology (in press).
80
SCMB Biotechnology Research Projects 2016 | Individual Contributors
DR ANDREW GEERING
Queensland Alliance for Agriculture and Food Innovation
Ecosciences Precinct, Boggo Road, Dutton Park
Phone: 07 32554389
Email: [email protected]
ASSOCIATE PROFESSOR
JOHN THOMAS
Phone: 07 3255 4393
Email: [email protected]
Towards a better understanding of how plant pararetroviruses process proteins
Banana streak virus (BSV) is a representative of the only group of pararetroviruses in plants. BSV is distantly
related to Human immunodeficiency virus (HIV) although it is only infects plants. BSV has a simple
replication strategy, producing the majority of the proteins it needs on one large polyprotein, which is then
cleaved into functional units through the action of a virus-encoded aspartic protease. Retroviral aspartic
proteases (APs) are unusual in that it is impossible to predict their substrate preferences through sequence
analysis alone and cleavage sites must be predicted empirically. Recently, in our laboratory, we have
determined the boundaries of the BSV capsid protein and using this information, made some predictions as
to where the AP is cleaving. The next step in this line of research, which is the topic of this project, is to
express the BSV AP in vitro and demonstrate cleavage using synthetic peptides as substrates.
81
SCMB Biotechnology Research Projects 2016 | Individual Contributors
DR JIM HANAN
Biological Information Technology Group
Queensland Alliance for Agriculture and Food Innovation
Phone: 07 3365 8234
Email: [email protected]
Towards better fruit and nut yields: Understanding tree architecture
This project will take a computational modeling approach to understanding the dynamics of tree
architecture in a selected tropical or sub-tropical fruit or nut tree species. After reviewing what is known
about the flushing and flowering of the selected species, data on tree architecture will be collected, and a
virtual plant model will be developed. Functional aspects of interest may also be incorporated.
82
SCMB Biotechnology Research Projects 2016 | Individual Contributors
ASSOCIATE PROFESSOR
ELIZABETH AITKEN
School of Agriculture and Food Sciences
St Lucia campus, The University of Queensland
Phone: (07) 3365 4775
Email: [email protected]
DR LEE HICKEY
Queensland Alliance for Agriculture and Food Innovation
Phone: (07) 3365 4805
Email: [email protected]
Simultaneous selection for resistance to crown rot and foliar diseases in barley
Crown rot, caused by the pathogen Fusarium pseudograminearum, is an important disease of winter
cereals such as wheat and barley. This project aims to develop a high-throughput phenotypic screening
assay that enables simultaneous selection for resistance to crown rot and foliar diseases (e.g. leaf rust
caused by Puccinia hordei Otth., and spot form of net blotch caused by Pyrenophora teres f. maculate) in
segregating populations of barley grown under controlled environmental conditions. The screening assay
will incorporate rapid generation advance techniques for the purpose of accelerating breeding cycles.
Outputs of the Honours research project will be: 1) new screening methodology, 2) improved knowledge of
the genetic control of resistance to crown rot in barley, and 3) germplasm enriched for the target traits,
which will be a useful resource for further breeding efforts in Australia. The student will gain hands-on
experience in pathology, plant breeding and genetics.
83
SCMB Biotechnology Research Projects 2016 | Individual Contributors
ASSOCIATE PROFESSOR ATHOL KLIEVE
BAgSc MRurSc PhD MASM
UQ Gatton campus or Eco Science Precinct, Dutton Park
Phone: 07 5460 1255 or 3255 4269 (Gatton)
Email: [email protected]
DR JUSTIN GIBSON
BVSc PhD
Phone: 07 5460 1830
Email: [email protected]
Naturally occurring bacteriocins; a novel therapy for the treatment of multidrug-resistant E.coli urinary
tract infections in dogs
This is a small project, with operating funds suitable for an honours project. It would suit a student who is
interested in novel, non-antimicrobial treatments of bacterial infections. The overall aim of this research is
to detect, isolate and use naturally occurring bacteriocins to reduce or eliminate Multiple Drug Resistant
(MDR) Escherichia coli in the urinary tract of dogs, as an alternative to the use of antibiotics for the
treatment and management of recurrent MDR cystitis. The Honours project will be the first step in this
process and involves the isolation and characterisation of bacteria that produce bacteriocins. Techniques
that will be gained through the project will be both traditional microbiology and molecular biology based.
84
SCMB Biotechnology Research Projects 2016 | Individual Contributors
DR MARY FLETCHER
Health and Food Sciences Precinct, Coopers Plains
Phone: 07 3276 6089
Email: [email protected]
Project 1: The prevalence of indospicine in Indigofera plant species by LC-MS/MS
The amino acid indospicine is an arginine-analogue found only in Indigofera plant species and has been
shown experimentally to be hepatotoxic in a number of animal species. Indospicine is an unusual amino
acid in that it is not incorporated into proteins, but is present as the free amino acid. Indospicine
accumulates as the free amino acid in tissues of animals fed Indigofera plant material, and such residues
have been shown to persist for several months after cessation of feeding. Dogs are particularly sensitive to
the hepatotoxic affects of indospicine, and canine fatalities have been reported from the consumption of
indospicine contaminated meat from both camels and horses grazing Indigofera plants in central Australia.
Indigofera plant species are generally quite palatable with good nutritive value, and have been proposed as
potentially valuable forage species. However, the presence of indospicine has limited this potential with
high intake of Indigofera shown to have hepatotoxic effects in grazing animals including cattle. This is a
laboratory-based project investigating the prevalence of indospicine in a range of Indigofera plant species,
and will involve the extraction and chemical analysis of plant samples by liquid chromatography-tandem
mass spectrometry (LC-MS/MS).
Project 2: Investigating the Cause of Cleft Palate in Spectacled Flying Fox
The spectacled flying fox (Pteropus conspicillatus) is a native species with
limited distribution in north-eastern Queensland and feeds on fruits and
blossom of a wide range of vegetation. The increasing occurrence of cleft
palate in flying fox pups is one factor which threatens the survival of this
“vulnerable” species. This project will investigate the links between the
occurrence of cleft palate and the consumption of fruit of wild tobacco
Solanum mauritianum, a source of the teratogenic steroidal alkaloid
solasodine. The project will collaborate with wildlife scientists and
volunteers who will provide samples of plant material and animal bloods
for analysis by liquid chromatography mass spectrometry (LC-MS) by the student. A background in
chemistry with some knowledge of mass spectrometry is essential for this project, as well as an interest in
applying such skills to address an ecological problem.
This project will be located at the Health and Food Sciences Precinct at Coopers Plains, Brisbane.
(http://www.qld.gov.au/dsitia/science/assets/documents/health-food-sciences-precinct-brochure.pdf ) in
the laboratory of Dr Mary Fletcher (QAAFI-UQ). http://www.qaafi.uq.edu.au/fletcher-dr-mary
85
SCMB Biotechnology Research Projects 2016 | Individual Contributors
DR MANUEL RODRIGUEZ VALLE
BBIOTECH/PhD
Queensland Alliance for Agriculture and Food Innovation (QAAFI)/UQ, St Lucia.
Address: DAFF, Applied Biotechnology Livestock, Level 3, Queensland Biosciences
Precinct, 306 Carmody Rd, UQ, St Lucia, Qld 4072
Phone: 07 3255 4529
Email: [email protected]
DR ALA LEW-TABOR
PhD
Queensland Alliance for Agriculture and Food Innovation (QAAFI)/UQ, St Lucia.
Address: DAFF, Applied Biotechnology Livestock, Level 3, Queensland Biosciences
Precinct, 306 Carmody Rd, UQ, St Lucia, Qld 4072
Phone: 07 3255 4535 / Mobile: 0417 737 595
Email: [email protected]
Harnessing the genome of the Australian paralysis tick to develop effective control products
Ixodes holocyclus (paralysis tick) occurs along the eastern coast of Australia from far north Queensland to
southern Victoria and is the most virulent tick species in terms of paralysis. Each year I. holocyclus affects
~100 000 domestic animals, with up to 10 000 companion animals. Also, humans are affected by tick bites
provoking hypersensitivity reactions. Toxin is produced as the adult female tick engorges and paralysis is
frequently induced just prior to detachment. In this research project a transcriptome analysis of salivary
glands and viscera samples dissected from fully-engorged I. holocyclus ticks was conducted. cDNA was
synthesised from ticks collected from bandicoots or dogs and cats with paralysis symptoms. The cDNA was
analysed by 454 and Illumina technologies. Seventeen transcripts related with toxins were found within the
samples under study. The transcriptome information acquired from the I. holocyclus tick conforms a unique
database for the paralysis tick stored at the Centre for Comparative Genomics, Murdoch University.
Holotoxins1, 2 and 3 were cloned into the Pichia pastoris vector for expression, and purification for animal
screening. Other studies need to be conducted to find other proteins directly related with paralysis tick
symptoms. Therefore, in the framework of an ARC linkage grant, the development and screening of a
display library prepared from I. holocyclus salivary gland cDNA is proposed. The cDNA will be cloned into
the yeast vector pYD1 for the expression of paralysis tick proteins on the surface of Saccharomyces
cereviseae. The recombinant yeast which express proteins associated with the host – parasite interaction
and paralysis tick symptoms will be selected using fluorescence activated cell sorting (FACS). Hyper immune
sera obtained from dogs resistant to paralysis tick will be utilised for sorting the recombinant yeast by
FACS. Selected recombinant transformants will be used for expression, purification and analysis for optimal
expression of the recombinant proteins in liquid cultures. Finally, the recombinant proteins will be tested in
animals to determine their capability to protect against paralysis symptoms. Synaptosome and neuronal
cell receptor assays need to be developed in order to examine the mechanisms of paralysis toxin(s). We are
seeking post-graduate students (Honours, Masters, PhD) to contribute to this exciting research program.
86
SCMB Biotechnology Research Projects 2016 | Individual Contributors
DR MANUEL RODRIGUEZ VALLE
BBIOTECH/PhD
Queensland Alliance for Agriculture and Food Innovation (QAAFI)/UQ, St Lucia.
Address: DAFF, Applied Biotechnology Livestock, Level 3, Queensland Biosciences
Precinct, 306 Carmody Rd, UQ, St Lucia, Qld 4072
Phone: 07 3255 4529
Email: [email protected]
Serine Protease Inhibitors of Rhipicephalus microplus (Cattle tick) expressed in transgenic plants.
Proteases are very important molecules implicated in the protection and survival of different organisms
against pathogenic entities that include virus, insects and other parasites. An overexpression or higher
concentrations of these proteases can lead to potentially damaging of these organisms. Some insects and
many of the phytopathogenic microorganisms secrete extracellular proteases causing proteolytic
degradation of proteins which is directly related with their pathogenesis. However, plants have generated
different defense mechanism to inhibit proteolysis activity in these pathogenic organisms such as secretion
of specific proteases inhibitors. In most plants, natural mechanisms to control insect attack include
protease inhibitor (PI) accumulation [1]. Additions of PIs to insect diets have been shown to limit insect
development [2-4]. The overexpression of PI's in transgenic plants may decrease virus and insect damage.
Researches effort conducted previously have demonstrated that the expression of PIs in plant is an
environmentally sound method of pest control [5, 6].
Aim: The expression in plants of serine protease inhibitor of R. microplus (Cattle tick) can reduce the
pathogenic effect of virus and insects in these transgenic plants.
References
1.
Ryan CA: Proteolytic enzymes and their inhibitors in plants. Ann Rev Plant Physiol 1973, 24:173 186.
2.
Gatehouse AMR, Gatehouse, J.A., Boulter, D.: Isolation and characterization of trypsin inhibitors
from cowpea. Phytochemistry 1980, 19:751-756.
3.
Hilder VA, Gatehouse, A.M.R., Sheerman, S.E., Barker, R.F., Boulter, D.: A novel mechanism of
insect resistance engineered into tobacco. 1987, 330:160-163.
4.
Johnson R, Narva6z, J., An, G., Ryan, C.A. : Expression of proteinase inhibitors I and II in transgenic
tobacco plants: effects on natural defense against Manduca sexta larvae. Proc Nat Acad Sciences
1989, 86:9871-9875.
5.
Thomas JC, Adams DG, Keppenne VD, Wasmann CC, Brown JK, Kanost MR, Bohnert HJ: Protease
inhibitors of Manduca sexta expressed in transgenic cotton. Plant cell reports 1995, 14(12):758762.
6.
Alvarez-Alfageme F, Maharramov J, Carrillo L, Vandenabeele S, Vercammen D, Van Breusegem F,
Smagghe G: Potential use of a serpin from Arabidopsis for pest control. PLoS ONE 2011,
6(5):e20278.
87
SCMB Biotechnology Research Projects 2016 | Individual Contributors
DR SUSHIL DHITAL
Centre for Nutrition and Food Sciences (CNAFS)
Queensland Alliance for Agriculture and Food Innovation (QAAFI)
ARC Centre of Excellence in Plant Cell Walls
Room S426, Hartley Teakle Building, The University of Queensland
Phone: 07 334 67373
Email: [email protected]
Bakery products such as biscuits, cakes and breads are widely consumed processed foods in western
society. The major ingredients in bakery products are wheat flour, the other ingredients being fat, sugar
etc. On consumption of bakery products, the starch in wheat flour is rapidly digested increasing the
postprandial blood glucose level, which might have a negative health effect and is often associated with
type II diabetes. This project aims to formulate low fat and low sugar bakery products incorporated with
enzyme resistant starch (ERS) and investigate the textural attributes of the baked products as well as
change in morphological and micro structure of starches in bakery products.
88