Discovery through
Innovation
Manchester Institute of Biotechnology
Discovery through Innovation
Research at the Manchester Institute of Biotechnology
Contents
43
Innovation in Action
45
Research Centres, Institutes and Facilities
48
Postgraduate and Training
51
Science and Society
53
12
18
22
Grand Challenge:
Biomedical and Healthcare
Grand Challenge:
Industrial Biotechnology
Grand Challenge:
Biofuels and Energy
Faculty Honours
57
Selected Publications
Office of the Director
Nigel Scrutton
Director
Lesley-Ann Miller Communications Manager
Rosalind Le Feuvre Research and Planning Manager
Penny Johnson Research Strategy Co-ordinator (EU and Industry)
Janet England Support Services Manager
Editor
Lesley-Ann Miller
Design & Production
WeAreCreation.co.uk
www.mib.manchester.ac.uk
[email protected]
26
31
Spotlight:
Centre for Synthetic Biology
Spotlight:
Systems Biology
34
Spotlight:
Text Mining
37
Spotlight:
Technologies
3
Manchester Institute
of Biotechnology
Driving discovery through innovation
Fig. 1.0
Discovery through
The Manchester Institute of Biotechnology
inform and are informed by our research
Grand Challenges and showcasing a
(MIB) is one of the leading biotechnology
at the molecular, systems and design levels
selected portfolio of projects that illustrate
research institutes in the world. Focusing on
as illustrated in our Discovery through
the diversity, quality and dynamism of
advanced quantitative approaches to specific
Innovation Pipeline (fig 1.0).
our research teams. Our reputation as an
biotechnology challenges at the interface,
the MIB enjoys a unique pluralistic and open
research culture that is realised through a
coherent and integrated research concept
and the establishment of a unique multi- and
inter-disciplinary community of researchers
committed to working across discipline
boundaries.
The MIB is based at the John Garside
Building and houses over 500 research staff
and students from 52 research groups from
across The University of Manchester from
the Faculties of Engineering and Physical
Sciences, Life Sciences, and Medical and
Human Sciences. With a strong emphasis on
translational research, knowledge transfer
and discovery through innovation our
philosophy has placed us in a strong position
to address a series of Grand Challenges that
4
We pursue and are actively engaged in
challenging research projects that enable
us to make significant advances in science
and engineering to benefit industry
and society. Our track record in driving
major interdisciplinary programmes in
Innovation Pipeline
international leader in the biotechnology
field is evidenced with over 1400
publications, since 2009, in major journals
and the impact of the Institute’s research is
evident from a sustained commitment to the
Harnessing the synergy of interdisciplinarity
Focusing on specific challenges in biotechnology the co localisation of researchers from distinct
disciplines generates interdisciplinary teams with unique capabilities.
successful translation of basic science into
commercial success.
Design promotes interaction
£90M in external funding since MIB’s
As a leading industry-interfaced
Reflecting the needs of interdisciplinary science, the MIB features open-plan, multifunctional
The Manchester Institute of
inception in 2006 and our portfolio
biotechnology institute we are proud to
laboratories and extensive specialist research facilities.
Biotechnology is committed to
continues to grow substantially primarily
engage in technology transfers and have
through a ‘tightening’ of our focus in areas
a number of strategic partnerships with
of core strength (industrial biotechnology;
companies from the chemical, biotechnology
synthetic biology; catalysis science; systems-
and biopharmaceutical sectors to translate
based research; biomedical biotechnology;
research council funding into products and
fuels and energy research), and supported
services for the betterment of all people and
by strategic recruitment to new leadership
the environment across the globe.
Innovation in action
Nigel Scrutton
Advancing economic and societal development through knowledge generation and transfer.
health, the energy economy, food
Director
Enabling companies of all sizes to benefit from our research technology and expertise.
security, industrial transformations and
Exploiting commercially significant innovation through licensing and the creation of spin-out/spin-ins.
the environment.
biotechnology has attracted more than
positions in the Institute.
Our research strengths are showcased in
the ensuing pages defining our research
the pursuit of research excellence,
education, knowledge transfer
Discovery through innovation
and discovery through innovation
Delivering internationally recognised programmes across all disciplines, with a strong emphasis
whereby a coherent and integrated
on translational research, knowledge transfer and discovery through innovation.
interdisciplinary research community
work towards developing new
biotechnologies that will find
applications in areas such as human
5
The University of Manchester
Our goal, outlined in the Manchester 2020
quality of our research activity is unrivalled
pioneering approaches to major global
strategic plan, is to establish the University as
in the UK. We have a distinguished history
challenges in biotechnology it has evolved
a major centre for interdisciplinary research.
in research, innovation and enterprise
into one of the leading biotechnology
The large scale and quality of our activity at
stretching back over 180 years with many of
research institutes in the world.
Manchester sets us apart. We are able to
the major advances of the twentieth century
combine disciplines and capabilities to meet
having been discovered at the University.
both the challenges of leading-edge research
of all people, through knowledge transfer
Our institutes carry responsibility for several
and education and this commitment is
of the University’s key research priorities,
firmly embedded in the global challenges
working in areas where we have achieved
that constitute the unique research vision
The University of Manchester is one of
or aspire to world-leading status. The
of the MIB whose role is integral to the
the world’s leading centres for biomedical
Manchester Institute of Biotechnology was
advancement of the research mission of the
and biotechnology research that sits at the
the first university-based, purpose-built
University.
forefront of new discoveries in science and
interdisciplinary research institute of its kind
engineering. Research is at the heart of the
in the UK. Through the establishment of
University and the sheer scale, diversity and
multi-skilled interdisciplinary teams applying
Expanding cross campus
collaboration
in spectroscopy through Professor Peter
In a programme funded by the EPSRC the MIB
Gardner. Our systems/modelling/text mining
engaged in a suite of short-term speculative
activities continue to assemble cross-faculty
activities to consolidate the cross-disciplinary
teams of researchers to deliver innovative
culture within the Institute. In one project,
research at the forefront of medical
Professor Peter Gardner in collaboration with
biotechnology.
Professor Mark Dunne (FLS) differentiated four
and the external demands of society,
business and other stakeholders.
We continue to develop collaborations across
the University campus with current research
grant funding aligned with 83 research
Professor Luke Georghiou
Vice President for Research
on the design of these filter stages, and
numbers obtained and the addition of
use cutting edge science and technology
labelling reagents mean that these methods
to generate a completely new approach to
There has been a recent explosion in interest
are not suitable for widespread application of
stem cell purification. Specialist techniques
in and potential applications of stem cells.
stem cell therapy. Stem cells have yet to find
such as microfluidics, nanotechnology, rapid
Their potential for therapeutic medical
global application, because of their rarity. This
microstructure prototyping will be combined
applications is particularly exciting, with
project proposes to change the current stem
with the latest ideas in cell biochemistry
Following on from earlier work led by
the real prospect of growing replacement
cell sorting methods from low throughput
and cell biorecognition to fulfil the primary
Professor John Vickerman which utilised
tissue and bone to overcome a wide variety
one-by-one techniques to very high
objective of making it easier, cheaper and
separate cell lines in pancreatic stem cells using
funding successes and applications endorse
FTIR cell population imaging technologies.
Cross-disciplinary feasibility
Manchester Institutes: Photon Science
Stem cell fractionation using
interactions with artificial matrices
of modern cell sorters the relatively small
groups from all four Faculties. Recent
a closer alliance with other University of
6
We are committed to enhancing the lives
Institute, Manchester Institute of Innovation
There are numerous areas of research within
Research, and the Institute for Science,
the biological and biomedical field that
imaging Mass Spectrometry for 2D and 3D
of disease conditions. Stem cells also have
throughput alternatives that will be capable
faster to harvest useful stem cells. The benefit
Ethics and Innovation. The development of
require the ability to quantitatively analyse
cellular characterisation in an Alzheimer’s
an important role in diagnostics, and have
of sorting millions of cells simultaneously.
to society will be huge, making the possibility
our synthetic biology (SynBio) activity has
single cells and large cell populations.
study, Professor Roy Goodacre and Professor
already shown promise in drug discovery
The key to this will be the design of a series
of stem cell therapy a reality for everyone.
of filters that behave as smart sieves. The
developed closer alliances with members of
For example, metabolomic studies have
Nick Lockyer will join a collaborative team
research. To date, the key limitation to
the Faculty of Humanities and broader, more
the potential to yield understanding of
of researchers from FLS led by Professor
the exploitation of stem cells has been
stem cells will be poured through new filters
comprehensive, links with the Faculty of
complex disease processes, drug toxicity and
Alan Dickson that will seek to describe and
their scarcity. Furthermore, even when it is
that will recognise the cells by their shape,
Engineering and Physical Sciences and with
cellular function whilst the development of
understand the heterogeneity of stem cell
possible to source stem cells, there is still the
size, flexibility and their chemical signature,
the Faculty of Life Sciences. Our interactions
innovative tools for accurate measurement
populations at the molecular level. A stem
formidable task of purification and sorting
without the addition of any extra reagents.
with the Faculty of Medicine and Human
of transcripts and proteins necessitates novel
cell model has been selected that has major
of the usable cells from cells that have
A set of filters will be assembled; one on
Sciences have developed significantly
sample handling, analyte amplification and
significance in finding a potential cure for
differentiated into unusable types. Presently,
top of the other, to allow rapid screening of
through the appointment of Professor
use of miniaturisation and microfluidics to
diabetes, but which also serves as a model
stem cells are labelled with markers and
a mixture that contains both the valuable
Clare Mills, but also in the metabolomics
assist with high throughput measurements to
for the general progression of stem cells
then sorted one-by-one using very expensive
wanted stem cells, alongside less useful
area through Professor Roy Goodacre and
achieve sensitive detection.
towards a specific functional fate.
instruments. Despite the very high speed
cells. This research programme will focus
This is an EPSRC funded project involving
partners from across the University:
Professor Nick Goddard in collaboration
with Professors Cathy Merry (Materials),
Cay Kielty (FLS), Tony Day (FLS), Chris Ward
(Dentistry) from The University of Manchester
and Professors Steve Eichhorn from the
University of Exeter and Peter Fielden from
Lancaster University.
7
and carbon dioxide to engine-ready
and activity of open-source software. The
determinants of common and rare
fuels. In a separately funded project,
Linked2Safety project (Advancing clinical
skeletal diseases to gain a mechanistic
a computational perspective is being
practice and data security in clinical
understanding of disease processes and
undertaken by Professor Paul Popelier who
research) brings together 11 partners to
age-related changes.
is developing innovative QSPR models and
develop a secure framework to facilitate
expert systems for predicting toxicity of
the efficient and homogenized access
ionic liquids in the provision of safe green
to shared distributed Electronical Health
solvents for the future.
Records (EHRs) which would impact
The Manchester Centre for Integrative
Engaging with Europe
and beyond
Beyond The University of Manchester we
with the aim of developing sustainable
and industrial researchers looking to
have a strong portfolio of national and
biological and chemical alternatives to
develop enzymatic methods for green
international collaborations and networks
finite materials, such as precious metals,
oxidation chemistry through the isolation,
with academics and industry. The diversity
which are currently used as catalysts in
redesign and application of cytochrome
and quality of our research programmes is
the manufacture of medicines. CHEM21
P450 enzymes that can be recruited
reflected in publications in major journals,
will run initially for four years with
for the clean, green chemical synthesis
with over 500 publications with over 280
funding from the Innovative Medicines
of important intermediates in the bulk
research institutes from over 65 countries.
Initiative. BIONEXGEN (Developing
chemical, pharmaceutical and agrochemical
The impact of the Institute’s research is
the next generation of biocatalysts for
industries.
evident from a sustained commitment to
industrial chemical synthesis) is another
the successful translation of fundamental
flagship EU collaborative research project
science into commercial success.
developing next generation biocatalysts
Our EU portfolio continues to grow, with
current live awards in the region of £14 million, through collaborative research
programmes and major EU training
networks.
in the chemical industry. This consortium
consists of 17 institutions from university
research groups, small and medium sized
companies, to BASF, the world’s leading
chemical company. Professor Nicholas
Systems Biology (MCISB) is involved
The diversity of our research in the
Framework Programme, iFAAM (Integrated
in SYNPOL (Biopolymers from syngas
biomedical and healthcare arena received
Approaches to Food Allergen and
fermentation) working alongside 13
an EU funding boost with GlycoBioM
Allergy Risk Management), will develop
partners across Europe. This project
(Tools for the detecton of novel glycol-
evidence-based approaches and tools for
aims to develop a platform integrating
biomarkers) bringing together Europe’s
the management of allergens in food.
biopolymer production through modern
leading scientists to study glycosylation.
The Manchester team will work with 38
processing technologies, with bacterial
Hailing from Croatia (Genos), Denmark
partners including, industrial stakeholders
fermentation of SYNGAS, and the pyrolysis
(UCPH), Germany (UKE and Galab), Ireland
(represented by Unilever and Eurofins),
of high complex bio waste enabling
(NIBRT) and the UK (UNIMAN), the team is
patient groups representing people at risk
the treatment and recycling of complex
identifying new biomarkers and tools for
of severe allergic reactions from Germany,
biological and chemical wastes and raw
detection and diagnostic screening which
UK and Ireland and a risk manager and
materials in a single integrated process.
could be used to develop personalised
assessor group including the UK Food
treatment for cancer and related diseases.
Standards Agency. The project will work
In contrast, the National Centre for Text
with the clinical community, working in
Mining joins OSSMETER (Automated
SYBIL (Systems biology for the functional
measurement and analysis of open source
validation of genetic determinants of
software) working with 8 partners on
skeletal diseases) will see Professor Roy
platform development that will support
Goodacre and a consortium of world-
Further details of our live portfolio can
decision makers in the process of
class scientists, systems biologists, disease
be found in the ensuing research pages.
discovering, comparing, assessing and
modellers, information technologists
monitoring the health, quality, impact
and industrialists validate the genetic
collaboration with the European Academy
of Allergy and Clinical Immunology.
“MAGnetic Innovation in Catalysis”,
known as MAGIC. Manchester has
partnered with six Universities (Tokyo,
Freiburg, Lund, Joseph Fourier in France,
Edinburgh and Copenhagen) and five
barriers to chemical manufacture in
application of oxygen dependent enzymes
the 21st century. CHEM 21 (Chemical
in synthesis and transformation of
manufacturing methods for the 21st
alcohols), a FP7 funded project involving
century pharmaceutical industries) is
11 partners from leading European
a public-private partnership (PPP) that
companies and universities to develop new,
DirectFuel is another FP7 funded project
was launched at the end of 2012,
eco-efficient, and safer manufacturing
involving four Universities from across
led by Professor Nicholas Turner and
processes for the chemical industry and
Europe and the US, together with Chemtex
GlaxoSmithKline. This is a €26.4
end-users.
Italia and Photon Systems Instruments.
Curie Training Network of academic
European Commission under the 7th
Innovative Doctoral Programme entitled
a validated technology platform for the
and four SMEs from across Europe
by Professor Clare Mills funded by the
researchers (ESR) as part of a €3.6 million
projects are tackling some of the key
pharmaceutical companies, 13 Universities
launched at the MIB led and coordinated
Science Institute (PSI) host 12 early stage
Turner will also lead BIOOX (Developing
P4fifty is an FP7 funded European Marie
ever study of allergies was officially
Autumn 2014 will see the MIB and Photon
A number of EU and RCUK funded
million project that brings together six
8
for eco-efficient manufacturing processes
enormously across the healthcare sector.
In March 2013, the world’s biggest
companies (AZ, Bruker, TGK, Conformetrix,
and SarOMICS) with each ESR closely
linked to the international and industrial
partners who will be actively involved in
their research projects.
This exciting project aims to develop
photosynthetic microorganisms that
catalyse direct conversion of solar energy
9
Building links with China
Professors Eriko Takano and Nigel Scrutton
and currently host a number of their visiting
have recently secured funding through a
scientists and PhD students.
Synthetic Biology China Partnering Award,
co-funded by the BBSRC, the Chinese
Academy of Sciences (CAS) and the EPSRC
to partner and develop long term fruitful
relationships with Chinese scientists.
In addition we have hosted events with two
Chinese Universities (Hebei University of
Science & Technology and Jilin University) to
encourage scientific and teaching exchanges
and collaborations. We continue to welcome
We have strong links with the National
a high proportion of overseas students and
University of Defence Technology in China
postdoctoral fellows to the Institute.
Brazil beginnings
In November 2012, academics representing
hosted a reciprocal visit in March 2013 to
the nine schools that comprise the Faculty of
establish collaborations based on mutual
Engineering and Physical Sciences visited the
strengths in industrial biotechnology and
top universities in Brazil to explore research
bioenergy. This has led to several joint
synergies. MIB’s Dr Chris Blanford and Dr
funding applications and paper submissions.
Neil Dixon, two members of the delegation,
MIB researcher secures National Institute of Health grant
Dr Alexander P Golovanov from The University
normally exports the cellular mRNA from the
of Manchester has established a new and
nucleus to cytoplasm. Instead this machinery is
exciting collaboration with one of the world’s
used to export viral mRNA. Earlier NMR studies
leading virology groups, led by Professor
performed in the MIB (Tunnicliffe et al, PLoS
Rozanne Sandri-Goldin at the University of
Pathog, 2011, 7(1), e1001244) established the
California-Irvine to jointly study the molecular
first atomic-resolution structure of the complex
mechanisms behind the critical protein
between viral ICP27 and cellular mRNA factor.
interactions which lead to the herpes virus
hijacking the cell.
Institute of Health (NIH) will look into further
Herpes simplex virus 1 (HSV-1) causes a wide
details of how the assembly of multicomponent
range of diseases, from recurrent painful skin
complexes between viral and cellular proteins is
lesions to more serious conditions such as
organised and regulated, ultimately promoting
encephalitis.
viral replication. The identification of critical
Recently, studies here in Manchester led by
Professor Ruth Itzhaki suggested that HSV-1 can
be a risk factor in Alzheimer’s disease, and that
antiviral drugs might be effective at slowing
down its progress. Unfortunately, no effective
antiviral treatment is currently available, which
suppress viral replication efficiently. Finding a
‘weak spot’ in the HSV, which can be targeted
by the therapies of the future, would therefore
make a significant breakthrough.
During the infection, HSV expresses and uses a
key multifunctional protein called ICP27, which
among other regulatory functions, helps the
virus to hijack the cellular machinery which
10
This five-year project funded by the National
binding interfaces in these complexes may help
to design new drugs, which will interfere with
this complex assembly and HSV replication.
This collaborative project consists of two
complementary parts: virology and in vivo
studies will be conducted in the University of
California Irvine, in Sandri-Goldin’s group, while
high-resolution structural studies, mainly using
NMR spectroscopy, will be conducted here in
the MIB in Dr Golovanov’s group. What we
learn about ICP27 mechanism of action may be
helpful in developing drugs targeted at other
herpes viruses such as KSHV which causes
cancer as these viruses also encode ICP27
homologues.
Fig. 2.0
Image of the first atomic-resolution structure
of ICP27-REF complex (Tunnicliffe et al, PLoS
Pathog, 2011, 7(1), e1001244). Linear stretch of
viral protein ICP27 has adapted to specifically
bind to cellular mRNA export factor REF.
Copyright: Golovanov AP and Tunnicliffe RB.
GRAND
CHALLENGES
International collaborations
11
New drug treatments for Alzheimer’s –
adopting a drug repositioning strategy
inhibitors have been showing great promise in
clinical trials for patients with breast, ovarian
GlycoBioM bringing us one step
closer to understanding cancer
and prostate cancers caused by mutations in
Current drugs for Alzheimer’s can only delay
genes called BRCA1 and BRCA2. They work
A cure for cancer has become the Holy
symptoms for about six months, so new
by blocking the action of PARP – a protein
Grail for many medical researchers but
effective drugs are desperately needed.
that chemically tags areas of DNA damage
studying the changes that occur in cells
to highlight them to the cell’s DNA repair
and cell structure may bring us one step
machinery.
closer to understanding this elusive and
Several thousand chemicals safely exert a
change in the human biology and are currently
complex disease. Keeping up with the
in use for treating medical conditions. Professor
cell changes associated with cancer is no
Andrew Doig is adopting the strategy of drug
easy task. A key cancer-related cell process
repositioning to find new drug treatments by
testing to see whether any of these chemicals
are beneficial for Alzheimer’s disease. There is
precedence for this approach: Viagra™ and
BIOMEDICAL AND HEALTHCARE
Rogaine™ (a treatment for hair loss) were both
found to have desirable side effects, though
they were designed to treat other conditions.
Old drugs that are effective in cellular models for
Alzheimer’s disease can be rapidly progressed
to clinical trials in humans, since many of the
New discoveries in biotechnology are applied to medical processes that can find applications in such areas as
pharmacogenomics and drug production. The development of modern medicines requires an understanding of
molecules and networks at the molecular and systems levels which involves imaging and spatial mapping of cell
responses in health and disease and in response to drug challenges. Our research ranges from structural and
dynamic modelling of potential drug targets and their interactions including establishment of early phase drug
discovery pipelines through the challenges of systems mapping of the “virtual human”.
Degenerative disease researchers
make breakthrough in bid to find
treatment for Parkinson’s and
Huntington’s
known as glycosylation could advance our
“Obtaining the crystal structure of PARG
understanding significantly, leading to better
is a first and key step to guide and
diagnosis and smarter drugs since all cell
illuminate future drug-design efforts
surfaces, and more than half of the proteins
aimed at treating certain cancers.
in our bodies, are linked to sugar chains.
Knowing what this enzyme looks like,
and having a good idea of how it
operates, makes designing such drugs
less of a shot in the dark.”
biomolecules in cells, a process seen in many
Professor of Structural Biology
cancers. The team, led by Professor Sabine
already been done.
Flitsch, is identifying new biomarkers and
tools for detection and diagnostic screening
A few hundred drugs have been tested so far
that could be used to develop personalised
in cells and a promising hit called A-77636 has
treatment for cancer and related diseases.
been found which was first discovered in the
In cancer cells, recognition between cells
1980s, as a possible treatment for Parkinson’s
disease and cocaine addiction, by Abbott
PARG removes these chemical tags after
Laboratories, but not tested for Alzheimer’s.
the DNA damage has been repaired. So
the researchers believe that, similar to PARP
Leicester and the University of Lisbon in Portugal,
neurodegenerative diseases such as Huntington’s,
enter monkey brains when taken orally, a crucial
inhibitors, drugs designed to block the action
researchers identified the molecular structure
Alzheimer’s and Parkinson’s diseases.”
requirement for an Alzheimer’s drug. A new
of PARG could be effective in treating cancer.
A significant breakthrough has been made
took five years for the team to establish the
by scientists at the MIB towards developing
crystal structure of KMO – the first time it’s ever
an effective treatment for neurodegenerative
been done. The scientists then studied how the
diseases such as Huntington’s, Alzheimer’s and
compound UPF 648 binds incredibly tightly to
Parkinson’s. The work, published in the journal
the enzyme to act as an inhibitor. Previous studies
Nature, was led by Nigel Scrutton, Professor
with animal models of neurodegenerative disease
of Molecular Enzymology, and details how an
have showed that switching off the enzyme
enzyme in the brain interacts with an exciting
activity through drug binding should be effective
drug-like lead compound for Huntington’s
in the treatment of brain disorders. Professor
disease to inhibit its activity, demonstrating that
Nigel Scrutton said: “UPF 648 works very well
it can be developed as an effective treatment for
as an inhibitor of enzyme activity. However, in
neurodegenerative diseases.
its current form it does not pass into the brain
from the blood. The search is now on for related
compounds that can both inhibit the enzyme and
pass into the brain. Our research detailing the
molecular structure of the enzyme now enables
a search for new KMO inhibitors that are able to
cross the blood-brain barrier. This provides real
from the University of Leicester, said: “This is
a big move forward for the development of
new KMO inhibiting drugs. It is hoped that such
leading scientists to study glycosylation of
toxicity testing in animals and people, have
Abbott Laboratories showed that A-77636 can
Dr Flaviano Giorgini, the team’s neurogeneticist
project which brings together Europe’s
David Leys
hope for developing drug therapies to target
(KMO), which is found in the human brain. It
novel glyco-biomarkers) is a FP7 funded
essential steps in drug development, such as
Working with colleagues at the University of
of the enzyme kynurenine 3-monooxygenase
GlycoBioM (Tools for the detection of
company, PharmaKure, founded by Professor
Andrew Doig and Dr Farid Khan launched
in 2012 will take A-77636 forward and test
thousands of other known drugs. Hits found
in cell culture will be examined to find out how
is disturbed, leading to invasive growth
and dissemination of tumour cells. This
phenomenon is reflected in the glycans of
the cell coat, which is of particular interest to
researchers.
Lead author Dr Ivan Ahel, based at the Cancer
Research UK Manchester Institute said: “For
decades scientists have wanted to find out the
structure of PARG, but its large size makes it
very hard to produce in the lab. By studying
“Recombinant glycan receptors are used
a smaller version of PARG found in bacteria,
to identify tumour associated changes
we’ve been able to create a ‘3D map’ that
of the glycans in the cell coat of tumour
researchers can use to understand more
Huntington’s disease research team at University
cells. The recombinant receptors are
about how PARG works. The next step will
College London’s Institute for Neurology.
used in different ways, such as for
be to investigate whether drugs that block its
identifying tumour associated changes
activity might be an effective way of treating
to carcinoma cells in tissue sections,
cancers driven by faults in DNA repair genes.”
and recognising sub-populations of
compounds may ultimately be tested in clinical
trials and prove beneficial for patients.”
Professor Sarah Tabrizi is the head of the
Commenting on the research she says:
“Unlocking the crystal structure of KMO is a
real boost to our efforts to find treatments for
this devastating disease. It provides a solid basis
for the optimisation of inhibitor drugs like UPF
648 that are being developed by the global
Huntington’s disease research community. KMO
is one of our top drug targets, and the crystal
structure is a significant step along our roadmap
to clinical trials of KMO inhibitors in patients.”
they work and then tested in mouse models
of Alzheimer’s and, if successful, ultimately in
human volunteers with Alzheimer’s.
Bacteria to shed light on new
drug targets for inherited
cancers BRCA1 and BRCA2
leukaemia cells. The GlycoBioM team
Scientists at the MIB and the Cancer Research
Handling of protein crystals for x-ray
is also using the receptors to identify
UK Manchester Institute have succeeded in
crystallography
soluble glycobiomarkers in tumour
purifying a protein found in bacteria that
could reveal new drug targets for inherited
breast and ovarian cancers as well as other
cancers linked to DNA repair faults.
patients’ blood samples”.
Professor Christoph Wagener
University Medical Center HamburgEppendorf (UKE), Germany
The team are the first to decipher the
A cartoon representation of Saccharomyces cerevisiae kynurenine 3-monooxygenase (KMO). Inhibition of KMO, an enzyme in the
12
structure of a protein called PARG, which
eukaryotic tryptophan catabolic pathway, leads to amelioration of Huntington’s-disease-relevant phenotypes. The figure shows a flavin
plays an important role in DNA repair and
adenine dinucleotide (FAD) highlighted in red (stick representation) with the cocrystallised inhibitor UPF-648 depicted as purple spheres.
acts in the same pathway as PARP. PARP
13
In parallel, project members from The
to visit hospital for lengthy infusions. The
structural parameters governing their stability
between high and low risk disease will direct
virus from the bloodstream. Telaprevir™,
University of Manchester, in collaboration
challenge for bioprocessing research is to
in order to help solve this problem. In a
research towards novel molecular markers
which was launched in 2011 by Vertex, is
with the University of Liverpool, have been
dissolve the dose of protein required in a
related project, Dr Blanch is also working
that may shed light on tumour progression
currently the leading medicine in this area
working on an analytical tool to capture and
small volume to enable self-injection. This
with Professor Andrew Doig to develop these
as well as generating new molecular
although in order to make it widely available
characterise glycan binding proteins which
challenging project will be led by Dr Xue-
spectroscopic tools for detailed structural
diagnostic markers for use in the clinic.
at an affordable cost it is necessary to
could eventually be used to pinpoint sugar
Feng Yuan, Reader in Biochemical Physics in
analysis of proteins and UCB Pharma are
biomarkers in diseases such as cancer.
collaboration with MIB colleagues Dr Robin
now supporting this research.
This project has also progressed our
Curtis and Dr Alexander Golovanov from
corresponding study which brings together a
critical mass of scientists from the Universities
MIB and Dr Alistair Revell from the School of
develop inexpensive manufacturing routes
Expanding their work on cytochrome
to the molecule. Professor Nicholas Turner,
P450 enzymes Professors Andrew Munro
in collaboration with Professor Romano Orru
and David Leys together with Dr Kirsty
at the Free University of Amsterdam, has
McLean will adopt a fragment based
devised an efficient synthesis of Telaprevir™
screening approach (FBS) to rationalizing
which combines biocatalysis with multi-
Mycobacterium tuberculosis (Mtb) P450
component chemistry.
molecular selectivity.
Towards disease diagnosis
through spectrochemical
imaging of tissue architecture
of Cardiff, Lancaster, Liverpool and Manchester
to check for maturity-onset diabetes of the
More than a quarter of a million people are
to advance the understanding, diagnosis
Initially an engineered biocatalyst
Cytochrome P450 enzymes are a superfamily
young (MODY), a form of diabetes that is
diagnosed with cancer annually in the UK
and treatment of cervical, oesophageal
(monoamine amine oxidase), which has been
of oxygenases that perform an array
caused by mutations in a number of different
and the four most common ones, breast,
and prostate cancers. Cervical and prostate
optimised by successive rounds of directed
of physiologically important reactions
lung, bowel and prostate, make up over half
cancers are very common and the incidence
evolution, is used to convert a cheap achiral
in organisms from bacteria through to
of all these cases. Many, such as prostate
of oesophageal is rising rapidly. There are
starting material to an optically pure chiral
man, including steroid and bioactive lipid
cancer correlate strongly with age, with 77%
cytology, biopsy and endoscopy techniques for
building block. Thereafter this building block
syntheses, and xenobiotic transformations.
of cases being diagnosed in men over the
extracting tissue from individuals who are at
is used in a three-component Ugi reaction
With increasing numbers of P450 (CYP)
age of 55. There is a clear clinical need for
risk of developing these diseases but there is
resulting in a highly convergent synthesis
genes identified from genome sequences,
a robust and preferably automated system
a national and international need to develop
of Telaprevir™. The groups in Manchester
it is apparent that there is a large untapped
which can not only facilitate the pathological
more accurate diagnostics for these diseases.
and Amsterdam have patented this route,
resource of uncharacterized oxidase enzymes
in addition to publishing several papers,
of unknown specificity. In M. tuberculosis
and have recently licensed the technology
(Mtb) there are 20 P450s, with substrates
to a pharmaceutical company who plan to
definitively identified for six. This project
exploit the technology for the manufacture
will exploit and develop fragment based
of Telaprevir™.
screening (FBS) technology to identify small
understanding of diabetes, in particular
the discovery of a novel glycan biomarker
related to the disease, and the team expects
Mechanical, Aerospace and Civil Engineering
(SMACE).
to develop a system that will enable patients
genes.
The GlycoBioM project is truly a European
success story, with partners from opposite
ends of Europe all contributing to groundbreaking results. When the Croatian team
found that certain glycans can predict the
speed at which colon cancer will progress
diagnosis but also to discriminate between
(which could lead to tailored therapy – or
‘smart drugs’ – for individual patients), the
Danish team took up the baton, developing
a new glycoprofiling method to reduce falsepositive cancer diagnoses. This is expected
to help women with ovarian cancer. Apart
from having developed a new blood test
for ovarian cancer, the team has made
commendable progress in unravelling the
complexities of breast cancer and it is hoped
that these results lead to better stratification
of patients regarding the choice of the
most appropriate therapy. This project
also featured in the Royal Society Summer
Exhibition – see Science and Society section.
Tackling the manufacture of
concentrated protein medicines
Future trends in treating various chronic
diseases with recombinantly-produced
therapeutic proteins (such as monoclonal
14
Professor Gardner is involved in a
A fragment based screening
approach to rationalizing M.
tuberculosis P450 molecular
selectivity
tumours of low risk, which require
Funded by the BBSRC this project aims to
surveillance or less aggressive treatment,
develop methods for use by industry to
and those of high risk, which will progress
screen protein formulations for viscosity and
more rapidly and which need aggressive
other flow properties, using small quantities
intervention to prevent morbidity and death.
of protein. This will enable methods for
We have shown previously in small scale
viscosity reduction to be developed. The
studies that infra red spectral markers used
team will apply comprehensive rheological
in conjunction with algorithmic models
characterisation, RheoChip rheometry, and
can be utilised not only to provide tumour
advanced modelling as a platform, which
grading data but also to provide staging and
can be used by industry to select the protein
prognostic information.
and formulation for development of the
and clinicians from the Christie, Lancaster
and Liverpool NHS Hospital Trusts with the
complementary experience and expertise
Experiments will be conducted on specimens
from all three diseases using four different
infrared based techniques which have
complementary strengths and weaknesses:
hyperspectral imaging, Raman spectroscopy,
molecule ligands that bind to the active site
a new instrument to be developed by
combining atomic force microscopy with
infrared spectroscopy and a scanning near
field microscope recently installed on the free
electron laser on the ALICE accelerator at
of a panel of key Mtb P450 enzymes (using
Characterization of a superior
biocatalyst for pravastatin
production
X-ray crystallography to define the binding
modes). It will then use a combination
of chemical elaboration and ‘merging’ of
fragments binding at adjacent positions, to
Daresbury. This combination of techniques
Andrew Munro, Professor of Molecular
will allow the team to probe the physical and
iteratively improve their efficiency of binding
Enzymology and Research Associate Dr
and potency as inhibitors and as probes
final dosage form, at an earlier stage than
The attraction of infrared spectroscopy to
chemical structure of these three cancers
Kirsty McLean, together with industrial
aid clinical diagnosis is that it is a widely
with unprecedented accuracy revealing
of structural/catalytic features of targeted
is possible today saving time and money
partner DSM, have used directed evolution
in the development of many new protein
important information about their character
P450s. This will generate novel libraries
known technology which is readily available,
and structural biology in order to redesign
reliable, simple to use and relatively
and the chemical processes that underly their
containing fragments representing both
medicines. The research will build on existing
an enzyme catalyst (a cytochrome P450) in
inexpensive. It also allows further post
malignant behaviour.
likely substrates classes for P450s (fatty acids,
methods, which are already well established
order to alter its substrate specificity and to
steroids, polyketides) and unusual lipids
for rheological characterisation of water
scanning interrogation because it does
enable it to convert a natural product into
prevalent in and/or peculiar to Mtb, and then
soluble polymers and BSA solutions, and
not destroy the tissue under investigation.
the cholesterol-lowering drug Pravastatin™
exploit FBS with these libraries to generate/
adapt and apply them to the bioprocessing
The aim of this EPSRC funded proposal
in a single step. The synergistic efforts
identify physiologically relevant substrate-
and injectability of high concentration
is to adapt existing technologies and
of industrial researchers at DSM, experts
like molecules, with reference to active site
protein biopharmaceutical solutions.
protocols using spectroscopic analysis of
in microbial fermentation and screening
structure of the target P450s and knowledge
techniques, together with the Munro
of the metabolomics of Mtb.
cancer tissue to develop rapid and accurate
antibodies) require frequent and high
Dr Ewan Blanch, Reader in Biophysics,
doses of an active protein ingredient in a
systems of analysis, which can be applied
has been working on an EPSRC-funded
small volume of liquid (e.g. >100mg/ml for
to the identification and characterisation of
project with Dr Stavroula Balabani, a fluid
subcutaneous (SC) injections using a prefilled
dynamics engineer at UCL, to investigate
syringe or auto-injection device). There is a
the destabilisation of a protein structure
need for underpinning research to support
by shear force typically experienced by
industrial development of novel protein
protein therapeutics during bioformulation.
therapeutics for more convenient delivery of
The aggregation of protein therapeutics
biological tissues using prostate cancer as the
primary model. Using this system Professor
Peter Gardner, in collaboration with the
Cancer Research UK Manchester Institute,
will develop a model, which can distinguish
between low and high risk prostate cancers
products by subcutaneous injection. This is
(biologics) is a major problem for the
an increasing priority for biopharmaceutical
in samples that have been previously graded.
pharmaceutical sector and Dr Blanch and
companies enabling patients to administer
An added benefit of spectral screening is
colleagues are developing Raman and
medicines at home, rather than having
that interrogation of the spectral differences
infrared spectroscopies to understand the
Developing technologies
to produce inexpensive
pharmaceuticals
Hepatitis C is a major global health problem
that currently affects approximately 200
million people worldwide. Many of the
infected people live in countries where access
to modern expensive treatments is a major
issue. Recently a new class of drugs has
been developed that are highly effective in
tackling the infection and in the majority of
patients result in complete removal of the
group, experts in enzymology and protein
crystallography, led P450 catalysts to
This project exploits FBS, structural biology,
perform the desired reaction with much
synthetic chemistry and various spectroscopic
greater stereoselectivity than other chemical
methods to generate novel inhibitors for
or enzyme-based approaches. This new
Mtb P450s involved in cholesterol oxidation
biotechnologically advanced method forms
and secondary metabolite synthesis, to
the basis of a patented process for efficient
identify substrates for ‘orphan’ P450s to
production of this blockbuster drug.
enhance knowledge of the biochemistry of a
biomedically important bacterium.
15
Developing a technological
platform for the design of novel
biomaterials
of these materials. When used as structural
In a project that will contribute significantly
Dr Saiani is currently developing this
to the field of healthcare technologies as
technological platform by furthering our
well as biomaterials and tissue engineering
understanding of the self-assembly process
research Dr Alberto Saiani, Reader in
of these short peptides and designing novel
Molecular Materials, has received an
responsive and increasingly functional
EPSRC Research Fellowship to develop a
materials for a new field of applications.
technological platform for the design of
novel biomaterials that can be used across
a number of applications. The use of
non-covalent self-assembly to construct
World’s biggest ever study of
food allergy gets underway
peptide required is significant.
Through engagement with academic
and industrial end-users throughout the
development process the team will ensure
that the materials designed will be relevant
The Manchester team will work with 38
Dr Bert Popping, Eurofins Scientific Director,
materials has become a prominent strategy
partners including, industrial stakeholders
said: “Eurofins is excited to be part of this
in materials science offering practical routes
(represented by Unilever and Eurofins),
European Commission project. We are
Up to 20 million European citizens suffer
for the construction of increasingly functional
patient groups representing people at risk of
looking forward to sharing our newly-
from food allergy, a disease that can be
materials for a variety of applications ranging
severe allergic reactions from Germany, UK
developed multiple allergen detection
conquered, if critical steps are taken. However,
from electronic to biotechnology. A variety
and Ireland and a risk manager and assessor
method and making a meaningful
management of both food allergy, by patients
of molecular building blocks can be used
group including the UK Food Standards
contribution to this crucial initiative.”
and health practitioners, and allergens, by
for this purpose such as de-novo designed
MIMIT (Manchester: Integrating Medicine
Agency. The project will work loosely
industry, is thwarted by lack of evidence to
peptides. With a library of 20 natural amino
and Innovative Technology) has celebrated
with the clinical community, working in
either prevent food allergy developing or
acids available it offers the ability to play
its four year anniversary during which time
collaboration with the European Academy of
protect adequately those who are already
with the intrinsic properties of the peptide
it has developed 27 projects, requiring
Allergy and Clinical Immunology.
such as structure, hydrophobicity, charge and
£1million initial investment (project and
This €9 million project builds on an earlier
functionality allowing the design of materials
infrastructure), based on 116 unmet clinical
€14.3 million research study EuroPrevall also
with a wide range of properties.
needs. To date projects have leveraged
allergic. European Commission-sponsored
research, known as the Integrated Approaches
This study involves 38 partners and is headed
to Food Allergen and Allergy Risk Management
by MIB’s Clare Mills, Professor of Allergology,
(iFAAM), will set the stage for facilitating such
from the Allergy and Respiratory Centre
steps to be taken. This research will produce
of The University of Manchester’s Institute
a standardised management process for
of Inflammation and Repair. Based in the
companies involved in food manufacturing.
Manchester Institute of Biotechnology.
It will develop evidence-based approaches
Professor Mills said: “This is a massive
and tools for the management of allergens
research project that will have far reaching
in food and integrate knowledge derived
consequences for consumers and food
from their application and new knowledge
producers. The evidence base and tools that
from intervention studies into food allergy
result from this will support more transparent
management plans and dietary advice. The
precautionary “may contain” labelling of
resulting holistic strategies will reduce the
allergens in foods which will make life easier
burden of food allergies in Europe and beyond,
for allergy sufferers as they try to avoid
whilst enabling the European food industry to
problem foods.”
compete in the global market place.
iFAAM kick-off meeting held in November 2013 at the MIB
16
materials, as in hydrogels, the quantity of
This research study featured in the BBC series
“Trust Me I’m A Doctor” presented by Dr
Michael Mosley.
headed by Professor Mills which involved 62
partners from 17 countries.
The main challenge facing scientists in this
field is being able to rationally design these
Professor Mills was recently elected to the
peptides to gain control over the physical
International Academy of Food Science
properties of the resulting self-assembled
and Technology, a distinguished group of
materials. This requires not only an in depth
outstanding scientists representing the
knowledge of the self-assembling processes
international community of food science
at all length scales, but also a detailed
and technology. The induction ceremony for
understanding of the specific requirements
new Fellows took place at the IUFoST* World
of each application targeted. For example,
Congress of Food Science and Technology
injectable materials need to be developed
held in Iguassu Falls, Brazil.
for cell delivery while for drug delivery oral
cavity sprayable systems could be required.
*International Union of Food Science and Technology
For cell culture and tissue engineering the
whilst exploring new potential fields of
application.
MIMIT celebrates 4 years
£3million, 3 clinical research fellowships,
numerous publications and patents. One of
the first developments reached the market
place mid-2013 and resulted in 1 licence
agreement with a SME, £5m VC funding
and 1% estimated net returns of $250m
per annum. Royalty returns will be shared
between the NHS, academia and inventors.
Two other project have leveraged £2million
VC and £5million Pharma investment
between them and 9 projects have received
UMIP Proof of Principal investment to get
them ‘investor ready’.
issue of adaptability of material properties
One of the early projects supported by MIMIT
is even more critical as depending on cell
Phagenesis won Bionow Healthcare Project
type, origin and intended behaviour, cells
of the year 2012. Congratulations also went
have very different requirements in terms
to Curtis Dobson, MIMIT Site Miner for the
of the environment, (ie. material properties
award of Biomedical Project of the Year 2012
and functionality) in which they are placed.
to Microsensor, a novel infection sensing
Finally, one other key element is the cost
technology.
17
amines, oligosaccharides and renewable
Biocatalytic tools for industry
polymer intermediates which are better in
INDUSTRIAL BIOTECHNOLOGY
Industrial Biotechnology (IB) is a set of cross-disciplinary technologies that use biological resources, such as algae,
plants, marine organisms, fungi and micro-organisms, for the production and processing of chemicals, energy and
materials. A multidisciplinary approach is essential to transform the traditional chemical and chemical-related sector
to a more sustainable and competitive one which draws on disciplines such as organic and synthetic chemistry,
biochemistry, molecular biology, enzyme kinetics, genomics, proteomics, bio-informatics and bioprocessing.
With major recent grant awards in Industrial Biotechnology and strategic participation in national and international
forums over the past year, the widely recognised expertise in IB@MIB has seen major research programmes initiated.
“This research will yield substantive
advantages to the scientific
community involved in industrial
biotechnology. The Manchester
Institute of Biotechnology is a
recognised leader within this field
and represents a strong partner
for the synthetic biochemistry
18
Professor Nicholas Turner will also lead
complexity and /or specificity of the synthetic
BIOOX (Developing a validated technology
pathways than those currently employed. The
platform for the application of oxygen
This project is led by Professor Jason
consortium consists of 17 institutions from
dependent enzymes in synthesis and
Micklefield, in collaboration with Professors
university research groups, small and medium
transformation of alcohols), a collaborative
David Leys and Nicholas Turner, and is
sized companies, to BASF, the world’s leading
FP7 project involving 11 partners from
funded by BBSRC and BASF through the
chemical company.
leading European companies and universities
Industry Partnership Award (IPA) Scheme.
to develop new, eco-efficient, and safer
The MIB team used structure-guided
The consortium have identified the key
manufacturing processes for the chemical
directed evolution to create new malonate
technology fields of amine synthesis, polymers
industry and end-users. This programme will
decarboxylase enzymes that can produce
from renewable resources, glycoscience and
develop the tools for the implementation
a wide range of carboxylic acids, which
wider oxidase application as four key areas
of biooxidation to synthesize and oxidize
are particularly common intermediates
where the next generation of biocatalysts
alcohols for applications in flavourings and
in the manufacture of pharmaceuticals,
that will lead to improvements in both
fragrances, and fine chemicals. The aerobic
agrochemicals and other valuable products.
economic and environmental performance
biocatalytic oxidation reaction currently has
The new decarboxylase enzymes are
of the chemical manufacturing industries.
the potential for the biggest impact on the
also attractive because the substrates
This programme, funded under the EU 7th
future uptake of industrial biotechnology (IB)
can be generated from malonic acid, a
Framework Programme, will enable industry
in Europe. Bioprocesses have the potential
natural precursor derived from renewable
to use renewable resources with reduced
to overcome the hazardous nature and
sources (fermentation). The availability
greenhouse gas production as compared
high environmental impacts of current
of chiral carboxylic acids, which are
to their fossil counterparts and deliver
chemical oxidation processes. Biocatalysis for
single enantiomers (one of two possible
biotechnological routes with reduced energy
oxidative chemical manufacture processes
stereoisomers that are non-superimposable
consumption and less toxic wastes compared
can deliver a major advantage to the
mirror images) is of critical importance
to conventional chemical processes. Routes to
European chemical-using industries and the
particularly for pharmaceutical production.
specialised, high-value chemicals (e.g. chiral
environment, and it is expected that this
chemical compounds) normally require long
Fig. 3.0
new technology platform will allow the rapid
chemical synthetic routes involving complex
development of bio-oxidations as a routine
reaction steps with toxic side products and
technology for the IB industry and support
waste streams. This project will allow these
the European knowledge based bioeconomy.
methods to be replaced by clean biocatalysis
The four-year, €7.4 million project will be
routes. To broaden the range of fine and
promoted by a dynamic public engagement
speciality chemicals and intermediates
and dissemination programme within the
Industrial chemicals of the
monoterpenoid class realised
through synthetic biology and
pathway engineering
By essentially mimicking the process of
produced by biotechnological routes, research
scientific community and the wider public,
Darwinian evolution in the laboratory this
In partnership with GSK, Professors Nigel
will address 1. the design and optimisation
especially schoolchildren, to create extra
interdisciplinary team will develop a new
Scrutton, John Gardiner, David Leys and Pedro
of enzymes to be used in synthetic chemistry;
value for the European Union.
approach to engineering robust biocatalysts
Mendes have engineered bacterial strains to
2. the selection/development of modified
that will enable the optimisation of enzymes
produce flavours and fragrances that belong to
microorganisms which are resistant to
In collaboration with GlaxoSmithKline,
for industrial applications in a matter of weeks
the monoterpenoid family of compounds using
heat, pressure or low pH when used in the
one of the world’s largest pharmaceutical
rather than the months it currently takes,
synthetic biology and enzyme engineering
production of chemical entities and allow 3.
companies, this project seeks to develop an
resulting in a much greener approach to the
approaches.
the integration of biotechnological steps into
accelerated laboratory evolution platform
production of a wide variety of products.
conventional chemical processes.
for the rapid optimisation of biocatalysts
for industrial application in target molecule
synthesis.
This £5M project is funded under the BBSRC
sLoLa initiative in partnership with GSK.
Expertise has been compiled from seven
biotechnologies. Being able to
diverse research groups based at the
engineer bespoke biocatalysts more
MIB under the leadership of Nicholas
efficiently will result in a much
Turner, Professor of Chemical Biology and
wider application to our chemical
Director of CoEBio3. Leading other work
BIONEXGEN, led by Professor Nicholas
manufacturing processes, and
packages within this grant are Professors
Turner, will develop the next generation
support our research into new
Sabine Flitsch (glycomics), Roy Goodacre
of biocatalysts to be used for eco-efficient
medicines.”
(metabolomics), David Leys (crystallography),
manufacturing processes in the chemical
Jason Micklefield (synthetic biology and
industry. It will also develop and integrate,
biocatalysis), Nigel Scrutton (enzymology)
with chemical steps, the biotechnological
and Dr Claire Eyers (mass spectrometry,
manufacturing routes for the synthesis
University of Liverpool).
of fine and speciality chemicals especially
GlaxoSmithKline
terms of eco efficiency, economic potential,
Rapid evolution of enzymes and
synthetic micro-organisms for
the development of industrial
biocatalysts
team at GSK to develop new
Dr Joe Adams
Directed evolution of
enantiocomplementary
malonate decarboxylases
Developing next generation
biocatalysts
Fig. 3.0
Structure-guided directed evolution of
alkenyl and arylmalonate decarboxylases.
19
Bio- or ‘natural’ routes to the synthesis of
pharmaceutical company GlaxoSmithKline.
of biosynthetic gene clusters to discover
these compounds significantly enhance their
The introduction of biotechnology to the
novel natural products. Natural products are
market value and this research will transform
manufacturing processes for medicines will
small molecules produced predominantly by
the industrial production of monoterpenoid
limit the drain on the world’s resources and
microorganisms and plants that have inspired
synthesis by providing ‘natural’ routes to these
have a lasting benefit on the environment.
the development of many blockbuster drugs
compounds, avoiding problems associated
with classical chemical synthesis. Bio-routes will
reduce the environmental impact associated
with classical synthesis and release industry
from the constraints of limited availability from
natural resources. This project is funded by
the BBSRC as part of the Industrial Partnership
Award (IPA) Scheme.
Pharmaceuticals and universities
working together on multi
million pound project
Europe’s largest public-private partnership
(PPP) dedicated to the development of
manufacturing sustainable pharmaceuticals
was launched at the end of 2012 and is
led by Professor Nicholas Turner and the
including anticancer and immunosuppressive
CHEM21 brings together six pharmaceutical
companies, 13 Universities and four small
“Improving the sustainability of our
to medium enterprises from across Europe
drug manufacturing processes through
in a £21.2 million project with the aim
collaborations such as CHEM21 will
of developing sustainable biological and
not only reduce our industry’s carbon
chemical alternatives to finite materials, such
footprint, but will provide savings that
as precious metals, which are currently used
can be reinvested in the development
as catalysts in the manufacture of medicines.
of new medicines, increase access to
CHEM21 will run initially for four years
with funding from the Innovative Medicines
Initiative. The project will establish a
European research hub to act as a source of
medicines through cost reduction and
drive innovations that will simplify
and transform our manufacturing
Dr John Baldoni
It will also develop training packages to
GlaxoSmithKline
Manchester and Professor John Ward
(University College London)
clinical use today. Natural products are also
This network aims to develop new tools to
used in agriculture as herbicides, pesticides
accelerate biocatalyst research, discovery
and fungicides to increase crop yields. In
and development. The network will provide
addition, bioengineering methods and
the framework and coordination to allow
synthetic biology tools will be developed
research groups from industry and academe
to enable rapid structural diversification
to easily access and develop a truly broad
and optimisation of the most promising
range of biocatalyst panels and technologies
natural product molecules for therapeutic,
for screening whilst providing a pipeline
agrochemical and other applications.
through to scale-up, manufacture and
commercial use of novel enzymes.
ensure that the principles of sustainable
manufacturing are embedded in the
education of future scientists.
“These networks bring together
“The networks will drive new ideas
a number of internationally
to harness the potential of biological
competitive, cross-disciplinary
resources for producing and processing
communities capable of
materials, biopharmaceuticals,
undertaking innovative research
chemicals and energy. Each has a
that will attract further investment
particular focus, such as: realising
from the UK and abroad. They
the potential of food waste and by-
provide a new opportunity for
products to produce chemicals and
the research community to make
biomaterials; unlocking the industrial
significant contributions to the UK’s
biotechnology potential of microalgae;
bioeconomy: driving transformational
between the academic research base and industry, promoting the translation of research into benefits for the UK. The
producing high value chemicals from
bioscience into industrial processes
University of Manchester secured four networks, three of which will be led from MIB. These national networks pool skills
plants; and making use of plant cell
and products; creating wealth and
from academia and business to develop research projects with the potential to overcome major challenges in the industrial
walls (lignocellulosic biomass) to
jobs; and delivering environmental
produce chemicals and biofuels.”
benefits, such as CO2 reduction.”
David Willetts
Dr Celia Caulcott
Minister for Universities and Science
BBSRC Executive Director, Innovation
Industry-academia networks in industrial biotechnology and bioenergy
The Biotechnology and Biological Sciences Research Council (BBSRC) announced in December 2012 an investment of
£18million in 13 unique collaborative ‘Networks in Industrial Biotechnology and Bioenergy’ (BBSRC NIBB) to boost interaction
biotechnology and bioenergy arena whilst allowing new members to come on board with skills that can benefit the group.
IBCarb - Glycoscience tools for
biotechnology and bioenergy
Professor Sabine Flitsch, University of
Manchester and Professor Rob Field, John
Innes Centre
Carbohydrates constitute the largest source
of biomass on Earth and their exploitation
for novel applications in biomaterials, energy,
food and health will be critical in moving
away from dependence on hydrocarbons
to develop sustainable biotechnologies and
reduce GHG emissions, ensuring both energy
and food security. Glycoscience is a broad
term used for all research and technology
involving carbohydrates, ranging from cell
biology, human nutrition and medicine
to carbohydrate-based materials and the
conversion of carbohydrates to energy.
20
Professor Nicholas Turner, University of
agents including most of the antibiotics in
paradigm”
up-to-date information on green chemistry.
Network in biocatalyst
discovery, development and
scale-Up
The analysis, synthesis and biosynthesis of
polysaccharides) or energy (digesting the
carbohydrates and their modification to
indigestible). IBCarb is an interdisciplinary
industrial products are, therefore, central
network that will allow for exploitation of
challenges in both industrial biotechnology
opportunities presented by Glycoscience.
and Skills
and bioenergy.
The last twenty years have seen a number of
to carbohydrate synthesis and modification,
Natural Products Discovery
and Bioengineering Network
(NPRONET)
enzymology and glycomic analysis. At the
Professor Jason Micklefield, University of
same time, there is a technology pull -
Manchester and Professor Barrie Wilkinson,
great demand and opportunities in diverse
John Innes Centre
fundamental changes in the glycosciences
generating a technology push with respect
areas such as biopharmaceuticals (8 out
of 10 top selling drugs worldwide are
glycoproteins), foods (prebiotics designed for
the human gut microbiota), antimicrobials
(targeting cell surface recognition and
biosynthesis), materials (from biorenewable
Building on the UK’s established worldleading expertise in natural product
chemistry, biosynthesis and microbiology
Working closely with industry to advance the field of chemical biology
Funded by EPSRC, BBSRC and MRC and with commitments from its 10 industrial partners, the
Manchester Chemical Biology Network brought together more than 50 research groups from
a range of disciplines across The University of Manchester to share expertise with industrial
partners, including companies such as AstraZeneca, GSK and Pfizer.
Professor Jason Micklefield and Professor
This collaboration between research groups provides a more effective platform to tackle the major
Barrie Wilkinson will lead this network
challenges associated with the discovery of new drugs and other products of importance to human
devising methods to activate the expression
health and wellbeing, using expertise ranging from synthetic chemistry through to cell biology.
21
and propane in photosynthetic cyanobacteria
the environmental benefits and drawbacks
targeting only non-toxic end-products that
related to the concept. The knowledge
have been demonstrated to function in
generated through this innovative
existing or minimally modified combustion
biotechnological approach will not only
engines.
benefit the environmental management
As no natural biochemical pathways are
known to exist for short-chain alkane
biosynthesis, it is necessary to identify
potential gene candidates through
In its first phase (funded to >£6M by
informatics analysis and then tailor the
the BBSRC and EPSRC) the Manchester
substrate specificities of the encoded
Centre for Integrative Systems Biology
enzymes by enzyme engineering. In order
(MCISB) prepared a complete toolbox
Photosynthetic organisms are able to
to directly capture solar energy to drive fuel
from computational analyses through
utilize water, CO2 and sunlight to directly
biosynthesis, the synthetic pathways are at
experimental approaches to data handing
synthesize fuel or chemical precursors - all in
first assembled in the photosynthetic model
and organisation. The results of this early
one engineerable package capable of both
organism Synechocystis sp. PCC 6803. To
research can be found in a set of web
self-amplification and internal self-repair.
deliver the energy reduction and metabolic
resources and in the most recent issue of
Terrestrial-grown plants however display poor
precursors to the synthetic pathways with
Methods in Enzymology devoted to Systems
overall solar energy conversion efficiency.
maximum metabolic flux it is essential
Biology by the MCISB.
An alternative to land-based biomass
Successful construction of the intended
are aquatic photobiological organisms,
strains will allow low-cost production
eukaryotic algae or cyanobacteria. These
of transport fuel in a potentially neutral
organisms display simple nutritional
‘greenhouse gas’ emitting process that does
requirements and are in some cases even
not compete for agricultural land.
cable of nitrogen fixation.
is not suitable for agriculture in constructed
enclosed systems that do not utilize soil.
Bacteria making “oil”
aspects of energy including fuel cells, solar
Solutions that seek to reduce our
scope for application of these components,
energy and 2nd/3rd/4th generation biofuels.
dependency on fossil oil are being tackled
and engineered variants thereof, in the
Research into alternative biofuels includes
by Professors David Leys, Andrew Munro
production of drop-in biofuels, provided
utilising biomass from both agricultural and
and Nigel Scrutton who are working on
high-levels of alkane production can be
marine sources to the development of novel
a BBSRC Industry Partnership Award with
achieved at competitive costs.
biocatalysts.
Shell combining state-of-the-art enzymology
and laboratory evolution techniques with
An industrial award with Shell will challenge
Fill your car with petrol or diesel today, and
synthetic biology to make organisms produce
this same research team with the scoping
the fuel you buy will likely contain a small
“oil”, bypassing the need to drastically adapt
of natural variants as well as laboratory-
(5%) proportion of biofuel. Could we use
oil-dependent processes. The team will focus,
evolution of the most promising variants
more and limit our reliance on fossil fuels?
in particular, on production of linear alpha-
towards applicable alkane producing
Almost certainly yes but current biofuels are
olefins, a high value, and industrially crucial
enzymes.
not fully compatible with modern, mass-
intermediate class of hydrocarbons that
market internal combustion engines. The
are key chemical intermediates in a variety
cost of modifying vehicles and fuel supply
of applications. At present, no “green”
infrastructure, to run on blends containing
alpha-olefin production process is available, a
20% or more bioethanol or biodiesel is the
situation which this project seeks to change.
Aquatic photobiology –
exploring the potential
Biological fuel production is already a
is to produce a biodiesel with the same
commercial reality with biology expected to
Alkane producing enzymes
contribute further towards fuel-production
The production of alkanes in nature has
systems, particularly with the advancement
been documented for a limited set of
in technologies that enhance economic
organisms, with many of the molecular
sustainability.
in commercial volumes. Biofuels with these
characteristics are being termed ‘drop-ins’.
By choosing aquatic instead of terrestrial
systems for harvesting sunlight it should be
possible to minimize the potential conflict
between food-producing agriculture and
photobiological fuel production. Aquatic
photobiological organisms are also capable
of potentially greater solar energy conversion
efficiency compared to terrestrial plants.
This EU FP7 collaborative project involves
four Universities from across Europe and
the US, together with Chemtex Italia and
Photon Systems Instruments with the aim of
developing photosynthetic microorganisms
that catalyze direct conversion of solar
energy and carbon dioxide to engine-ready
major limiting factor. The grand challenge
chemical structure as conventional diesel fuel
22
components underpinning these processes
only recently identified. There is obvious
focuses in particular on the biological
in both intermediate and future energy
The MCISB continues to be involved in two
Biotechnology Research Industry Club (BRIC)
projects funded by the BBSRC (on protein
production in various microorganisms using
various feedstocks), as well as by a large
number of other BBSRC and EU grants under
the leadership of Professors Hans Westerhoff,
The cultivation of eukaryotic algae or
cyanobacteria can be carried out on land that
Our contribution to the energy agenda
petrochemical plastics.
photosynthesizing cyanobacteria which are
to optimize the native host metabolism.
During the next two decades the chemical industry will undergo a major transformation. As both oil and natural
gas begin to run out, there will be a growing need to switch from oil based starting materials to those derived
from biomass. Biotechnology-based processes will need to be developed to efficiently convert inexpensive raw
materials to high-value products such as pharmaceutical drugs, cosmetics and fuels. From underpinning strategic
research to the transfer of technology into the marketplace, The University of Manchester has a range of worldclass activities supporting the need for solutions that can play their part in meeting the global energy challenge.
the harmful environmental impact of
Aquatic photobiology – cultures of
the hosts for alkane production
BIOFUELS and ENERGY
of terrestrial wastes, but also reduce
fuels.
SYNPOL – Biopolymers from
syngas fermentation (SYNPOL)
Pedro Mendes and Dr Jacob Snoep.
SYNPOL is an EU FP7 KBBE collaborative
IONTOX Safe green solvents for
the future
project (Knowledge-Based Bio-Economy
(KBBE)) involving 14 European partners from
academia and industry. The basic idea of
the SYNPOL project is the establishment
of an integrated processing technology
for the efficient synthesis of cost-effective
commercial new biopolymers using the
products derived from fermentation of
SYNGAS generated from very complex
feedstocks. This revolutionary project will
see the establishment of a platform which
integrates biopolymer production through
modern processing technologies, with
bacterial fermentation of syngas, and the
pyrolysis of highly complex biowaste (e.g.,
municipal, commercial, sludge, agricultural)
enabling the treatment and recycling of
Fuel production should not require
complex biological and chemical wastes and
destructive extraction and further chemical
raw materials in a single integrated process.
conversion to generate directly useable
transport fuels. The DirectFuel consortium,
represented by Professors Nigel Scrutton
and David Leys from Manchester, chose to
develop an exclusively biological production
process for the volatile end-products
ethylene and short-chain n-alkanes ethane
R&D activities will be focused on the
integration of innovative physico-chemical,
biochemical, downstream and synthetic
technologies to produce a wide range of
new biopolymers, based on a number of
novel and mutually synergistic production
methods, and including an assessment on
In silico predictive chemometric models for
selected toxicity endpoints of ionic liquids
Ionic liquids (ILs) are a modern addition to
the world of chemical compounds, deployed
in areas ranging from electrochemistry, over
organic synthesis, to cleaning, extraction
and separation technology. Their unique
negligible vapor pressure, non-flammability,
enhanced thermal stability and outstanding
solvation potential make them green solvents
but their toxicity needs to be understood
and controlled. Reliable toxicity prediction
can only be achieved through computational
means. Quantitative structure-property
relationships, known as QSPR, solve the
problem created by stringent environmental
regulations and costly and time consuming
experimental determination.
This EU International Incoming Fellowship
will see Professor Paul Popelier develop
ecotoxicological models for ILs in silico,
obeying OECD principles, based on available
toxicity data against various endpoints.
23
components for portable fuel cells that could
truly predictive QSPR models will be highly
be used to power consumer devices like
advantageous in designing the desired
mobile phones. Two of the key challenges
ILs. This project combines complementary
to adapting biological catalysts to replace
expertise in physicochemical parameters
inorganic ones are immobilising the enzymes
rooted in quantum chemistry and rigorous
to have the most efficient possible transport
chemometrics. Professor Popelier aims to
of reactants, products and electrons,
establish collaboration with experimental
and maximising the longevity of these
toxicologists at The University of Manchester
immobilised enzymes.
for experimental validation of the developed
models delivering innovative QSPR models
and expert systems for predicting toxicity of
ILs, ready for European regulatory purposes.
Dr Blanford and his group have discovered
numerous biomimetic surface modifications,
essentially using the enzyme’s natural
partners to orient the macromolecules for
efficient electron transport while preserving
Enzymes for energy conversion
their activity for months. As part of the
Fuel cells are electrochemical devices that
surface modification, they discovered a
directly convert chemical energy into
unique copper configuration that could be
electrical energy. These function like a
adapted to produce more efficient fuel-cell
battery but have the reactants like hydrogen
enzymes in common expression systems like
and oxygen fed from outside the cell.
E. coli.
These devices frequently rely on expensive
platinum-group metals to speed up the
energy conversion process. Some metalcontaining enzymes such as hydrogenases
and multicopper oxidases carry out the same
functions as efficiently as the precious metal
catalysts and use small amounts of abundant
elements such as iron, nickel and copper.
24
group’s research into rational electrode
The group also use an electrochemical quartz
crystal microbalance (EQCM) to test how realworld usage conditions affects the longevity
of fuel cell electrodes. While the enzymes
remain viable for days when a constant
output is required, rapidly varying the electric
current extracted from the electrodes could
diminish their lifetime to minutes. The group
Dr Christopher Blanford’s recent EPSRC
found that these destructive effects can be
fellowship work focused on exploiting
mitigated by limiting the electrode’s output
multicopper oxidases to create miniature
potential.
RESEARCH
SPOTLIGHTS
Considering the ever growing interest in ILs,
25
RESEARCH
Spotlight
CENTRE FOR
Synthetic
Biology
OF SUSTAINABLE CHEMICALS
AND NATURAL PRODUCTS
Industry stakeholders-partners
Our research
We have an established track record of
We have a strong portfolio of current research
pathway/biocatalyst control (e.g. orthogonal
leadership in industry and stakeholder
grants in the region of £42M and state-of-
regulatory circuits, riboswitches); chassis
collaborations in the chemicals/natural products
the-art-facilities underpinning our research
engineering (e.g. yeast, bacterial) for robust
sectors including:
in synthetic biology with world leading
and high yield industrial producers; informatics
programmes in biocatalysis (CoEBio3), systems
and genomics/metagenomics to facilitate
biology (MCISB) and protein redesign, structure
building block discovery; enzyme engineering
and mechanism (MCBC) as well as leading
and evolution to generate new biocatalytic
science technology programmes embedded in
module libraries; robotics for accelerated host
the wider MIB/UoM research portfolio. These
optimization and refactoring; metabolomics/
projects are already providing SynBio solutions
analytical science supporting chassis
to the green manufacture of fine chemicals,
optimization and intermediate/product analysis;
therapeutic small molecules and new routes to
pathway refactoring/assembly comprising
biofuels.
assembly of building locks/modules, pathways
prototypical pathways in engineered chassis;
ACIB, AstraZeneca, BASF, Bayer, Bruker, CatSci,
Charnwood Consulting, Codexis, Dr Reddy’s,
Evolva Biotech, GlaxoSmithKline, Janssen,
Orion, Lonza, Merck, Pfizer, Reaxa, Synthace,
Syngenta, Shell, Solvay, Unilever and more
EU science and training
programmes in synbio
The Centre of SYNBIOSCHEM integrates
In the wake of the human genome project, microbiology is currently undergoing a major
transition: we are now capable of obtaining a comprehensive molecular view of the entire
cellular circuitry of our microbes of interest, followed by an equally comprehensive reengineering of their cellular functions, called Synthetic Biology. Synthetic Biology aims at
the rational design of biological systems and living organisms using engineering principles,
to achieve new useful functions in a modular, reliable and predictable way. It has the
potential to drive a new industrial revolution in biotechnology, with applications in many
sectors, including healthcare, sustainable energy, green chemistry, pharmaceuticals, novel
materials and bioremediation. It requires cutting-edge research at the interface of biology,
engineering, chemistry and computing science. The Manchester Institute of Biotechnology
has assembled one of the strongest interdisciplinary teams with world-class expertise in all
these areas in a single state-of-the-art facility.
SynBio@MIB - Synthetic
Biology advancing synthetic
biotechnology
with a number of SMEs as well as large global
and industry in focused groups to explore
Rainer Breitling, Robin Curtis, Philip Day, Neil
Through active collaborations with a large
future perspectives in synthetic biology. In
Dixon, Sabine Flitsch, Roy Goodacre, Sam
variety of industry partners the Centre for
addition we have links with international
Hay, Finbarr Hayes, Douglas Kell, Ross King,
Synthetic Biology of Sustainable Chemicals and
Centres of Excellence including the Austrian
David Leys, Pedro Mendes, Jason Micklefield,
Natural Products (SYNBIOSCHEM) at the MIB
Centre for Industrial Biotechnology (ACIB),
Aline Miller, Clare Mills, Andrew Munro, Nigel
is harnessing the power of synthetic biology to
CSIRO biofuels cluster in Australia, SynBerc in
Scrutton, Eriko Takano, Nicholas Turner, Simon
propel chemicals/natural products production
the US (multi-university SynBio Centre), Beijing
Webb, Jim Warwicker, Lu Shin Wong.
towards ‘green’ and more sustainable
Genomics Institute and the Chinese Academy
manufacturing processes, and boost UK
of Sciences as well as several SynBio centres
research capacity by stimulating innovation
across Europe.
Associated researchers
Emerging societal, ethical, and regulatory
Andrew Balmer, School of Sociology
companies through regular Industry Days
26
We enjoy ‘hub status’ for major EU science and
expertise across several knowledge themes
training programmes in this sector, including
These technology platforms are integrated
including: biosynthesis pathway refactoring;
the innovative medicines initiative award CHEM
through iterative (n) cycles of (circuit design—
systems modelling and primary metabolic
21 (€25M), EU training networks (MAGIC,
computational modelling—experiment—data
pathway engineering, chassis (host) and end-
P4FIFTY) and EU FP7 consortium awards
analysis— modelling—redesign). These cycles
product yield optimization. These activities
(DIRECTFUEL; BIONEXGEN; AMBIOCAS;
will be implemented at different levels, within
are supported by cutting-edge Technology
BIOINTENSE; SUPRABIO). individual platforms as well as between
Platforms that are integrated to deliver
platforms, to establish a semi-automated and
outcomes in these knowledge themes and
integrated pipeline for the discovery and re-
ultimately assembled to deliver new sustainable
engineering of biocatalysts building blocks and
production prototypes for chemicals and
engineered pathways/cells.
Networks
BBSRC Natural Products Discovery and
natural product synthesis.
Bioengineering Network (NPRONET) led by
The technology platforms support integrated
Jason Micklefield (MIB, UoM) and Barrie
work programmes involving (but not
Wilkinson (John Innes Centre)
exclusively) the following discipline areas:
MIB-based synthetic biology
researchers
Pipeline to discovery
Technology Platforms
TP1 Rapid identification of components and accelerated directed evolution for SynBio
challenges associated with this rapidly
Sarah Chan, Faculty of Life Sciences TP2 Bioengineering technologies and Major EU funded projects in synthetic biology
advancing new technology are addressed
Phillip Shapira, MIIR
include BIONEXGEN, BIOINTENSE and BIOOX
in close interaction with social scientists
focused on developing the next generation of
and economists across The University of
We actively link across campus with network
TP3 Metabolomics, analytical science and biocatalysts for industrial chemical process.
Manchester.
partners as part of a wider synthetic biology
Strategic links in this field have been developed
and regulatory components.
hosted at the MIB bringing together academia
with industry and other key stakeholders in the
chemicals/natural products sectors.
computational and systems modelling of
strategy.
chassis design
metabolic engineering platforms
TP4 Computational systems biology, bioinformatics and genomics
27
Exploiting natural product assembly
line genomics and synthetic biology
for discovery and optimisation of
novel agrochemicals
Additionally, these co-expression technologies
a major global threat. New antibiotics are
quantity. In collaboration with Croda, a large
will be used to optimise a number of
urgently needed to combat the emerging
chemicals company with established routes
multivariate co-expression challenges, helping
critical problem of bacteria resistance. The
to market. The team will fully unlock the
to guide metabolic engineering efforts leading
European Centre for Disease Prevention and
potential of this promising broad-spectrum
to improved bioprocessing efficiencies, with
Control has estimated that antimicrobial
antibiotic using synthetic biology approaches.
Harnessing world leading expertise in natural
the potential to reduce both drug development
resistance costs the EU about 1.5 billion
product synthesis this project brings together
times and manufacturing costs.
euros in healthcare each year. The UK
Jason Micklefield, Professor of Chemical
Biology with Professors Greg Challis (Warwick),
Peter Leadlay (Cambridge) and Russell Cox
(Bristol) to develop a platform technology that
can exploit the potential of microbes for the
production of useful compounds for use in
agriculture and medicine.
Dr Dixon has also been awarded a Technology
Science Board (TSB) feasibility grant entitled
‘Rapid Engineering of Cellular Factories’
working alongside collaborators from UCL and
fighting antimicrobial resistance with a 5
year Antimicrobial Resistance Strategy Report
published in September 2013.
cluster refactoring will be used for optimum
expression and for introducing additional
diversity of the chemical structure. The
optimized biosynthetic machinery will then
to genetic intervention. In setting up SNIP the
Professor Roy Goodacre is bringing his
diagnostics) and small molecules (lantipeptides
expertise to bear on STREPSYNTH, an EU FP7
and indolocarbozoles) useful for multiple
funded project involving 16 partners and led by
industrial purposes (biopharmaceuticals,
Professor Anastassios Economou (Katholieke
additives, food technology, bioenergy).
Universiteit Leuven, Belgium).
consortium chose two classes of biomolecules
with obvious immediate industrial value and
application: heterologous proteins (industrial
enzymes, biopharmaceuticals, biofuel enzymes,
It is envisioned that SNIP is a modular platform
be introduced into Demuris’s optimised
STREPSYNTH aims to establish a Streptomyces-
that can be repurposed for diverse future
Synthace to advance the industrial application
Despite this, the majority of antimicrobial
production host for maximum yield required
based new industrial production platform
applications. Professor Goodacre is very excited
of synthetic biology. This is a collaborative
agents used today belong to old classes
for commercialisation. In addition, the methods
(SNIP) for high value added biomolecules.
to be involved in this novel synthetic biology.
R&D project, with the goal of demonstrating
of antibiotics discovered before 1970.
established in this work will be utilised for
Streptomyces lividans was chosen as a bacterial
His role is to develop a metabolomics and
Many microorganisms produce beneficial
the rapid creation of bacterial cellular factories,
In partnership with GSK, Professors
the activation of novel silent gene clusters
host cell because it has already shown itself to
fluxomics toolbox which aims to establish
compounds, such as penicillin made by a
for fine chemical production that is both
Jason Micklefield, David Leys and Eriko
identified from the genome sequence of
be highly efficient in extracellular production
standard operation procedures for robust
fungus with most microbes having the capacity
economically and environmentally sustainable,
Takano will investigate the biosynthesis
the broad-spectrum antibiotic producer and
of a number of heterologous molecules that
metabolomics and for 13C- and 15N-based
to produce many more compounds than
based on industrial biotechnology, and
and bioengineering of lipoglycopeptide
the products identified and characterised for
vary chemically, has a robust tradition of
fluxomics in Streptomyces lividans TK24.
are actually observed. If their full potential
advanced synthetic biology and bioprocesses.
antibiotics of the ramoplanin and
potential industrial applications.
industrial fermentation and is fully accessible
can be activated then it could provide new
enduracidin family. The lipoglycopeptides
compounds for the testing of medicines and
are highly potent antibiotics which have
agricultural chemicals.
This grant funds an ambitious programme
to rapidly sequence the genomes of 40
Engineered compartments for
monoterpenoid production using
synthetic biology
considerable clinical potential, with
ramoplanin having entered phase III clinical
trials. The team will develop alternative
China Partnering Award
microorganisms with the known ability to
biosynthetic engineering approaches to
Professors Eriko Takano and Nigel Scrutton
“Synthetic biology is an exciting new field with enormous potential to bring
TERPENOSOME is led by Professor Eriko
produce potential compounds that benefit
enable the rapid structural diversification of
have secured funding through a Synthetic
benefits to people around the world in all sorts of ways, for example producing
Takano, and together with Professor Nigel
agriculture. The team will work with partners
this class of antibiotics, providing access to
better antibiotics or manufacturing low carbon fuels. Co-funded initiatives such
Scrutton and partners across Europe, it will use
Biology China Partnering Award, co-funded
in the international agrochemical company
large numbers of lipoglycopeptide variants
by the Biotechnology and Biological Research
as this scheme will see British and Chinese scientists learning from each other’s
synthetic biology to engineer novel organelles
Syngenta to develop these as new herbicides,
with potentially improved antimicrobial
Council (BBSRC), the Chinese Academy of
expertise and benefiting from the globalisation of excellent science.”
for the overproduction of monoterpenoids
insecticides and fungicides, while partners at
activities, for subsequent development with
in microbial hosts. The project aims to
Sciences (CAS) and the Engineering and
the biotechnology company Biotica will focus
industrial partners.
generate a portfolio of generic methods for
Physical Sciences Research Council (EPSRC)
on compounds with use in human medicine.
the compartmentalization of biosynthetic
The new biosynthetic insights will be used
pathways for bioactive molecules; improve the
to guide the development of bioengineering
biosynthetic enzyme systems for more efficient
strategies aimed at altering the glycosylation,
bioprocessing and overproduce industrially
halogenation and lipidation patterns, as
relevant terpenoids, for commercialization by
well as the amino acid sequence of the
one of the partners.
lipoglycopeptides. The bioengineering
This £5M project is funded under the BBSRC
SLoLa initiative in partnership with Syngenta
and Biotica.
Development and application of
next generation synthetic biology Tools
Dr Dixon seeks to develop novel protein
production and metabolic engineering tools,
and demonstrate the applications of these
novel synthetic biology tools in the context
of the bioprocessing industry. Although
biopharmaceuticals offer many health
benefits along with substantial commercial
significant technical challenge. Dr Dixon will
funding is provided for up to four years and
it is anticipated that the partnerships will
lead to new joint grant applications and high
impact research.
Professors Eriko Takano and Nigel Scrutton
to engineer a wide range of derivatives for
methodology will be exploited by industrial
will collaborate with Professor Lixin Zhang at
other promising classes of antibiotics as
partner, Life Technologies, in synthetic biology
the Chinese Academy of Sciences Institute of
well as other natural product variants for
projects on a wide range of biotechnologically
Microbiology to establish cooperative research
alternative therapeutic and agrochemical
relevant high-value compounds. The second
on the use of synthetic biology approaches for
applications.
production of high-value fine chemicals.
the improved production strains for the widely
In a complementary project, funded by
used precursor material limonene, as well as
the TSB, Professor Eriko Takano aims to
the two high-value compounds that are the
use synthetic biology as a key technology
major target molecules of TERPENOSOME.
to discover and develop new antibiotics
“We at CAS attach great importance to international collaboration. The idea of
this programme is to put the best minds together. Together our scientists and
these from the UK can advance this field more efficiently. In the progress of their
cooperation, I hope they will further strengthen their linkages and collaboration,
and tackle bigger challenges for the needs of mankind.”
Cao Jinghua,
Deputy Director-General of Bureau of International Cooperation of CAS
overcoming common problems associated
with antibiotic discovery from natural
Delivering next generation
antibiotics
sources, such as poor understanding
technology, to allow multimeric protein
develop and demonstrate four important
relationships with Chinese scientists. The
methodologies developed here will be used
industry partner, ACS International, will exploit
Professor Douglas Kell, Chief Executive of BBSRC
to partner and develop long term fruitful
The generic compartmentalisation
opportunities, their production remains a
of the antibiotic producer, poor growth
“EPSRC is pleased to be part of this joint international call which demonstrates the
characteristics, reproducibility, poor yield
wide scope for synthetic biology to create impact in many academic fields. It has
One of the major challenges in healthcare is
and lengthy delays to market. Demuris Ltd,
the potential to create new solutions to address pressing global challenges, such
products to be produced more effectively,
the provision of new antimicrobial agents that
an SME with expertise in natural products
as the need for new fuels, better waste management and new medicines.”
along with the potential to provide a simpler
can combat antibiotic-resistant pathogens
discovery has identified a promising broad-
and more efficient manufacturing process.
(superbugs), which are widely recognised as
spectrum antibiotic but it is produced in low
flavours of a novel gene co-expression
28
government has made clear actions into
Bioinformatics and biosynthetic gene
STREPSYNTH: Rewiring the
Streptomyces cell factory for
cost-effective production of
biomolecules
Professor David Delpy, Chief Executive of EPSRC
29
RESEARCH
Spotlight
Systems
Biology
understanding the dynamics of biological systems
iGEM Team
(l-r): Marco Pinheiro, Jessica Birt; Matthew Birt; Elsa Axelsdottir; Ralf Wenz; Lorna Hepworth, Tim Curd; Divita Kulshrestha; Tan Vun
Hiang; Eriko Takano (Team Leader) and Rainer Breitling
MIB iGEM team take Best
Undergraduate Human
Practices Award at the World
Championships Jamboree
For the first time in history an undergraduate
team from The University of Manchester
competed in the International Genetically
Engineered Machine competition (iGEM),
the world’s premiere UG Synthetic Biology
competition. Student teams are given a
kit of biological parts at the beginning of
the summer from the Registry of Standard
Biological Parts. The teams use these parts
together with new parts of their own design
to build biological systems and operate them
in living cells.
After a century of studying nature in greater and greater detail, generating the “parts
list” of the molecular components within the cell, the biological sciences have undergone
a paradigm shift in the last decade, moving towards putting together these individual
molecular pieces to understand their interactions in a holistic context. Systems biology brings
together a wide range of information about cells, genes and proteins, as well as the small
molecules that act on and within these biological structures. In the service of its application
areas, such as drug discovery and industrial biotechnology, it gives a holistic perspective
aiming to track and eventually simulate the entire functioning of biological systems.
“We are very proud of what the team has
achieved – the Manchester iGEM team is
the only first-time undergraduate team
to win this award without the benefit of
Manchester Centre for Integrative
Systems Biology (MCISB)
building on the experience of earlier teams
Europe the Manchester iGEM team
from the same university. This makes
presented their project at the regional iGEM
their achievement all the more amazing.
The Manchester Centre for Integrative
Jamboree held in Lyon on 11 – 13 October
The team involves first-year to last-year
by standardisation bodies and database
Systems Biology (MCISB) at The University
2013 gaining gold medal status and Best
students working very closely together”.
providers, and effectively allow the molecular
ChEBI provides for the bioscientific
of Manchester was founded in 2006
parts list to be catalogued. In addition to this,
community semantic, biological
having been awarded £6.4M by the BBSRC
further relevant information such as names,
and chemical information as
and EPSRC to pioneer the development
chemical formulae, structures, relationships and
well as stable identifiers for small
of new experimental and computational
properties are also associated with the various
chemical compounds relevant in
technologies in Systems Biology, and their
entities in the databases, providing resources
biology enabling the integration of
exploitation.
that are useable by both software tools and
metabolomics and systems biology.
Undergraduate Human Practices Award
which they went on to win at the World
Championship Jamboree in Boston.
Professor Eriko Takano
Team Leader iGEM
by the MCISB, members of the centre are
now applying these techniques to a range of
applications, from biotechnology through to
systems medicine.
of antibiotic production, awakening “sleeping” antibiotic biosynthesis gene clusters discovered in newly sequenced
microbial genomes. This approach will aid in the combat against antibiotic resistant bacteria, which is an emerging
public health threat worldwide. They will also be applying the synthetic biology tools developed in the group to design
and produce not only antibiotics, but a wide range of bioactive molecules, including anticancer agents. Using and
redesigning the enzymes and microbes found in nature they aim at expanding chemical diversity and biotechnological
efficiency, while avoiding the negative environmental impact of classical organic chemistry at the industrial scale. This
synthetic biology approach brings together expertise from molecular microbiology and many other disciplines, reaching
out towards chemistry, computing science, and engineering. In contrast, the Breitling group explores the application of
bioinformatics and systems biology techniques to the engineering of “designer microbes”, and using metabolomics and
transcriptomics in the diagnosis and debugging of the organisms created by synthetic biology approaches.
researchers themselves. The database Chemical
Entities of Biological Interest (ChEBI) acts as
a resource for such information and provides
stable identifiers in the area of small molecules
of biological interest.
Professor Pedro Mendes, together with Dr
2012-13 saw the expansion of our research strengths in SynBio with the arrival of Professors Eriko Takano and Rainer
Breitling. The Takano group is focused on the use of synthetic biology for the large-scale genome-based re-engineering
These identifiers are assigned to entities
such as genes, proteins or small molecules
Expanding upon the approaches developed
30
system require stable and unique identifiers.
Along with 60 other teams from across
Chris Steinbeck from the EMBL - European
Chemical Entities of Biological
Interest (ChEBI)
In order to build up holistic models from such
a vast collection of diverse data, integration
of individual units of information from many
diverse databases needs to be performed. This
integration of such a high volume of data can
only feasibly be performed computationally.
To facilitate smooth integration, individual
molecular components within the cellular
Bioinformatics Institute at EMBL and Dr Neil
Swainston of MCISB will further develop
the ChEBI resource and create surrounding
tools towards comprehensively addressing
the chemical informatics (software and data)
needs of the systems biology and metabolic
modelling communities, enabling them to
create comprehensive and reusable models
to facilitate whole-systems research into
pressing public health and energy challenges.
COPASI (COmplex PAthway
Simulator)
Bioscience research is becoming increasingly
dependent on construction and simulation
of computational models as the technical
aspects of modelling and simulation are
often overwhelming to a large number of
biomedical researchers. COPASI provides the
appropriate numerical algorithms shielded
by a user interface to assist the researcher
in conducting the required simulations. This
project aims to extend the capabilities of
COPASI by adding the means to simulate
31
SYBIL provides insight into
skeletal diseases
Perfecting drug combinations
to combat severe diseases and
conditions
models with explicit time delays; providing a
“This research is the second, important
mechanism for easy calculation of summaries
stage of our understanding of the human
of entire simulations and groups of
genome. If the sequencing of the human
simulations and incorporating a new feature
genome provided us with a list of the
SYBIL (Systems biology for the functional
that will allow researchers, for the first time,
biological parts then our study explains
validation of genetic determinants of skeletal
A multidisciplinary team of researchers, led
to be able to navigate the entire history of
how these parts operate within different
diseases) is a large scale collaborative project
by Professor Douglas Kell, have found a
However, using ideal drug combinations
a model, such that the reasons for changes
individuals. It provides a network mapping
that brings together a complementary group
way of identifying ideal drug combinations
the researchers suggest they can block
that took place are formally identified, as
all the small molecule transactions that
of world-class scientists, disease modellers,
from billions of others which would prevent
inflammation and therefore greatly reduce
well as decisions on the model structure.
define what goes on with these so-called
information technologists and industrialists.
inflammation from occurring. The findings,
the damage caused by non-communicable
The project will also improve and extend
metabolites in human biochemistry. The
The overall concept of this project is to
published in Nature Chemical Biology, could
diseases such as stroke. Although the
Another advantage of choosing ideal drug
the software’s interoperability and standards
results provide a framework that will
functionally validate genetic determinants
be the first step in the development of new
researchers have initially concentrated
combinations is that it allows patients to
compliance to allow bioscience researchers
lead to a better understanding of how
of common and rare skeletal diseases to
drug combinations to combat severe diseases
on stroke, they believe the process can
take smaller doses, which reduces potential
to freely exchange data and models.
an individual’s lifestyle, such as diet, or a
gain a mechanistic understanding of disease
and conditions.
be applied to all drugs and for a huge
toxicology concerns.
particular drug they may require is likely
processes and age-related changes, and
to affect them according to their specific
to deliver new and validated therapeutic
Most non-infectious disease, such as cancer,
an evolutionary computer program which
genetic characteristics. The model takes us
targets.
stroke and Alzheimer’s are worsened by
rapidly sifted through nine billion different
inflammation, which is the body’s natural
combinations of potential drugs.
COPASI (COmplex PAthway Simulator) is
based on the GEPASI simulation software
(General Pathway Simulator) that was
an important step closer to what is termed
defence mechanism. Inflammation has
diverse and complex group of diseases that
evolved to help fight infection but can also
primarily affect the development skeleton.
be very damaging in long term disease,
There are more than 450 unique and well-
prolonging suffering and ultimately risking
Douglas Kell, Professor of Bioanalytical
characterised phenotypes that range in
premature death. After a stroke, the body
Science at the MIB said: “To understand
severity from relatively mild to severe and
reacts to the injury as if it were an infection,
development of COPASI was funded by
the behaviour of a system one must have
lethal forms. Although individually rare, as a
causing further damage. By blocking the
the Virginia Bioinformatics Institute, the
a model of it. By converting our biological
group of related orphan diseases, RSDs have
inflammation, the chances of survival or
Klaus Tschira Foundation, the BBSRC and
knowledge into a mathematical model
an overall prevalence of at least 1 per 4,000
higher quality of life following a stroke are
format, this work provides a freely accessible
children, which extrapolates to a minimum of
thus greatly enhanced. This can be achieved
additional follow on funding from the BBSRC
tool that will offer an in-depth understanding
225,000 people in the 27 member states and
by quickly and effectively identifying
to maintain and develop this important
of human metabolism and its key role
candidate countries of the EU.
combinations of drugs which can be used
resource.
in many major human diseases. It offers
Pedro Mendes. It is the result of an
international collaboration between The
University of Manchester (UK), the University
of Heidelberg (Germany), and the Virginia
Bioinformatics Institute (USA). The initial
EPSRC. Professor Pedro Mendes has received
‘personalised medicine’, where treatments
are tailored according to the patient’s genetic
information.”
the most complete model of the human
metabolic network available to date to
Study maps human metabolism
in health and disease
help analyse and test predictions about the
physiological and biochemical properties
of human cells. Pharmaceutical drugs get
Scientists from the MIB working with
into cells by ‘hitchhiking’ on the transporter
researchers from Cambridge, Edinburgh,
proteins that normally serve to move small
Berlin, Reykjavik and San Diego among
molecules around. An area of particular
others have produced an instruction manual
interest is thus the incorporation into our
for the human genome that provides
metabolic network map of knowledge of
a framework to better understand the
pharmaceutical drug transport.”
relationship between an individual’s genetic
Dr Jean-Marc Schwartz will lead one of the
Sorting and testing 50 drug combinations
are having a stroke – and even then do not
at a time using robotics in the laboratory,
completely solve the problem, often leaving
the scientists were able to find effective
sufferers with serious disabilities.
combinations and then refine them as
work packages and, alongside Professor
Existing ‘clot-busting’ stroke drugs are only
Roy Goodacre, provide the core qualitative
effective if administered within three hours
systems biology analyses for the consortium.
after the stroke – often very difficult to
applied to spectroscopic, mass spectrometric
and metabolomic data and over 11 years in
Erythrocyte and fibrin imaging for
disease diagnosis
vibrational spectroscopy. He has published
over 180 peer-reviewed papers and has
co-edited books on metabolic profiling and
systems biology. He is the Editor-in-chief
In a separate study, Professor Douglas Kell has
shown that unliganded iron is responsible for a
mapped 65 different human cell types and
Institute in Cambridge (UK), said:
editorial board of the Journal of Analytical
large number of degenerative and inflammatory
model yet to explain why individuals react
differently to environmental factors such
as diet or medication. Pedro Mendes,
Professor of Computational Systems Biology
commented:
for treating inflammation.
spectrometry (MS), advanced data analysis
of the journal Metabolomics and on the
model, providing the most comprehensive
lead to the development of tailored therapies
Roy has over 18 years experience in mass
Dr Nicolas Le Novère, from the Babraham
drug targets in order to produce the network
combinations. Ultimately, they hope this will
together.
make-up and their lifestyle. The team have
half of the 2,600 enzymes that are known
many times as necessary to find ideal
variety of diseases. The team developed
Rare skeletal diseases (RSDs) are an extremely
developed in the early 1990s by Professor
achieve as people are often unaware they
and Applied Physics. Finally, he is a founding
diseases. In collaboration with Prof Resia Pretorius
“This is a model that links the smallest
director of the Metabolomics Society and
(University of Pretoria, South Africa), he has now
molecular scale to the full cellular level. It
director of the Metabolic Profiling Forum.
shown that this manifests in highly aberrant
contains more than 8,000 molecular species
morphologies of fibrin - the protein responsible
and 7,000 chemical reactions – no single
for blood clotting - and or red blood cells. Work
researcher could have built this alone. Having
is in progress to use these kinds of measurements
large collaborations like these, using open
for the rapid, cheap, and minimally invasive
standards and data-sharing resources, is
diagnosis of the severity of such diseases and the
crucial for systems biology.”
effectiveness of their treatment.
Aberrant morphologies of red blood cells in the genetic disorder hereditary haemochromatosis
Picture courtesy Prof E. Pretorius
32
33
Europe PubMed Central
RESEARCH
Spotlight
Text
Mining
facilitating the discovery, extraction and
structure of knowledge
Manchester (Ananiadou, McNaught), NICE
and the University of Liverpool will address
PubMed Central repository, in collaboration
these limitations by exploring new research
with the National Institutes of Health (NIH) in
methods, which combine text mining and
Funded by the Medical Research Council
the United States. NaCTeM collaborates with
machine learning to produce novel search
(MRC) this project will address current
the European Bioinformatics Institute (EBI),
while screening tools for public health
limitations in Evidence-based public health
MIMAS and the British Library. NaCTeM’s
reviews. Text mining methods will discover
(EBPH) interventions by exploring new
contribution to this major project is in the
automatically knowledge from unstructured
research methods which combine text
provision of advanced semantic search
data and machine learning will support the
mining and machine learning to produce
over full papers, involving massive analysis
prioritisation and ranking of the extracted
novel “search while screening” tools for
at the level of individual facts (some 83m
information into meaningful topics. The
public health. This is a collaborative project
sentences have been analysed so far for our
combination of text mining and machine
with NICE and the University of Liverpool.
EvidenceFinder application).
learning methods will reduce the burden of
annotated documents, such as concepts,
e.g. anatomical entities, genes, chemical
compounds, links to databases, and relations
amongst concepts, through a sophisticated
search facility. EvidenceFinder presents the
query, where these questions are derived
from the abovementioned analysed and
answers. For example, given the query “IL2”, EvidenceFinder will present questions
such as “What inhibits IL-2 receptor?”,
“What binds to IL-2 receptor?”, etc., for the
This project was led by Professor Sophia
user to click on. This allows information to
Ananiadou in collaboration with Professor
be located that might otherwise be missed,
maintenance is a manual and expensive
Jun’ichi Tsujii, Professor Douglas Kell, and
and to quickly establish which articles do and
curation process due to new discoveries.
Professor Hiroaki Kitano (Systems Biology
do not contain information being sought.
EUPMC funders led by Wellcome Trust.
The National Centre for Text
Mining (NaCTeM) provides
text mining systems and
infrastructure at large scale
However, PathText links pathway models with
Institute, Japan). It was funded by BBSRC.
NaCTeM has developed text mining tools,
textual evidence by combining and ranking
Event extraction in collaboration with
resources and services to support the
relevant information from the literature using
AstraZeneca.
automatic extraction of information and
text mining methods.
http://www.nactem.ac.uk/pathtext2/
knowledge from the growing amount of
literature in an efficient, manageable and
comprehensive manner at large scale.
Applications areas include: drug discovery,
chemistry, systems biology, clinical trials,
public health, medical historical archives,
newswire analysis, pathway reconstruction
and advanced search systems. NaCTeM, led
by Professor Sophia Ananiadou and Dr John
McNaught, is a fully sustainable text mining
centre. It has been funded by JISC, BBSRC,
MRC, AHRC, Wellcome Trust, NIH and
industrial partners.
means, Pathway model reconstruction and
PathText integrates and ranks the evidence
To understand complex biological
systems in detail we need to incorporate
knowledge scattered over millions of
34
be completed more quickly, thus meeting
policy and practice timescales and increasing
their cost efficiency. They also allow more
timely and reliable reviews, thus improving
decision making across the health sector.
Text mining supporting public
health
and annotation are supported by Argo, a
very large, long-running digital sources, the
Web application for analysing (primarily
British Medical Journal (BMJ) (1840 - present)
annotating) textual data. The workbench
and the London-area Medical Officer of
supports the combination of elementary
Health (MOH) reports (1848-1972), by
text-processing components developed by
applying text mining techniques to enrich
the centre to form comprehensive processing
these data with semantic annotations. The
workflows. It provides functionality to
project plans to extend its impact to the
manually intervene in the otherwise
following sectors: public health, public policy,
automatic process of annotation by
publishing, media and libraries, with a view
correcting or creating new annotations, and
to ensuring sustainability and wider uptake
facilitates user collaboration by providing
of methods and technologies.
practice and guidance. Their development
currently hosts over 100 text-processing
currently involves first searching, then
components.
automatically. NaCTeM’s interoperable text
NaCTeM’s text mining tools were recently
screening and synthesizing evidence from the
mining infrastructure links the text analysis
ranked highest in three separate tasks to
vast amount of literature. Unlike systematic
Argo benefits users such as text analysts by
providing an integrated environment for
develop software that can identify important
reviews, EBPH reviews require dynamic
with an annotation environment to further
information in chemical text. In particular,
and multidimensional views of relevant
the development of processing workflows;
support curators in their task.
NaCTeM was ranked first out of 12 groups
information from the literature, without
annotators/curators by providing manual
in the recognition of chemicals, and the
relying on a priori research questions.
annotation functionalities supported
NaCTeM’s text mining services FACTA+
between concepts and bioprocesses), KLEIO
recognition of genes, and first out of 23
teams in a task involving the recognition of
chemical names.
by automatic pre-processing and postAs a result, EBPH reviewing is a time
processing; and developers by providing a
consuming and resource intensive process
workbench for testing and evaluating their
that can take more than a year to complete.
automatic text analytics.
(advanced semantic facetted search based
BioCreative IV is the latest in a series of text
Since crucial information can be difficult
on bio-entities) and MEDIE (semantic search
mining challenges in which teams from both
to locate, and indeed understand given
These platforms have been funded by the EC in
based on bioprocesses). Novel methods such
academia and industry apply their technology
the complex nature of EBPH problems, the
the framework of META-NET and by the BBSRC.
as automatic event and biological process
to extract a range of types of information
multiple causes and interrelations between
http://argo.nactem.ac.uk
recognition from texts have facilitated this
from text.
interventions, diseases, populations and
http://nactem.ac.uk/ucompare/
task.
outcomes can remain hidden.
of Manchester, seeks to demonstrate the
potential of text mining in medical history.
sharing capabilities for user-owned resources.
standalone application (U-Compare) that
PathText currently links CellDesigner with
for Text Mining (NaCTeM) and the Centre
Initially an asset will be created out of two
The workbench builds upon a previous,
components and text mining workflows
collaboration between the National Centre
Interoperability, text mining processing,
play a central role in public health policy,
in their semantic context, from text
Council (AHRC) this cross-disciplinary
and Medicine (CHSTM) at The University
tools and services including the identification
of reactions, genes, proteins and metabolites
Funded by the Arts and Humanities Research
Text mining interoperable
software platforms
Evidence-based public health (EBPH) reviews
NaCTeM receives three first place
rankings at Biocreative IV
Mining the history of medicine
for the History of Science, Technology
from text using a number of text mining
(mining direct and indirect associations
PathText: reconstructing
pathways with evidence from
text
http://www.nactem.ac.uk/facta/
producing public health reviews which will
user with a list of questions relating to his
indexed facts, thus are known to have
scientific publications. Using conventional
Supporting evidence-based
public health interventions using
text mining
Europe PMC forms a European version of the
The objectives are to deliver content from
Text mining software facilitates the discovery, extraction and structuring of relevant
knowledge from unstructured text. The output of text mining systems can enrich
documents with semantic information, which can in turn be used to develop search
systems that allow users to locate information of interest more quickly and efficiently
than is possible using traditional search methods.
An MRC funded project between
Open Source Software receives
funding boost
This EU FP7 funded project will see NaCTeM
working with 8 partners across Europe on
OSSMETER which aims to extend the field
of automated analysis and measurement
of Open Source Software, and develop a
platform that will support decision makers
in the process of discovering, comparing,
assessing and monitoring the health, quality,
impact and activity of open-source software.
To achieve this, OSSMETER will compute
trustworthy quality indicators by performing
advanced analysis and integration of
information from diverse sources including
the project metadata, source code
repositories, communication channels
and bug tracking systems of Open Source
35
Tackling early cognitive decline –
a text mining perspective
Software projects. OSSMETER does not aim
at building another OSS forge but instead
at providing a meta-platform for analysing
existing Open Source Software projects
Critically only 50% of people with dementia
that are developed in existing Open Source
ever receive a diagnosis that could lead to
Software forges and foundations such as
them receiving medical care and support.
SourceForge, Google Code, GitHub, Eclipse,
Professor John Keane is collaborating with
Mozilla and Apache.
Professor Alistair Burns and Dr Iracema Leroi
RESEARCH
Spotlight
from FMHS as part of a joint programme,
NaCTeM leads work package 4, which
with Lancaster University and King’s College,
concerns the extraction of quality metrics
London to look at novel ways in which
related to the communication channels,
data and text-mining techniques, combined
and bug tracking facilities of Open Source
Software projects using Natural Language
Processing and text mining techniques.
NaCTeM will utilise supervised text mining
techniques to automatically identify
defining the past, informing the present, driving our future
with adaptive user interfaces, may enable
Linked2Safety : advancing
clinical practice and data security
in clinical research
sufferers’ new opportunities for self-referral.
Funded by the EPSRC, the project is entitled
SAMS: Software Architecture for Mental
Health Self-Management.
questions and answers in threads and
Electronic Health Records (EHRs) contain an
analyse types of threads (e.g. problems,
increasing wealth of medical information.
By exploiting novel data and text mining
solutions, complaints) based on the extracted
They have the potential to support clinical
techniques, combined with adaptive user
questions and answers in threads. Opinion
and medical research, improve health
interfaces, SAMS will validate thresholds
mining techniques will be adopted, for the
policies, ensure and empower patients’
by non-intrusively examining changes in
classification of sentiment, in threads will
safety and improve the overall quality of
performance in people with established
be based on a combination of supervised
healthcare. The Linked2Safety project is
cognitive dysfunction and mild Alzheimer’s
methods using statistical, linguistic and
funded through the EU 7th Framework
disease and begin to explore the potential
pragmatic features, and resources such as
Programme and involves ten partners from
for technology-enhanced detection of early
Wordnet and Wiktionary. Text mining analysis
eight EU countries including MIB researchers
cognitive dysfunction. Patterns of computer
of online threads at several levels will result
Professor John Keane and Dr. Goran Nenadic
use and content analysis of e-mails, such as
in rich multi-layer, feature-based annotations
together with colleagues from the School of
forgetting topics, expressions of concern,
over the input texts, enabling indexing,
Computer Science.
emotion, etc., will be analysed and coupled
Understanding how life works and using this knowledge to our advantage is the basis of our
success as an intelligent species. A sustainable society is achieved through advances in basic
knowledge and technology. The science of biology is evolving at an unprecedented pace.
Biological systems are quantitative and heterogeneous and these realisations have far reaching
consequences for their measurement and modelling. This involves expanding our traditional
understanding of the single organism to the molecular basis of life as well as the workings of
the entire biosphere. In order to achieve this we are developing powerful novel technologies
based on mass spectrometry and spectroscopy that provide detailed chemical information on
the cellular make up of cells and can do this both as a function of time and space.
to feedback mechanisms to enhance users’
flexible interrogation, manipulation and
re-use in subsequent OSSMETER processes.
The project aims to advance clinical practice
cognitive self-awareness, enabling them
OSSMETER website: http://ossmeter.eu and accelerate medical research by providing
to self-refer themselves for expert medical
healthcare professionals, pharmaceutical
advice.
companies and patients with a secure
Mass Spectrometry@MIB
and peptides at the molecular level and
Barran formed a team with Professors
have developed IM-MS (ion mobility-MS)
Ted Hupp and Kathryn Ball (Edinburgh/
Gas-phase ion chemistry research provides
instrumentation, in collaboration with
CRUK) and Dr Penka Nicolova (KCL) to
an enhanced understanding of the analytical
Waters, to investigate changes in protein
investigate the flexibility of the protein p53
framework facilitating the efficient and
This project is supported by the EPSRC,
techniques that underpin proteomics,
Dementias Neurodegen Network (DeNDRoN),
conformation to understand biological
using mass spectrometry and IM-MS. This
homogenized access to shared distributed
metabolomics and the investigation of
work has been extended to examine other
Electronic Health Records (EHRs).
The Alzheimer’s Society, Microsoft Research,
systems using MS-based techniques which
other molecules of biological significance.
the University of British Columbia and Johns
have widespread application. The Barran
intrinsically disordered proteins of the Cancer
New developments in quantitative mass
Hopkins University School of Medicine.
group is currently developing two new ion
Genome, including c-MYC, and MDM2 and
spectrometry provide much needed
clinical research to support early detection of
mobility instruments, one to provide higher
has attracted further collaborations with
information for modelling of biological
potential patient safety issues based on the
resolution cross section measurements and
Professor Richard Kriwacki (Tennessee) and
networks, while techniques are being
genetic data analysis and the extraction of
one to also allow for photo-interaction.
Professors Giovana Zinzalla and Gunner
developed for the analysis and quantification
the bio-markers associated with an identified
of a variety of post-translational
An extremely successful area of multidisciplinary
type of an adverse event. It also aims to
modifications.
investigation is the structure activity relationship
Linked2Safety facilitates the use of EHRs in
support sound decision making and effective
organization and execution of clinical trials.
of a group of anti-microbial peptides known as
In September 2013 we were delighted to
welcome Professor Perdita Barran to the
36
Technologies
β-defensins, where Barran led a platform grant
(EPSRC) funded team comprising 7 academic
The underlying architecture will be based on
MIB as Chair of Mass Spectrometry and
a common shared semantic infrastructure
groups. Research in this area continues to be
Director of the Michael Barber Centre for
including linked data, ontologies, common
fruitful, and has recently been extended to
Collaborative Mass Spectrometry. The Barran
medical vocabularies and state-of-the-art
examine other chemokines in collaboration with
group have developed and maintained
clinical data analytics techniques.
Professor Brian Volkman (Wisconsin, USA) and
many successful collaborations within
chemokine GAG interactions with Professor
academia and industry in developing and
Rob Woods (Georgia USA). Barran is currently
applying gas phase methods to problems of
collaborating with Professor Cait MacPhee
biological and medical relevance. Through
and Dr Tilo Kunath (Edinburgh) and Professor
the adoption of solvent free methodologies
David Allsopp (Lancaster) to look at pre-fibrular
they are able to provide an understanding of
amyloid aggregates of neurodegenerative
structure function relationships of proteins
proteins.
Larson (Karolinska Institute). They have
other on-going collaborations with groups
in UCL, Bristol and Birmingham, Innsbruk
and EPL (Switzerland). Since building their
IM-MS instrument they have also been
sought by several groups in the UK as well
as in the USA and Brazil, to provide accurate
calibration for their mobility data obtained
with commercial IM-MS instruments.
37
Professor Perdita Barran joins MIB
Perdita graduated from The University of Manchester with a degree in Chemistry with
Industrial Experience in 1994. She went on to obtain a PhD in Chemical Physics in 1998
from Sussex University under the supervision of Professors Tony Stace and Sir Harry Kroto.
Following postdoctoral appointments in the UK and USA she was awarded an EPSRC
Advanced Research Fellowship to study “The Structure and Energetics of Peptides and Small
Proteins” which she took up at the University of Edinburgh where she helped to establish a
Centre of Proteomics (SIRCAMS).
Since 2009 she has published 38 papers with five currently in review. She has a total
publication list of 70 peer reviewed papers (over 900 citations, H factor 23). This impressive
The High Arctic camel on Ellesmere Island during the Pliocene warm period, about three-and-a-half million years ago. The camels lived in a boreal-type
output spans work on the fundamentals of Ion Mobility Mass Spectrometry, including
forest. The habitat includes larch trees and the depiction is based on records of plant fossils found at nearby fossil deposits.
instrument development all the way to its application to biomedical problems. Barran
CREDIT: Dr. Julius T. Csotonyi, scientific illustrator (csotonyi.com)
has communicated 2 book Chapters, and an entry for the European Encyclopaedia of
Biophysics (2012). Perdita was awarded The Desty Memorial Prize for ‘Innovation in
Professor Perdita Barran
Separation Science in 2005, and the Joseph Black award from the Royal Society of Chemistry
Chair of Mass Spectrometry and
2009 for her ‘significant developments in the fields of mass spectrometry and separation
Director of the Michael Barber
science, especially ion mobility techniques’ Recently she was appointed as an Editor of the
Centre for Collaborative Mass
International Journal of Mass Spectroscopy.
Spectrometry.
ZooMS - short for ZooArchaeology by
Palaeobiodiversity and
vertebrate evolution
Mass Spectrometry – is a pioneering new
Recently, Dr Mike Buckley was approached by Dr
technique called “collagen fingerprinting”
Natalia Rybczynski, a vertebrate paleontologist
which uses the persistence and slow
with the Canadian Museum of Nature to
evolution of collagen as a molecular
identify bone fragments dating from three-
barcode to read the identity of bones. The
and-a-half million years ago. By extracting
method, developed by Dr Mike Buckley
minute amounts of collagen, the dominant
“This is the first time that collagen has
been extracted and used to identify
a species from such ancient bone
fragments. The fact the protein was able
to survive for three and a half million
years is due to the frozen nature of
Adopting a combined
experimental-computational
approach
approaches to studying carbohydrate
during his PhD, uses a well-established
structure.
protein found in bone, from the fossils and
approach, peptide mass fingerprinting,
using chemical markers for the peptides that
allied to high throughput Time of Flight
make up the collagen, a collagen profile for the
Many advances in medicine, biology,
and Computation has joined forces with Dr
Mass Spectrometry. Bones are identified by
fossil bones was developed. Dr Buckley then
chemistry and materials science of the last
Ewan Blanch, Reader in Biophysics and a
differences in the mass of the peptides which
compared the profile to 37 modern mammal
few decades owes much to the structural
Raman spectroscopist on an EPSRC funded
arise as a result of sequence differences
species, as well as that of a fossil camel found in
information that has been obtained
project to develop a combined computer
between species.
the Yukon. The collagen information, combined
Dr Mike Buckley
for proteins and nucleic acids by X-ray
modelling and spectroscopic lab-based
with the anatomical data, demonstrated that
Royal Society University Research Fellow
crystallography and NMR spectroscopy, and
approach to characterising the structures
Secondary Ion Mass
Spectrometry (SIMS)
which has revolutionised our view of how
of carbohydrates, from simple sugars to
life works. Unfortunately, these techniques
key carbohydrate polymers known to be
are far more difficult to apply to the main
involved in regulating biological functions
SIMS is developed and used for the analysis
class of biomolecules - carbohydrates.
generating a uniquely incisive new tool for
and imaging of chemical and biological
Despite carbohydrates constituting over half
glycobiology. The team will be combining
systems, including advanced materials,
of the biomass of our planet and performing
high level quantum chemistry calculations,
an almost limitless number of roles in living
molecular dynamics simulations and highly
systems, we don’t really understand how
detailed Raman spectra to develop and
they work in the same way that we do for
validate novel computer modelling tools
proteins and DNA. The lack of definitive
that will provide new insights into many
The study of ancient DNA enables the
data means there is still considerable debate
other areas of research, such as protein-
prevalence of diseases in past populations to
M. tuberculosis is the second deadliest
as to how we even define structure in
ligand interactions and DNA-drug molecule
be determined by analysis of skeletons for
infectious agent worldwide, yet little is
carbohydrate polymers. In order to best
binding.
the presence of pathogen DNA. In a recent
known about the bacterium’s historic genetic
study of Mycobacterium tuberculosis (MTB)
variations and how such historic strains
published in PNAS, Terry Brown, Professor
have evolved over time. The genotyping
of Biomolecular Archeology, together with
of historic strains of M. tuberculosis could
researchers from York and Durham, have
enable comparisons between strains from
obtained the detailed genotype of a historic
different geographic locations and time
strain of M. tuberculosis from a female
periods, and may yield clues about the
single cells and biological tissue. The aims
involve novel insights into the chemical and
spatial organisation and function of these
systems at the molecular level.
Nick Lockyer and Professor John Vickerman
are developing applications of SIMS in
areas involving the characterisation and
classification of cells and tissue at the
molecular level. They are also working
closely with industry to develop new
instrumentation and analytical protocols to
advance SIMS applications in biosciences.
38
Forensics and archaeology
capitalise on the immense potential of
carbohydrates in both science and industry
we have to understand in more detail
the molecular principles that govern their
assembly, organisation and interactions with
other molecules which requires alternative
Paul Popelier, Professor of Chemical Theory
Although the resulting development of
new computational tools will be focused
on the structures and behaviour of
carbohydrates, the end product will also be
widely applicable to all other biomolecules,
particularly proteins and nucleic acids.
the Arctic. This has been an exciting
project to work on and unlocks the huge
potential collagen fingerprinting has to
better identify extinct species from our
preciously finite supply of fossil material.”
the bone fragments belonged to a giant camel
as the bone is roughly 30% larger than the
same bone in a living camel species.
Discovery of detailed genotype
of a historic strain of M.
tuberculosis
adolescent buried sometime between 1840
are particularly interested in linking strain
and 1911 in a crypt in Leeds, England
variations to changes in TB virulence during
through the use of pioneering new methods
the medieval period, when Britain became
based on next generation sequencing.
increasingly urbanised. They are also
pathogen’s evolutionary history. The group
comparing strain data for TB in Europe with
similar results from the Americas, the latter
helping us to understand why many native
Americans died of TB after first contact with
Europeans even though strains of TB had
been endemic in the New World for many
years prior to contact. The Brown group
have worked on several diseases, including
malaria and syphilis, and most recently on
tuberculosis and leprosy.
39
Terry Brown, Professor of Biomolecular Archaeology
I became fascinated with the natural world when I was very young. I began my research
career studying the effects of metal pollution on microorganisms and the tolerance that
some plants display to high concentrations of toxic metals. I then became excited by
DNA and worked on mitochondrial genes in fungi in order to learn the new (in those
days) techniques for gene cloning and DNA sequencing. I contributed to the discovery of
mitochondrial Group 1 introns and to work that described the base-paired structure of
these introns. I then became interested in ancient DNA and was one of the first people
internationally to carry out DNA extractions with bones and preserved plant remains.
This work has required close collaboration with archaeologists, both in Manchester
and elsewhere, and has led to my current interests in the origins of agriculture, genetic
profiling of archaeological skeletons, and the evolution of disease.
“This project will provide
a new dimension to our
understanding of early
European agriculture
and also inform work on
the impact that future
environmental change
could have on the
sustainability of modern
cereal cultivation.”
Raman spectroscopy and cells:
lighting up sub-cellular research
Fingerprinting food
Raman spectroscopy is a physicochemical
chemometric approaches have found new
method based on the interaction of light
applications as a fast and accurate viable
with matter. In Raman scattering a molecular
bacterial detection and quantification
vibration yields light of a different wavelength.
method for routine use in the milk and
This enables a very powerful and non-invasive
meat industry. Major food adulteration and
analysis of the chemical and structural
contamination events seem to occur with
information of a sample; indeed one can
some regularity, such as the widely publicised
use this to measure protein structure and
adulteration of milk products with melamine
posttranslational modifications. Moreover,
and the recent microbial contamination of
it is highly sensitive and when coupled with
vegetables across Europe for example; and
atomic force microscopy (AFM) has exquisite
more recently the horsemeat scandal, which
Nuclear Magnetic Resonance (NMR)
spatial resolution (<20 nm). In the MIB we
has rocked consumer confidence in the
spectroscopy is an essential platform
are developing Raman to analyse cells and
food supply chain. With globalisation and
technology for research in the life and
their components and this has recently been
rapid distribution systems, these can have
chemical sciences and currently makes a major
facilitated via three new approaches: (i) optical
international impacts with far-reaching and
contribution to UK research priorities such as
trapping of eukaryotic cells using Raman
sometimes lethal consequences. These events,
ageing and infectious disease characterizing
tweezers; (ii) coupling in situ cell growth
though potentially global in the modern
biomolecular structure, function and dynamics.
facilities within the instrument so that drugs
era, are in fact far from contemporary, and
Our capabilities in NMR have expanded rapidly
and metabolites can be mapped within cells;
deliberate adulteration of food products is
with the purchase of an 800 MHz instrument
(iii) the very recent acquisition of an AFM-
probably as old as the food processing and
from Bruker. This addition to our facility, which
Raman system which shall be developed for
production systems themselves. Professor
currently houses 400 MHz, 500 MHz and 600
tip enhanced Raman spectroscopy (TERS)
Roy Goodacre’s critical review “Fingerprinting
MHz instruments, will open up a substantial
imaging, following on from our pioneering
food: current technologies for the detection
number of new research programmes focusing
work in bacterial surface enhanced Raman
of food adulteration and contamination”
on the structures and dynamics of complex
scattering (SERS).
features on the inside cover of the September
macromolecular systems. Our commitment to
2012 edition of Chem Soc Rev. This
developing methods and technologies in the
MIB researchers using MALD-TOF-MS and
Bruker & MIB – investing in the
future of NMR Spectroscopy
ADAPT – Life in a cold climate:
the adaptation of cereals to
new environments and the
establishment of agriculture in
Europe
Combining genome sequencing and
adaptation to the new environments into
review first introduces some background
area of magnetic resonance spectroscopy is
transcriptome profiling with ecological
which they were being taken. The Brown
into these practices, both historically and
shared by Bruker UK Ltd who has committed 4
niche modelling of a large collection of
group will also compare with demographic
contemporary, before introducing a range
fully funded studentships to the MIB.
historic varieties of barley and wheat
data on early farming communities, which
of the technologies currently available for
landraces collected from different parts of
suggest that in some regions an initial
the detection of food adulteration and
Europe this project aims to identify regions
increase in population size was followed by
contamination. These methods include the
Professor Terry Brown has recently secured
of Europe where early crops underwent
rapid decline, possibly indicating that further
vibrational spectroscopies: near-infrared,
significant funding from the European
evolutionary adaptation in response to
genetic adaptation was needed before crops
mid-infrared, Raman; NMR spectroscopy, as
“Bruker has long maintained an
Research Council to explore the concept of
local environmental conditions. These data
became productive enough to support long
well as a range of mass spectrometry (MS)
interest in structural biology with active
agricultural spread as analogous to enforced
will then be compared with archaeological
term population growth.
techniques, amongst others. This subject area
collaborations in various research
climate change and asks how cereals
information on the rate at which agriculture
is particularly relevant at this time, as it not
projects into method development
adapted to the new environments to which
spread through different parts of Europe,
only concerns the continuous engagement
and applications across an array of
they were exposed when agriculture was
in order to understand whether pauses in
with food adulterers, but also more recent
technology including the development
introduced into Europe during the period
the advance of agriculture were caused
issues such as food security, bioterrorism
of the National EPR Centre. Our
7000–4000 BC.
by the need for crops to undergo genetic
and climate change. It is hoped that this
company ethos and commitment to
introductory overview acts as a springboard
knowledge advancement is shared by
for researchers in science, technology,
the MIB and we are very excited to be
engineering, and industry, in this era of
directly involved in the training of young
systems-level thinking and interdisciplinary
scientists through our sponsorship of
approaches to new and contemporary
four MIB-Bruker studentships aimed at
problems.
developing a strong strategic partnership
with MIB that will ultimately generate
new discoveries and innovations.”
Jeremy Lea
Ribs from the female adolescent skeleton
Bruker UK Ltd
4006 from St. George’s Crypt, Leeds. Bone
formation possibly indicative of pulmonary
1cm
TB is visible on the surface of the ribs
within the area indicated by the boxes.
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41
Manchester Centre for
Biophysics and Catalysis (MCBC)
MCBC is a state-of-the-art cross disciplinary
through temporal analysis of dynamic
to large pharmaceutical companies (ie.
transitions relevant to biological function and
Shell, AstraZeneca, DSM, TgK) on a range of
catalysis from the femtosecond to second
projects. MCBC also works with instrument
timescale.
developers to generate next generation
platform technology centre integrating
biophysical, structural, and computational
MCBC is home to a number of platform
methods to address contemporary problems
technologies in the biophysical and catalysis
in catalysis and the dynamical properties
areas. At Manchester we emphasize the
of biological macromolecules. The MIB
integration of these technologies to address
has recently emerged as a world-leader in
major biological challenges at the molecular
integrated biophysics and catalysis, with
level. This molecular insight is crucial in
capabilities spanning all aspects of biological
developing larger scale understanding of
structure determination, magnetic resonance
biology at the systems level. We also place
spectroscopies, time resolved and single
emphasis on developing new technologies
molecule spectroscopy and biological/
and the translation of molecular-based
chemical computation. By going beyond
research. MCBC develops programmes
simple structure determination of biological
with external partners in most areas of
molecules MCBC is driving the new
research expertise and works with a number
‘dynamics determines function’ paradigm
of industrial partners ranging from SMEs
Robots are already part of the
pharma industry’s development
process, but could they ever
take over completely?
biophysical instruments, for example specialised
applications in laser/infra red spectroscopy,
high pressure NMR spectroscopy and high
pressure optical spectroscopy. State-of-the-art
facilities in the MIB include: anaerobic facilities,
bioengineering and evolution, chemical
biology and synthesis, computation and theory,
electron microscopy, electron paramagnetic
resonance, laser facilities, microfabrication and
nanotechnology, nuclear magnetic resonance,
single molecule approaches, structural
biology, time resolved spectroscopy and x-ray
crystallography facilities.
“…the motivation for our work is partly philosophical and there is a strong view
Ross King, Professor of Machine Intelligence,
that holds that we do not fully understand a phenomenon unless we can replicate
and his colleagues have spent a decade
it: “What I cannot create, I do not understand” [Richard Feynman from The Universe
developing Robot Scientists – machines
in a Nutshell]. Automating science is an excellent test bed for AI as it involves
designed to automate the discovery of
formal reasoning with interaction with the real-world. However the most important
scientific knowledge.
motivation is that we wish to make scientific research cheaper and more costeffective”.
The King group built two Robot Scientists.
“Adam” was designed to understand how
Ross King
the components of cells work together
Professor of Machine Intelligence
Innovation in Action
The MIB pursues and is engaged in challenging research projects that enable us to make significant advances in
science to benefit industry and society. Through innovative research, we can help you advance your business,
solve technical problems, improve your processes, develop new products and build the technical capabilities of
your staff. We understand the importance of adapting the approach to meet the needs of the project.
There are a number of ways for commercial businesses to benefit from the academic expertise fostered in the
MIB. We run a successful programme of networking events with industrial partners and other stakeholders
that focus on developing practical strategies to create short-term, mid-term and long-term relationships for
mutual benefit. Our partnerships range from collaborative research programmes to joint studentships and
instrumentation-technologies development across the chemical, biotechnology and biopharmaceutical sectors.
(functional genomics) and is the first machine
to have discovered some novel scientific
knowledge. New Robot Scientist “Eve” is
designed to automate drug screening and
design. Eve has been applied to the discovery
of leads for neglected tropical diseases such
as malaria, African sleeping sickness, Chagas
disease etc.
Collaborations
Benefits of collaborative research with MIB include:
We actively engage with a wide range of companies from large
• the cost effective trialling and testing of products, drugs and pharmaceutical to smaller SMEs. Existing partnerships include
compounds using University facilities and expertise
companies from the Chemical, Biotechnology and Biopharmaceutical
sectors as outlined in our research portfolio including Bruker, BASF,
GSK, Novartis, Shell, Siemens, Solvay, Syngenta and Unilever.
We offer an unrivalled environment that presents opportunities for
placements in industry across a variety of research disciplines. Our
portfolio of industrially sponsored postgraduate studentships includes
Bruker Ltd, Lonza, Unilever, AstraZeneca, TgK, Chirotech, Shell and
GlaxoSmithKline.
We also host European biotechnology training networks in Industrial
Biotechnology including P4fifty and BIOTRAINS, for the support
for the chemical manufacturing industries and MAGIC (MAGnetic
• the development of close long-term relationships with academic staff to build a relevant and comprehensive portfolio of research and expertise needed to meet your company’s specific needs.
• the transfer of innovative techniques and practices from the laboratory to the manufacturing process
• the direct licensing of innovative technologies and processes
• the accessing of government and European Union funds for academic research that would be out of reach for purely commercial projects
Innovation in Catalysis).
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43
Technology Transfer
Spin-out companies
The University of Manchester Intellectual
C4X, known as Conformetrix, founded
technological platform has been developed
Property Limited (UMIP) assists in the
by DrAndrew Almond, is focused on
based on the fundamental understanding
commercialisation of any innovative
the optimisation of drug discovery and
of the self-assembly of oligo-peptides
technologies and processes that may be
design using NMR-based technology to
across the length scales. This allows the
derived from collaborative research. UMIP
accurately solve bioactive three-dimensional
design of bespoke biocompatible and
has over a 20 year history of Intellectual
molecular structures. Conformetrix Ltd and
biodegradable hydrogels with tailored
Property (IP) commercialisation and works
AstraZeneca signed a research collaboration
mechanical properties and functionality for
closely with MIB to ensure that any IP is fully
agreement under which Conformetrix’s
a range of biotechnological applications.
developed to maximise technology transfer.
proprietary NMR-based technology will be
These hydrogels are composed of an
applied across AstraZeneca’s pre-clinical
entangled network of elongated fibres that
therapeutic pipeline to enhance lead
mimic the structure of extra cellular matrix.
discovery and hit identification.
Their mechanical strength can be tailored
PeptiGelDesign was founded in 2013
by Drs Aline Miller and Alberto Saiani. A
In the FY2012-13 the MIB has secured over
31 invention disclosures which represents
a 48% increase from the previous year and
filed 1 priority patent and 2 new licences.
PharmaKure, founded by Professor Andrew
Doig and Dr Farid Khan, launched in 2012 to
explore new Alzheimer treatments through
For further details of collaboration and
the screening of existing drugs. Pharmakure
partnership opportunities please contact:
is a new drug discovery company focused
on Alzheimer’s disease through the discovery
Dr Ros Le Feuvre
of new uses for old drugs, offering great
E:[email protected]
promise for delivering new therapeutic
T: +44(0)161 306 5184
options to patient care.
to span those of a large range of human
tissues. Moreover the hydrogels can be
functionalised with multiple biologics and
pharmaceuticals. These novel materials
are therefore suitable and proven as drug
delivery vehicles, scaffolds for cell based
therapies and assays as well as tissue
engineering, thereby enabling the next
generation of therapeutic treatments. This
Research Centres,
Institutes and Facilities
Embedded within the Institute are a number of internationally renowned research centres.
research is now being commercialised
through the spin out PeptigelDesign Ltd.
Dr Penny Johnson
E:[email protected]
T: +44(0)161 306 4474
Research Centres
Centre of Excellence in Biocatalysis,
Michael Barber Centre for Collaborative
Manchester Centre for Integrative
Mass Spectrometry
Systems Biology (MCISB)
Biotechnology YES 2012 - MIB
team triumphs in National
competition to be the
biotechnology stars of the future
The competition was hosted by The University
bioscience postgraduate and postdoctoral
Biotransformations and Biocatalytic
The Michael Barber Centre for Collaborative
The MCISB provides a hub for cutting-edge
of Manchester’s Innovation Centre (UMIC)
researchers develop hypothetical business plans
Manufacture (CoEBio3)
Mass Spectrometry is a leading research centre
systems biology research pioneering the
and organised jointly by the BBSRC and
for plausible biotechnology companies. They
devoted to developing mass spectrometry
development of new experimental and
the University of Nottingham’s Institute for
receive help and advice from speakers, mentors
based technologies and their application to
computational technologies and skills necessary
Enterprise and Innovation (UNIEI). Biotechnology
and judges in areas such as intellectual property,
biological problems. Professor Perdita Barran,
for the development of quantitative Systems
Members of Jason Micklefield’s research
Yes is in its 17th year and aims to help
financial planning and marketing.
Waters Chair in Mass Spectrometry has recently
Biology, and their exploitation.
taken up the post of Director.
www.mcisb.org
Enzomax
Development of new biocatalyst-based
processes to meet the changing needs of
industry in the next 10-20 years. CoEBio3
will train graduate and postdoctoral scientists
such that they possess the necessary
combination of skills in chemistry, biology
and engineering needed to support these
(l-r): Brian Law, Anna-winona Struck, Matthew Styles, Sarah Shepherd, James Leigh
changes.
Manchester Centre for Biophysics and
Manchester: Integrating Medicine and
www.coebio3.org
Catalysis (MCBC)
Innovative Technology (MIMIT™)
group secured a place in the final of
a national competition to find the
entrepreneurial bioscientists of the future.
Matthew Styles, Anna-Winona Struck, Sarah
Shepherd, Brian Law and James Leigh formed
team Enzomax and beat off stiff competition
from 377 competitors across 82 teams in
five regional workshops held in October
and November in the Biotechnology Young
Entrepreneurs Scheme (Biotechnology YES)
2012 competition. The team flew the flag
for Manchester in December at the UK finals
held in London. Although the team did not
scoop the top prize, which went to Calvitium
Solutions, they won the category for “Best
consideration of IP strategy” sponsored by
Potter Clarkson.
Enzomax have a proprietary platform
technology, known as Enzomax SHIELD™,
which they use to deliver cost-effective
MCBC is a state-of-the-art cross disciplinary
National Centre for Text Mining
(NaCTeM)
platform technology centre integrating
biophysical, structural, and computational
methods to address contemporary problems
The National Centre for Text Mining
in catalysis and the dynamical properties of
(NaCTeM) is the first publicly-funded text
biological macromolecules. By going beyond
mining centre in the world. The Centre
simple structure determination of biological
provides text mining services in response
molecules MCBC is driving the new
to the requirements of the UK academic
‘dynamics determines function’ paradigm
community leveraging the UK e-Science
through temporal analysis of dynamic
framework, grid technology, relevant
transitions relevant to biological function and
standards and OMII-UK middleware.
catalysis from the femtosecond to second
www.nactem.ac.uk
timescale.
MIMIT™ uses its unique Innovation
Development Process™ to scope
unmet healthcare needs and accelerate
the development of new healthcare
technologies; thereby enabling new
technologies to reach patients faster and
more effectively.
www.mimit.org.uk
www.mcbc.ls.manchester.ac.uk
solutions for maximising the performance of
enzymes in industrial biotechnology.
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45
Research Institutes
Biophysics
The University has established a number
Enquiries: Dr Derren Heyes
of prestigious interdisciplinary Research
[email protected]
Institutes in addition to existing specialist
Tel: +44(0)161 306 5159
research centres and groups. Research
institutes incorporate the acknowledged
research strengths across the University into
core research priorities. Researchers in the
MIB have strong links with the following
institutes:
The Biophysics Facility is one of the largest,
academic ‘Kinetics and Spectroscopy’
facilities for bioscience research in the
world and consists of over £1.5 million of
state-of-the-art instrumentation. We offer
cutting-edge biophysical equipment, which
Photon Science Institute
can be used to study many different chemical
www.manchester.ac.uk/psi
and biological processes over a range of
Institute for Science Ethics and
Innovation
www.isei.manchester.ac.uk
Cancer Research UK Manchester Institute
www.cruk.manchester.ac.uk
timescales and temperatures. The facility is
research facilities in the MIB which are
maintained by dedicated experimental
officers offering flexible and tailored use of
our facilities, ranging from walk-in service
to formal collaborations. Services and
equipment are available to University of
Manchester researchers and external users
from academia and industry.
chemiluminiscence imaging system and a 10
litre wavebag (GE Healthcare) for insect cell
scale up.
The facility collaborates extensively across
departments in the University that includes:
Michael Smith building, AV Hill, Stopford
Building, St Mary’s Hospital, Patterson
Institute and MIB. External collaborators have
been growing over the last two years now
and some examples are Sheffield University,
Abcam, Syngenta, Takeda & Heptares.
Tel: +44(0)161 306 5157
Tel: +44 (0)61 306 5186
Nuclear Magnetic Resonance (NMR)
Gas-phase ion chemistry research provides
This facility includes instrumentation for
spectroscopy is one of the principal
an enhanced understanding of the analytical
the imaging, manipulation or measurement
techniques used to obtain physical, chemical,
techniques that underpin proteomics,
of single biomolecules or single molecule
electronic and structural information about
metabolomics and the investigation of
biochemical reactions. Recent AFM projects
molecules. It is a powerful technique that
other molecules of biological significance.
include imaging of graphene on silicon
can provide atomic resolution information
New developments in quantitative mass
oxide in air, fixed xenopus embryos in PBS,
on the topology, dynamics and three-
spectrometry provide much needed
protein fibrils, mucins, gold nanoparticles,
dimensional structure of molecules in
information for modeling of biological
etched troughs and pits in silico, end to end
solution and the solid state. The breadth
networks, while techniques are being
protein stretching and a selection of cell and
surface indentation experiments on the JPK
CellHesion AFM.
publications in a broad range of high impact
(£250,000 ‘EURenOmics EU FP7 collaborative
spectroscopic tools.
journals.
project & £157,000 from Kidney Research
Additional capabilities include: Mass
The facility offers a range of microscopes
In March 2012 the MIB took delivery of a
Spectrometry (including Secondary Ion Mass
for routine fixed specimen imaging and
new 800 MHz Bruker NMR spectrometer,
Spectrometry (SIMS) and Fourier Transform
specialised microscopes including multimode-
along with upgrades to existing 600 and 500
Ion Cyclotron Resonance (FT-ICR)), Electron
picoforce atomic force microscope (AFM);
MHz spectrometers. These new additions to
Paramagnetic Resonance (EPR), Infrared
JPK cellhesion AFM; Total Internal Reflection
The facility has developed the use of
processes in biological macromolecules
UK) with Professor Paul Brenchley at St
Mary’s Hospital to study the role of the
protein PLA2R in the disease membranous
nephropathy.
our facility will open up a substantial number
and Raman Spectroscopy, Fluorescence
Fluourescence Microscope (TIRFM); Raman
including advanced fluorescence techniques;
of new research programmes focusing on
Spectroscopy (including anisotropy decay).
Laser Tweezers; Fluorescence Correlation
Circular Dichroism (CD) spectroscopy;
the structures and dynamics of complex
Spectrometer (FCS); Typhoon Trio+ Variable
macromolecular systems.
Mode Imaging System for scanning
electrochemical approaches to probe redox
properties of biological molecules using
potentiometry apparatus; Fourier Transform
Infra-Red (FTIR) spectroscopy; Isothermal
titration calorimetry (ITC) and surface
plasmon resonance (SPR).
Complementary spectroscopic techniques
provides protein production services and
of kinetic instruments to study biological and
access to the state-of-the-art instrumentation
chemical reactions on the fs – sec timescale.
Manchester Protein Structure Facility
Enquiries Dr Colin Levy
[email protected]
Tel: +44 (0)161 306 5185
X-Ray crystallography utilises X-ray diffraction
by single protein crystals to elucidate three
dimensional structures at atomic resolution.
The technique plays a pivotal role in
interact with small molecule ligands and
cofactors.
The Facility provides a complete service
pipeline, taking you from purified protein
to crystal structure. Meeting the often rate
dynamics and function. Supported by a suite
limiting challenge of crystallogenesis are two
Manchester Protein Expression Facility
Enquiries Dr Eddie McKenzie
Maintained by a team of dedicated
[email protected]
experimental officers we offer flexible and
Tel: +44 (0)61 306 4170
The facility provides a comprehensive
resource for the high level expression
and scale-up production of recombinant
proteins. Currently we offer a choice of
four expression systems: bacteria, pichia,
insect and mammalian cells. Depending
on particular needs we are able to provide
either small scale production facilities
for biochemical analysis and antibody
production or larger scale production for
We have close links with Bruker who
have contributed four 4-year fully funded
industrial PhD studentships.
MIB has both state-of-the-art very high
magnetic field strength instruments, and
more economical lower field instruments.
understanding how individual amino acids
for the analyses of protein structure,
industry scientists.
[email protected]
Tel: +44 (0)161 306 4229
of a variety of post-translational modifications.
In addition to the above we offer a number
University, other educational institutions, and
Enquiries: Dr Steven Marsden
[email protected]
developed for the analysis and quantification
The Protein Science Facility at the MIB
to researchers and students from across the
Enquiries: Reynard Spiess
[email protected]
NMR measurements makes it unique among
Blanch/Roy Goodacre/Peter Gardner).
formal collaborations. The facility is open
Enquiries: Dr Matthew Cliff
and quality of information attainable from
Protein Science – an integrated approach
tailored service, ranging from walk-in to
Bionanotechnology and Imaging
been named on two successful grants
(Steve Rigby) and Raman spectroscopy (Ewan
carried out in O2-free environment.
Mass Spectrometry
The protein expression team have recently
are available in MIB in EPR spectroscopy
of anaerobic facilities all experiments can be
Nuclear Magnetic Resonance (NMR)
topics and has contributed to a number of
catalytic, binding, structural and dynamical
We have an impressive range of specialist
Biomek FXp liquid handling robot; Syngene
actively involved in a wide range of research
advanced spectroscopic tools to study
Research Facilities
ÄKTAxpress Protein Purification systems;
complimentary high throughput nanolitre
dispensing robots (Mosquito & Phoenix)
allowing rapid screening and optimisation.
The facility also houses two rotating
anode X-ray generators and associated
data collection equipment. These in-house
facilities are further supplemented with
regular synchrotron access.
Secondary Ion Mass Spectrometry (SIMS)
fluorescent and radiolabelled gels and an
Enquiries: Dr Nick Lockyer
microscope with colour and monochrome
[email protected]
cameras.
Tel: +44(0)161 306 4479
Olympus BX51 upright fluorescence snapshot
In addition a large selection of widefield,
SIMS is developed and used for the analysis
confocal and specialist microscopes are
and imaging of chemical and biological
available in the Michael Smith Building
systems, including advanced materials, single
Bioimaging Facility.
cells and biological tissue. The aims involve
Computational Chemistry
Enquiries: Linus Johannissen
[email protected]
Tel: +44 (0)161 306 4559
Simulating protein function and dynamics
using computational methodologies
including protein dynamics & conformational
change (MD simulations); free energy
calculations (umbrella sampling,
metadynamics); ligand binding (docking,
metadynamics) and catalytic mechanisms
novel insights into the chemical and spacial
organisation and function of these systems
at the molecular level.
Nick Lockyer and John Vickerman are
developing applications of SIMS in
areas involving the characterisation and
classification of cells and tissue at the
molecular level. They are also working
closely with industry to develop new
instrumentation and analytical protocols to
advance SIMS applications in biosciences.
(QM & QM/MM calculations).
MassSpec@Manchester
Mass spectrometric research has a long and
rich history at The University of Manchester.
In this network we attempt to bring together
the experience and expertise of these
researchers under one umbrella.
structural studies. Equipment includes
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47
Postgraduate and
Training
“MAGIC” brings Marie Curie
success to Manchester
involved in their research projects.
The MIB and Photon Science Institute (PSI)
founded across research groups in MIB-
have secured a Marie Curie FP7 IDP training
PSI and will enrich the training experience
“Our aim is to train the future
network grant worth 3.4 million euros.
bringing multiple skills embedded in these
generation of leading investigators of
The four year grant entitled “MAGnetic
teams to MAGIC programmes. These novel
biological catalysis/enzymology with
Innovation in Catalaysis”, known as MAGIC,
methods will transform current experimental
a view to developing new enabling
will see the MIB and PSI host 12 Early Stage
capabilities and will be applied to a range
technologies that can advance physical
Researchers (ESR’s) who will be appointed
of important biological catalysts to probe
understanding of catalysis and
to three-year PhD training programmes.
the mechanistic importance of coupled
mechanism. Collaborative research
Hosted at the MIB and PSI this project will
motions and quantum physico-chemical
projects will explore the mechanistic
see Manchester partner with six Universities
effects. Innovative physical sciences magnetic
details of enzyme systems by adopting
(Tokyo, Freiburg, Lund, Joseph Fourier
resonance techniques (NMR and EPR) will be
innovative, versatile and unique
in France, Edinburgh and Copenhagen)
developed and implemented in a life sciences
experimental techniques to probe the
and five companies (AZ, Bruker, TGK,
context to transform studies of enzyme
contributions of motions across multiple
Conformetrix, and SarOMICS) with each
mechanisms and catalysis, and ultimately
spatial and temporal timescales and
ESR closely linked to the international and
rational design.
quantum chemical effects. In turn
The concept of team-based activity is well
industrial partners who will be actively
these novel methods will transform
current experimental capabilities and
will be applied to a range of important
biological catalysts to probe the
mechanistic importance of coupled
motions and quantum physico-chemical
effects.”
The MIB offers a unique environment to carry out multidisciplinary research with open-plan laboratory and
write-up areas designed to promote open communication between researchers from diverse and hybrid
Professor Nigel Scrutton
scientific backgrounds. Home to over 250 PhD students and 80 MSc students we endow our interdisciplinary
Director
investigators with the key skills to enable them to work successfully across the disciplinary interfaces at the
forefront of biotechnology.
In addition to the traditional UK doctoral
chemistry through the isolation, redesign and
In the search for new enzymes and
training programmes we host a number
application of cytochrome P450 enzymes. As
biocatalysts, high-throughput screening
of EU training networks (P4fifty, Biotrains
part of the P4FIFTY network, research groups
methods for catalysis have a key role and they
and MAGIC). Students join a vibrant
at ten European institutions will collaborate
are necessary for screening libraries generated
and dynamic international community of
on trying to address some of these limitations,
either from sampling the biosphere or from
researchers and students from across the
including the following areas: Gene discovery
diverse generation methods. The technique
EU and around the world including China,
for new P450 activity from microbes and
suitable for HTS must be rapid and cost
Egypt, Saudia Arabia, India, Pakistan, USA,
plants; Enabling P450 application through
effective and reflecting the desired functions.
Mexico, Chile and Thailand amongst others.
fusion protein technology; Protein engineering
We offer an unrivalled environment that
presents opportunities for placements
in industry across a variety of research
and bioinformatics; Process technology for the
scale-up of P450-catalysed reactions.
fluorescence based HTS methods for several
biocatalytic reactions. This HTS method will be
innovation. I was delighted to join the MIB as it promotes interdisciplinary, challenge
oriented science that is supported by an outstanding structural biology infrastructure.”
Claudio Santos
Ph.D Biochemistry, 2nd Year Bruker Studentship
used to screen bacterial, plant, fungal (and their
disciplines with a growing number of
Cytochromes P450 (P450s or CYPs) are
mutants) P450 libraries for hydroxylation activity
research students industrially funded
heme-containing oxygenase enzymes that
against a set of standard compounds which
through Bruker UK Ltd, Lonza, Cypex,
catalyse crucial reactions in physiology,
have to give specific reaction with human
Unilever, UCB Pharma, AZ, TgK,
biosynthesis and biodegradation. The power
P450s. Another aspect of MIB efforts will be
Medimmune, Chirotech and Shell.
of P450s can be recruited for the clean, green
to develop P450s active in both conventional
chemical synthesis of important intermediates
organic solvents and also alternative ones (such
in the bulk chemical, pharmaceutical and
as fluorinated solvents) providing engineering
agrochemical Industries. However, their
solutions for large scale application to be
application is frustrated by natural limitations
investigated. The adaptation of existing HTS
P4FIFTY in the search for new
enzymes and biocatalysts
48
using strategies informed by X-ray structure
The MIB team has successfully developed new
“The MIB has a reputation for pushing the boundaries in technology development and
such as low activity, insoluble gene expression
methods is associated with synthesis and testing
P4FIFTY is an FP7 funded European Marie
and the dependence on auxiliary electron
new potential substrates.
Curie Training Network of academic and
transport proteins for full activity, each of
industrial researchers looking to develop
which militate against the scale-up of P450-
enzymatic methods for green oxidation
catalysed reactions.
“The MIB is an exhilarating environment in which to carry out research. I enjoy
associating with peers from around the world, and the up-to-date facilities mean the
research undertaken here is of the highest quality. I also believe that the integration
of different experimental approaches provides a key advantage over other competing
groups and institutions.”
Alex Geddes
Ph.D Biochemistry, 2nd Year Bruker Studentship
49
BIOTRAINS – leading the green
chemical training push
the Centre of Excellence for Biocatalysis,
alternative energy and biomaterials and
Biotransformations and Biocatalytic
has the potential to enable economies to
Manufacture (CoEBio3: www.coebio3.org),
become less dependent on fossil fuels by
The ‘European biotechnology training
this four-year project involves eleven partners
employing the power of natural biocatalysts
network for the support of the chemical
from academia and industry who will recruit
and modern manufacturing techniques
manufacturing industries’ (BIOTRAINS)
and train research fellows and another
to deliver safer and less-environmentally
programme brings together microbiologists,
six industrial partners who are offering
damaging industrial methods. It is a term
enzymologists, chemists, engineers and
placement training that is expected to make
used mainly in Europe for the application of
process development experts involved in the
a major contribution to efforts to replace
nature’s catalysts, such as enzymes and cells,
training of the next generation of scientists
traditional chemical manufacturing – reliant
in biotechnology for industrial purposes.
who will develop green manufacturing
on highly toxic chemicals and solvents – with
The use of the word ‘white’ distinguishes
methods for the chemical industry. Led
so-called ‘white biotechnology’. The term
it from other biotechnologies such as ‘red’
by Professor Nicholas Turner, Director of
covers the manufacturing of chemicals,
(medicinal) and ‘green’ (plant) biotechnology.
Science and Society
Informing... consulting... collaborating
The University of Manchester is committed to the discovery and dissemination of knowledge and seeks to lead
on public engagement in all forms, providing expertise in public discourse and policy development, listening to
the wider community, and involving the public in its work.
We work closely with the University Public
students developed a number of laboratory
Interactive stands included: Protein Science
Engagement team, Manchester Museum and
demonstrations that covered topics as
| Genomics (RNA/DNA) | Protein Structural
the Museum of Science and Industry (MOSI)
diverse as NMR, protein expression and
Biology | Enzyme Reactions | Spectroscopy/
to deliver events and activities including the
robotics. A variety of interactive stands
Spectrometry | Systems and Computational
Manchester Science Festival and National
showcased the rich array of MIB research
Biology | Microfluidics/nanoscale devices
Science and Engineering week.
from the developing enabling technologies
| Biofuels and Energy | Microbiology |
(including micro fluidics, nanotechnology and
Glycobiology and Photochemistry.
We continue to host students as part of the
Nuffield Bursary Placement Scheme enabling
students to work alongside professional
scientists, technologists, engineers and
spectrometry/spectroscopy), protein science
and genomics through to systems and
computational biology.
Tour demonstrations included: Protein
Structure | Mass spectrometry | NMR | Protein
Expression | Robotics | Enzyme reactions.
mathematicians. In particular the scheme
encourages from schools in difficult social
circumstances, and students who do
not have a family background of higher
education or STEM professions.
On Friday 9 November 2013 the MIB
“... a distinctive feature of the
opened its doors to 200 A-A/S students
University is its commitment to a social
from 12 schools/colleges from across the
responsibility agenda. This ethos is
North of England providing them with a
embedded in our outreach activity
unique opportunity to visit a world class
at the MIB and we are committed to
interdisciplinary research institute. Students
engaging with our wider community
witnessed and participated in a number
with the aim of increasing awareness,
of activities throughout the day including
interest, and understanding of science
interactive research stands followed by
and hopefully inspiring the next
guided tours of the research laboratories
generation of scientific leaders”.
with an opportunity to talk with researchers
about their work. MIB postdocs and research
Dr Rosalind Le Feuvre
MIB’s Research and Planning Manager
50
51
HIGHLIGHT : Royal Society
Summer Exhibition
The stand demonstrated how the study of
has since had over 700 views. They were
carbohydrates such as sucrose, starch, pectin
also successful in the Royal Society Games
and alginate can help improve many aspects
Jam competition with their game, ‘Cell
of our lives from producing renewable
Invaders’, which was voted the best game
energy and materials to generating new
at the exhibition and won £2,000 worth
medicines. How cell sugars interact with
of development and is now available to
foreign molecules have applications in a
download on PC and iPad.
variety of areas, including improving human
fertilisation therapies, developing anti flu
medicines and diagnostic tools, and creating
new anti-cancer treatments. Identifying
the difference in glycocalyx between cells
can help scientists distinguish between
pandemic, seasonal and bird flu and develop
the correct therapies for flu outbreaks. As the
“It was very exciting to be selected to
glycocalyx also differs between individuals, it
exhibit at the Royal Society and we
provides a method for producing advanced
In summer 2013 Professor Sabine Flitsch
very much enjoyed interacting with the
diagnostic tools for personalised medicines.
hosted an exhibition stand entitled ‘The
students. Our exhibit demonstrated
One of the main exhibition activities was
Complex Life of Sugars’ at the prestigious
how the study of these sugars can
focused on cell surface sugars and visitors
Royal Society Summer Exhibition alongside
help improve many aspects of our lives
were encouraged to build a cell surface sugar
collaborators from Imperial College London,
from producing renewable energy and
and explore its interaction with cell invaders
University of Liverpool, John Innes Centre
materials to generating new medicines.
both on a cell surface and also a gold
and the University of Leeds. The exhibition
Understanding the glycocalyx and its
glycan array. This activity was very popular
was visited by over 12,500 people including
interaction with other molecules will
and designed to highlight and directly
students, teachers, public, scientists, media,
provide a wide range of opportunities
promote the GlycoBioM work. As part of
potential donors/key decision makers and
for the development of new foods,
the exhibition the team also commissioned
celebrities. This stand was part of the EU
medicines and healthcare treatments”
a three minute animation which provided
funded GlycoBioM project featured in the
an introduction and overview of the whole
Sabine Flitsch
Biomedical and Healthcare section.
area of carbohydrate science. This video
Professor of Chemical Biology
FACULTY HONOURS
FACULTY
The Institute is home to approximately 52 Research groups with over 500 staff and students from across
the Faculties of Engineering and Physical Sciences, Life Sciences and Medical and Human Sciences.
Faculty of Life Sciences
ALMOND, Andrew - 3D-structure
and function of biologically important
oligosaccharides and polysaccharides.
BELLA, Jordi - extracellular matrix proteins:
structure, design possibilities and biomaterial
applications.
BLANCH, Ewan - biostructural analysis using
Raman spectroscopies.
BREITLING, Rainer - metabolomic systems
biology and postgenomic data analysis
BROWN, Terry - biomolecular archaeology –
using DNA to study the past.
Binding of the egg and sperm using cell surface sugars
Nature’s Catalyst stand
© The University of Manchester
as part of National Science and Engineering Week
BUCKLEY, Mike - determination of speciesspecific biomarkers in bone for studying
vertebrate palaeobiodiversity.
DIXON, Neil - RNA as a tool, RNA as a target;
small-molecule inducible gene expression control.
DOIG, Andrew - protein structure,
bioinformatics, amyloidosis.
GOLOVANOV, Alexander - biology: structure,
mechanism and engineering of new properties.
HAY, Sam - quantum and theoretical
biophysics.
HAYES, Finbarr - molecular engineering of a
DNA trafficking nanomachine.
LEYS, David - structural biology to look
at new metabolic pathways/novel enzymes
systems; structural insights guide rational
engineering/synthetic biology applications.
LU, Hui - redox regulation and biogenesis of
mitochondrial proteins.
MUNRO, Andrew - structure and
enzymology of biotechnologically and
biomedically relevant redox enzymes.
PRINCE, Steve - structural biophysics of
membrane proteins and protein-protein
interactions.
RIGBY, Stephen - biological electron
paramagnetic resonance (EPR) spectroscopy
and related techniques.
SCRUTTON, Nigel - enzyme biophysics,
structure and mechanism, quantum
enzymology, enzyme engineering,
biocatalysis, biofuels.
TAKANO, Eriko - synthetic biology of
bioactive molecules/antibiotics.
WALTHO, Jon - NMR investigations of
protein structure and dynamics.
WARWICKER, Jim - models for structural
cell biology.
Faculty of Medical and Human Sciences
Institute of Information and Repair
BAYAT, Ardeshir - wound healing, tissue repair & regeneration, bio-
MILLS, Clare - why are some proteins allergens and not others; what
surgical engineering.
makes certain types of foods or pollens more allergenic; why do only
some people become allergic?
Institute of Population Health
DAY, Philip - single cell analyses within heterogeneous populations of cancer cells
52
53
Royal Society Wolfson Research Merit Award
Faculty of Engineering and Physical Sciences
Currently three members of our faculty hold prestigious Royal Society Wolfson Research Merit Awards for their exceptional contribution to their
School of Chemical Engineering and Analytical Science
given research fields. Jointly funded by the Wolfson Foundation, the Royal Society Wolfson Research Merit Award recognises talented scientists of
CURTIS, Robin - weak protein-protein
GODDARD, Nick - microfluidics; sensors
SUTCLIFFE, Mike - computational
interactions, protein aggregation,
(electrochemical/optical); high throughput
enzymology & protein modelling.
bioprocessing, biomolecular
platforms; microseparations (electrokinetic);
thermodynamics.
mutiphase microfluidics; micro- and nano-
De VISSER, Sam - computational studies of
enzyme mechanism and function.
GARDNER, Peter - vibrational spectroscopy
of bio and biomedical systems.
fabrication.
MILLER, Aline – application of physical
principles to mimic, manipulate and improve
biomolecular self-assembly to create
materials for regenerative medicine.
outstanding achievement and potential.
Professor Sabine Flitsch
Professor Nicholas Turner
Professor Nigel Scrutton
WESTERHOFF, Hans - integrative systems
Glycoarrays for studying carbohydrate-
New Biocatalysts by Design and Evolution
Catalysis by enzymes - beyond the transition
biology.
protein interaction
state theory paradigm
YUAN, Xue-Feng - rheology of complex fluids/
soft matter such as biofluids and biomaterials
in living system: quantitative rheological and
structural characterisation under physiological
Philip Leverhulme Award
conditions, integrated multiple scale modelling.
Dr Aline Miller has been awarded a Philip Leverhulme Award for her work on “engineering the self-assembly of biomolecules for regenerative
medicine”. The prize recognises rising stars of research, whose work has already made an international impression.
School of Chemistry
BARRAN, Perdita – mass spectrometry;
KEANE, John – development of clinical
POPELIER, Paul - predictive modelling of
instrument development and IM-MS
decision support systems (DSS) and analytics
structure and dynamics from first principles;
fundamentals.
of multi-modal (structured, semi-structured,
drug design; chemical insight from modern
unstructured, image) data for bio-health
wave functions.
FLITSCH, Sabine - glycosciences and
biocatalysis.
GARDINER, John - carbohydrate chemistry/
chemical biology, biocatalysis, dendrimer
synthesis and heterocyclic bioorganic
chemistry.
GOODACRE, Roy - integrative ’omic
analyses and vibrational spectroscopy for
understanding biological systems.
HENCHMAN, Richard - biomolecular
structure and dynamics.
applications.
TURNER, Nicholas - discovery and directed
KELL, Douglas - development and
evolution of tailored biocatalysts: applications
application of novel analytical methods at the
in industrial biotechnology including fine
interface between postgenomic biological
chemicals, pharmaceuticals and biofuels.
systems, quantitative bioanalytical science and
machine learning, with a special emphasis on
evolutionary computing and systems biology.
LOCKYER, Nick - Imaging Mass Spectrometry
(SIMS), instrument development.
WEBB, Simon - supramolecular chemistry,
biomimetics, understanding biomembrane
behaviour, biosensor design.
Fellows
Dr Chris Blanford
Dr Sam Hay
Dr Alberto Saiani
EPSRC Career Acceleration Fellowship
BBSRC David Phillips Fellowship
EPSRC Research Fellow
Three-dimensional laccase electrodes for
Linking experiment to theory: Quantum
Developing a technological platform based
miniaturised fuel cell power sources
entanglement during enzyme catalysis
on the fundamental understanding of
Dr Mike Buckley
Professor Paul Popelier
Royal Society University Research Fellowship
EPSRC Established Career Fellowship
Molecular timers
Reliable computational prediction of Professor Nigel Scrutton
molecular assembly
EPSRC Established Career Fellowship in
peptide self-assembly for the design of novel
WONG, Lu-Shin - combining chemical
biomaterials
biology and nanotechnology applications in
Dr Neil Dixon
Catalysis
MICKLEFIELD, Jason - chemical biology and
the life sciences: Bioconjugation and surface
BBSRC David Phillips Fellowship
Catalysis in motion: accessing how fast
synthetic biology.
chemistry towards nanoscale protein arrays.
Development and application of next
motions facilitate catalysis through pump-
generation synthetic biology tools
probe and fast time resolved spectroscopies
School of Computer Science
ANANIADOU, Sophia – biomedical text
KING, Ross - interface between computer
mining, information extraction, terminology
science and biology/chemistry.
management, semantic interoperability of
resources.
MCNAUGHT, John – text mining.
MENDES, Pedro - computational systems biology.
MIB Fellowship Opportunities
NENADIC, Goran- text mining and automatic
knowledge structuring (ontologies, concept
maps) in life sciences and health-care.
The MIB actively promotes new career
and culture, all specifically designed to remove
reach their full potential. Additional start up
track research fellowships at the interface
the barriers between disciplines and to
monies may also be available depending on
between engineering, the physical sciences
promote innovative science.
the nature and level of the externally funded
and bioscience. Applications are encouraged
School of Materials
from proactive individuals keen to participate
BLANFORD, Chris - sensitive measurements of protein–surface
SAIANI, Alberto - understanding the chemical architecture -
in interdisciplinary research and interact in
interactions in electrocatalytic enzymes.
thermodynamic - structure - physical property correlations in complex
key societal and strategic research areas of
polymeric systems.
interest to the MIB. For further information
on our fellowship scheme visit our web
pages at www.mib.ac.uk.
School of Mechanical, Aeronautical and Civil Engineering
BARTOLO, Paulo - biomanufacturing and computer-aided design of scaffolds for tissue engineering
54
We offer an attractive fellowship extension
scheme for fellows bringing in 4-5 years of
external funding (regardless of the source of
the fellowship, BBSRC/EPSRC etc), whereby
we will top up fellowships by 1 or 2 years
additional support. We are confident in the
quality of the fellows we wish to recruit
Our research facilities are outstanding offering
and recognise the importance of stability at
a unique infra-structure, research environment
this career stage to enable our fellows to
research fellowship. These fellowships are
seen as early stage entry into independent
academic careers at Manchester. Throughout
the 6-year period you will benefit from close
manager and mentor support from senior
colleagues in the MIB. You will become a
member of one of the University Faculties Human and Medical Sciences (FMHS), Life
Sciences (FLS) or Engineering and Physical
Sciences (EPS).
55
Douglas Kell honoured in Queen’s New Year’s Honours 2014
Professor Douglas Kell CBE MS DPhil FSB FLSW FAAAS
Chair in Bioanalytical Science
Douglas Kell was awarded a CBE for services to science and research in the Queen’s New
Year’s Honours 2014. He has been a pioneer in many areas of computational biology and
experimental metabolomics, including the use of evolutionary, closed-loop methods for
optimisation. He also contributed to the discovery of the first bacterial cytokine, currently on
trial as part of a vaccine against tuberculosis.
Douglas studied at Oxford University focusing on the development and exploitation of novel
methods for the study of (mainly microbial) bioenergetics. He was awarded a Personal Chair at
the University College of Wales (now Aberystwyth University) in 1992 and from 1998-2002 was
Director of Research of the Institute of Biological Sciences. He co-founded Aber Instruments,
that received the Queen’s Award for Export Achievement in 1998.
In 2002 he accepted an RSC/EPSRC-funded Chair in Bioanalytical Sciences at UMIST. From
2005-2008 he was Director of the Manchester Centre for Integrative Systems Biology at The
University of Manchester. From 2008 until 2013 he was Chief Executive of the Biotechnology
and Biological Sciences Research Council (BBSRC).
He has a Doctor of Science Honoris Causa from Cranfield University (2011), and is a Fellow of the
Learned Society of Wales (2012), of the American Association for the Advancement of Science
(2012), and of Aberystwyth University (2013). He has published over 400 scientific papers with
>18,000 citations in WoK (H-index 72). In Google Scholar H=83 and citations >26,000.
Selected Publications
Amaral M, Levy C, Heyes DJ, Lafite P, Outeiro TF,
Giorgini F, Leys D, Scrutton NS. Structural basis of
kynurenine 3-monooxygenase inhibition. Nature
2013 496(7445):382-5.
Brewster VL, Ashton L, Goodacre R. Monitoring
guanidinium-induced structural changes in
ribonuclease proteins using Raman spectroscopy
and 2D correlation analysis. Anal Chem. 2013
85(7):3570-5.
Dunstan MS, Barkauskaite E, Lafite P, Knezevic CE,
Brassington A, Ahel M, Hergenrother PJ, Leys D,
Ahel I. Structure and mechanism of a canonical
poly(ADP-ribose) glycohydrolase. Nat Commun.
2012 3:878.
doi: 10.1021/ac303265q
doi: 10.1038/ncomms1889
Bester J, Buys AV, Lipinski B, Kell DB, Pretorius
E. High ferritin levels have major effects on the
morphology of erythrocytes in Alzheimer’s disease.
Front Aging Neurosci. 2013 5:88.
Castangia R, Austeri M, Flitsch SL. Enzymatic amine
acyl exchange in peptides on gold surfaces. Angew
Chem Int Ed Engl. 2012 51(52):13016-8.
doi: 10.3389/fnagi.2013.00088
doi: 10.1002/anie.201205404
Durigon R, Wang Q, Ceh Pavia E, Grant CM, Lu H.
Cytosolic thioredoxin system facilitates the import
of mitochondrial small Tim proteins. EMBO Rep.
2012 13(10):916-22.
doi: 10.1038/nature12039
Paulo Bártolo joins the MIB
Professor Paulo Bartolo BEng, MSc, PhD
Chair in Advanced Manufactuirng
Paulo Bártolo joins the MIB in Spring 2014 from Polytechnic Institute of Leiria, Portugal. Paulo
holds a PhD degree in Polymer Physics from the University of Reading (UK) and a Master of
Science and “Licenciatura” in Mechanical Engineering, both from the Technical University
of Lisbon (Portugal). His research interests focus on biomanufacturing and computer-aided
design of scaffolds for tissue engineering. He developed different bottom-up and top-down
approaches for bone, cartilage and skin applications. The design of smart and functionally
graded scaffolds to promote tissue interfaces is also an important topic of his research. He
investigated the relationship between the material processing and the mechanical, biological
and degradation characteristics of scaffolds, as well the fabrication of scaffolds with controlled
anisotropy. Different materials (PCL, PLA, PCL/PLA, PCL/HA, PCL/TCP, PCL/graphene, PCL/
bioglass, Alginate, Dextran) and cell lines (fibroblasts, keratinocytes, osteoblasts, chondrocytes
and hMSCs) were used in these research works.
Paulo Bartolo is author and co-autor of more than 400 publications in journal papers, book
chapters and conference proceeding papers. He also edited 13 books and holds 10 Portuguese
Patents. His research work has been published in high impact factor journals like Progress
in Polymer Science, Nanomedicine, Acta Biomaterialia, Biofabrication Journal, Carbohydrate
Polymers. He is also Editor-in-Chief of Virtual and Physical Prototyping Journal published by
Taylor&Francis, and member of the Editorial Board of several Journals like the Biofabrication
Journal, the Rapid Prototyping Journal, the International Journal of Precision Engineering and
Manufacturing, the Journal of Biomaterials and Tissue Engineering, the ISRN Tissue Engineering
and the International Journal on Mechatronics and Manufacturing Systems.
doi: 10.1038/embor.2012.116
Blanford CF. The birth of protein electrochemistry.
Chem Commun (Camb). 2013 49(95):11130-2.
doi: 10.1039/c3cc46060f.
Barkauskaite E, Brassington A, Tan ES, Warwicker J,
Dunstan MS, Banos B, Lafite P, Ahel M, Mitchison
TJ, Ahel I, Leys D. Visualization of poly(ADP-ribose)
bound to PARG reveals inherent balance between
exo- and endo-glycohydrolase activities. Nat
Commun. 2013 4:2164.
doi: 10.1038/ncomms3164
Cawley A, Warwicker J. eIF4E-binding protein
regulation of mRNAs with differential 5’-UTR
secondary structure: a polyelectrostatic model for a
component of protein-mRNA interactions. Nucleic
Acids Res. 2012 40(16):7666-75.
doi: 10.1093/nar/gks511
doi: 10.1039/c2cs35138b
Chesters C, Wilding M, Goodall M, Micklefield J.
Thermal bifunctionality of bacterial phenylalanine
aminomutase and ammonia lyase enzymes. Angew
Chem Int Ed Engl. 2012 51(18):4344-8.
doi: 10.1002/anie.201200669
Both P, Green AP, Gray CJ, Sardzík R, Voglmeir J,
Fontana C, Austeri M, Rejzek M, Richardson D, Field
RA, Widmalm G, Flitsch SL, Eyers CE. Discrimination
of epimeric glycans and glycopeptides using IM-MS
and its potential for carbohydrate sequencing. Nat
Chem. 2014 (1):65-74.
Ghislieri D, Green AP, Pontini M, Willies SC, Rowles
I, Frank A, Grogan G, Turner NJ. Engineering an
enantioselective amine oxidase for the synthesis of
pharmaceutical building blocks and alkaloid natural
products. J Am Chem Soc. 2013 135(29):10863-9.
doi: 10.1021/ja4051235
Cowcher DP, Xu Y, Goodacre R. Portable,
quantitative detection of Bacillus bacterial spores
using surface-enhanced Raman scattering. Anal
Chem. 2013 85(6):3297-302.
doi: 10.1021/ac303657k
doi: 10.1038/nchem.1817
Bouwman AS, Kennedy SL, Müller R, Stephens
RH, Holst M, Caffell AC, Roberts CA, Brown TA.
Genotype of a historic strain of Mycobacterium
tuberculosis. Proc Natl Acad Sci U S A. 2012
109(45):18511-6.
Ellis DI, Brewster VL, Dunn WB, Allwood JW,
Golovanov AP, Goodacre R. Fingerprinting food:
current technologies for the detection of food
adulteration and contamination. Chem Soc Rev.
2012 41(17):5706-27.
Gray CJ, Weissenborn MJ, Eyers CE, Flitsch SL.
Enzymatic reactions on immobilised substrates.
Chem Soc Rev. 2013 42(15):6378-405.
doi: 10.1039/c3cs60018a
Dixon N, Robinson CJ, Geerlings T, Duncan
JN, Drummond SP, Micklefield J. Orthogonal
riboswitches for tuneable coexpression in bacteria.
Angew Chem Int Ed Engl. 2012 51(15):3620-4.
doi: 10.1002/anie.201109106
Hamrang Z, Rattray NJ, Pluen A. Proteins behaving
badly: emerging technologies in profiling
biopharmaceutical aggregation. Trends Biotechnol.
2013 31(8):448-58.
doi: 10.1016/j.tibtech.2013.05.004
doi: 10.1073/pnas.1209444109
56
57
Hansen SU, Miller GJ, Jayson GC, Gardiner JM.
First gram-scale synthesis of a heparin-related
odecasaccharide. Org Lett. 2013 15(1):88-91.
doi: 10.1021/ol303112y
Leys D, Adrian L, Smidt H. Organohalide
respiration: microbes breathing chlorinated
molecules. Philos Trans R Soc Lond B Biol Sci. 2013
368(1616):20120316.
doi: 10.1098/rstb.2012.0316
Hansen SU, Miller GJ, Cole C, Rushton
G, Avizienyte E, Jayson GC, Gardiner JM.
Tetrasaccharide iteration synthesis of a heparin-like
dodecasaccharide and radiolabelling for in vivo
tissue distribution studies. Nat Commun. 2013
4:2016.
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