School of Science and Technology –
Vice-Chancellor’s Researcher
Development Scheme
Broad Areas of Research – General
Engineering
Biomaterials, Molecular Science, LCD
microfluidics, X-ray and MRI Imaging
Technologies.
Important note: Projects within the School of Science and Technology may have
the option of joining a new, University Alliance-sponsored, national Doctoral
Training Alliance in Applied Biosciences for Health, in which students will be part
of an exciting multidisciplinary cohort of postgraduate students and supervisors,
and benefit from regular networking and training opportunities through
attendance at regular national meetings, including residential summer schools,
throughout their PhD studies.
Project Titles (descriptions below)
1. Prof Carl Brown – Liquid Crystal Microfluidics.
2. Prof. Paul Evans – High-speed Contraband Identification by X-ray Diffraction.
3. Dr. Rob Morris – Magnetic Particle Imaging for Stem Cell Tracking.
4. Prof. Carole Perry – Towards understanding the role of ‘silicon’ in life.
5. Prof. John Wallis – Structural Models for the Study of Carbonyl/Carbonyl n-pi*
Interactions – a New Stabilising Feature of Macromolecules.
1.
Prof Carl Brown – Liquid Crystal Microfluidics
Nematic liquid crystal materials are now ubiquitous in mobile, projection and large screen
home cinema displays. These materials tend to have anisotropic properties, including
exhibiting different electrical polarisabilities, refractive indices, and viscosities along
different directions. The tendency of the molecules to align with the direction of an applied
electric field is exploited in LCDs to create an electro-optical effect in which the light
transmission of each pixel is controlled by a switching waveform.
This project will investigate the flow of nematic liquid crystals in and across different closed
and open microfluidic confinement geometries. In a moving nematic layer the local
molecular orientation, characterized by the n-director, is determined by the balance of
torques arising from the direction and magnitude of any applied electric fields, the local
flow direction, and the elastic coupling transmitted from the molecular anchoring at the
confining solid surfaces. This means that the effective viscosity, and hence the flow rate,
can be modulated by varying the magnitude of an applied voltage.
Confinement in particular flow geometries, such as tubes and rectangular cross section
channels, can additionally lead to sudden changes in the n-director orientation and regions
of local melting of the nematic molecular ordering. These regions are referred to as
disclinations and the project will investigate how control of disclination creation, position,
and annihilation via novel surface patterned geometries can be exploited for controlling
flows in microfluidic systems.
Specific qualifications/subject areas required of the applicants for this project:
In order to be eligible to apply, you must hold, or expect to obtain, a UK Master’s degree
with a minimum of a merit, and/or a UK 1st Class/2.1 Bachelor’s degree (or equivalent
qualifications according to NARIC) in Physics, Materials Science or related discipline. The
minimum English language proficiency requirement is IELTS 6.5 or TOEFL 560/iBT 94-95.
For informal discussion regarding the project, please contact:
[email protected]
2.
Prof. Paul Evans – High-speed Contraband Identification
by X-ray Diffraction
Materials discrimination for security screening places significant technical and
socioeconomic demands upon contemporary analytical approaches. Conventional X-ray
diffraction techniques, while possessing the required high specificity and sensitivity in a
lab environment, are totally unsuitable for the high-speed inspection of extended
objects. In response to this problem we propose to combine two disruptive technologies
namely; focal construct geometry (FCG) X-ray diffraction and pixelated energy resolving
sensing. This integrated approach is conceived to realise ‘real-time’, tuneable detection
capability. X-ray diffraction identifies materials from their atomic spacing (not ‘average’
atomic number and density like current scanners). Therefore, the project aim is to
develop detection principles and techniques that are applicable to a wide range of
contraband including explosives/precursors, narcotics, alcohol, fruit, ivory, hardwoods.
The work will also address the issue of identifying contraband within cluttered luggage or
packages, without manual searches or handling the items.
The project will provide an original contribution to knowledge at a number of different
levels in terms of X-ray collection methods, processing and analysis. The experiment work
will employ the state-of-the-art X-ray facilities contained within the RFB Super lab at
Nottingham Trent University. In addition, work will also be undertaken at collaborating
institutions including government labs, industry and other research intensive universities.
This exciting multidisciplinary project would suit a highly motivated individual interested
in X-ray physics/sensing/imaging, computational imaging, signal analysis/PCA,
modelling/maths and simulation and or material science.
The successful candidate will benefit from being part of a highly experienced team of
researchers, with a track record of world leading innovation in the field of X-ray security
imaging. This work has attracted around £5 million research funding from UK and US
governments over recent years. The group produces 4* journal papers and significant
Patents and intellectual property. Examples of recent high quality publications (top 5% of
subject category) can be downloaded from the Optics Express website at
http://www.opticsinfobase.org/ (by entering a search under “annular x-ray”).
Specific qualifications/subject areas required of the applicants for this project:
Minimum of 2:1 BSc (Hons) Physics or Engineering or (dependent upon options/project
and experience; computing/mathematics, forensic science or materials science).
For informal discussion regarding the project, please contact:
[email protected]
3.
Dr. Rob Morris– Magnetic Particle Imaging for Stem Cell
Tracking
It is well known that one of the key factors affecting the efficacy of stem cell therapy is
the successful homing and engraftment of cells at the desired site [1]. The most commonly
employed strategy for identifying the location of such populations is magnetic resonance
imaging (MRI) of Superparamagnetic Iron Oxide Nanoparticle (SPION) labeled stem cells
provide negative contrast. For the most part, this negative contrast is impossible to resolve
from other anatomical features such as air pockets as are common in for example joints.
A promising application of stem cell therapy is in the treatment of Osteoarthritis (OA)
which is a debilitating condition which results in the loss of cartilage and damage to the
ends of the bones in joints. Stem cell therapy offers an exciting treatment option for OA
where mesenchymal stem cells (MSC) may be injected into joints to reform the damaged
cartilage and bone. Unfortunately, in pre-clinical testing, the resolution of MRI and the
extent to which the negative contrast radiates from the site of the SPIONs makes it
impossible to accurately determine the quantity of cells present.
Magnetic particle spectroscopy and magnetic particle imaging have been shown to be
valuable tools in assessing the effectiveness and determining the location of SPION labeled
stem cell populations although thus far, the instruments developed for this purpose have
been constructed to entirely encompass the sample and perform imaging or spectroscopy
in smaller areas of interest.
In this project we will develop a miniaturised system, for which the active elements can
be worn around the joint of therapy, allowing on-line quantitative monitoring of the cells
population and allowing for improved assessment of the therapeutic success. Furthermore,
this system will also take useful steps towards a system which is suitable for long term
monitoring of clinical stem cell therapy. This project will involve the construction of the
coil system for generation and detection of the magnetic fields as worn by the subject and
production of a lightweight portable system to produce and collect the necessary signals.
The system will then be used to detect the quantity of labeled cells present in in vitro
samples.
References
1. Reddy, A. M., Kwak, B. K., Shim, H. J., Ahn, C., Lee, H. S., Suh, Y. J., & Park, E.
S. (2010). In vivo Tracking of Mesenchymal Stem Cells Labeled with a Novel
Chitosan-coated Superparamagnetic Iron Oxide Nanoparticles using 3.0T
MRI.Journal of Korean Medical Science, 25(2), 211–219.
Specific qualifications/subject areas required of the applicants for this project:
At least 2:1 BSc in physics or associated discipline.
For informal discussion regarding the project, please contact:
[email protected]
4.
Prof. Carole Perry – Towards understanding the role of
‘silicon’ in life
The role of the element ‘silicon’ in life is not understood. There are hints from our work
and that of others that it has both biochemical and structural roles but evidence is patchy.
Our contribution to research in this area arises from investigations into the role that
‘silicon’ plays in novel composite biomaterials we develop for dental/ bone repair1,2 as well
as fundamental structural studies aimed at identifying the location of ‘silicon’ in biological
tissues,3 the mechanisms of interaction between silica and biomolecules 4-7 and the
spectroscopic behaviour of new chemical markers for silica.8 From our recent published
studies we have identified upregulation of specific biomolecules including collagen and
bone morphogenic proteins for cells exposed to biomaterials incorporating silica and
identified the chemistry behind the silicaphilic fluorescence of a dye that has been used by
many to identify the location of silica in biological tissues. We are now in a strong position
to make significant advances in our understanding of the role of silicon in life. This project
will advance our understanding of:
1. The biochemical role, through measurement of ‘silicon-biomolecule’ interactions in
aqueous media by novel application of isothermal titration calorimetry, and
2. The structural role, by localization of key molecules involved in biosilica formation.
This aspect of the project will require the synthesis and characterization of novel
fluorescently labelled polyamines/ peptides and the monitoring of their location and
interaction characteristics in living organisms including diatoms using fluorimetric
spectroscopy, confocal microscopy and FRET measurements.
Professor Perry is a world leader in the area of silica chemistry and additionally has a
strong externally respected research profile in the area of biomaterials, particularly those
based on silica. The PhD student will join a research team active in both the development
of new materials for biomedical applications and in advancing our knowledge of the
fundamentals of silica biomolecule interactions. The project will involve aspects of organic
synthetic chemistry to develop new silicaphilic probes and spectroscopic and structural
studies of biomolecule mineral interactions.
References
1. A.J. Mieszawska et al., (2010) Nanoscale Control of Silica Particle Formation via
Silk-Silica Fusion Proteins for Bone Regeneration Chem. Mater. 22(20), 5780-5785
2. A.J. Mieszawska et al., (2010) Osteoinductive silk-silica composite biomaterials for
bone regeneration Biomaterials 31( 34), 8902-8910
3. H.A. Currie and C.C. Perry (2009) ‘Chemical evidence for intrinsic ‘Si’ within
Equisetum cell walls’ Phytochem, 70(17-18), 2089-2095
4. S.V. Patwardhan et al., (2012) Chemistry of Aqueous Silica Nanoparticle Surfaces
and the Mechanism of Selective Peptide Adsorption. J. Am. Chem. Soc. 134, 62446256
5. V. Puddu and C.C. Perry (2012) Peptide adsorption on silica nanoparticles: evidence
of hydrophobic interactions. ACS Nano 6(7) 6353-6363
6. V. Puddu and C.C. Perry (2014) Interactions at the silica-peptide interface: the
influence of particle size and surface functionality Langmuir 30(1) 227-233
7. F.S. Emami et al., (2014) Prediction of Specific Biomolecule Adsorption on Silica
Surfaces as a Function of pH and Particle Size, Chem. Mater. 26(19) 5725-5734
8. M. Parambath et al., (2015) The nature of the silicaphilic behaviour of PDMPO, PCCP
submitted
Specific qualifications/subject areas required of the applicants for this project:
MChem/ MSci/ BSc Chemistry/ biochemistry/ biophysics/ natural sciences minimum grade
2:1.
For informal discussion regarding the project, please contact:
[email protected]
5.
Prof. John Wallis – Structural Models for the Study of
Carbonyl/Carbonyl n-pi* Interactions – a New
Stabilising Feature of Macromolecules.
It has been proposed recently that n-π* interactions between the lone pair of a carbonyl
oxygen atom and the anti-bonding orbital of a second carbonyl group provide a stabilising
C=O···C=O interaction (ca. 1-2 kcal mol-1) which plays an important role in stabilising the
conformations of both small molecules, such as aspirin, and also proteins and polymers.1
Indeed it is suggested that this interaction type should be included in molecular modelling
computer programs along with hydrogen bonding, dipole-dipole interactions etc. for
prediction of macromolecular conformations in materials chemistry and biomolecular
science, since the properties of these systems depend critically on all these interactions.
Furthermore, the interaction modifies the properties of the groups involved, with
implications for enzyme action. The n-pi*interactions are characterised by O···C contacts
within the expected van der Waals separations and small pyramidalisations of the carbon
atom geometry, but these are difficult to measure accurately by diffraction methods on
crystals of large molecular structures due to the huge number of atoms to be located and
thermal motion and disorder in the crystal.
The purpose of this project is design a series of small molecules which will show a range
of such n-π* interactions and to measure their structures in the crystalline state and in
particular the O···C interaction by X-ray crystallography. The nucleophilicity of the donor
group will be varied from carboxylate anion to amides to ketone, while the electrophilicity
of the acceptor group will be varied from aldehyde, to ketone to amide. For the shortest
interactions, very accurate X-ray diffraction measurements will be made and interpreted
using Bader’s “Atoms in Molecules” approach to determine how the electron densities of
the two groups are distorted by the interaction, and thus provide a fundamental
understanding of this newly recognised interaction. The studies will be supported by
complementary high level quantum mechanical calculations, as applied in density
functional theory (DFT) using GAUSSIAN 09, to determine the relative energies of the
interactions as the electrophilicity and nucleophilicites of the groups are varied. This
project will provide a sound basis for the understanding of these interactions, and their
effects on the structures of polymers and polypeptides. Particular developments will be (a)
to design a small polypeptide and a lactide oligomer for study of this interaction as models
for polymeric systems and (b) to extend the study to the partial bonding between
oxyanions and related electrophilic multiple bonds.
The project is supervised by Prof John Wallis who has a wide experience in structural
organic chemistry, in particular of interactions and bonding between functional groups. Ab
initio calculations will be supervised by Dr Warren Cross and the polypeptide chemistry by
Prof Carole Perry both of whom are expert in these fields.
References
1 G.J. Bartlett, R.W. Newberry, B. VanVeller, R.T. Raines, D.N. Woolfson, J. Amer. Chem.
Soc., 2013, 135, 18682-18688; A. Choudhary, C.G. Fry, K.J. Kamer, R.T. Raines, Chem.
Commun., 2013, 49, 8166-8168; R.W. Newberry, R.T. Raines, Chem. Commun., 2013,
49, 7699-7701; A. Choudhary, K.J. Kamer, R.T. Raines, J. Org. Chem., 2011, 76, 79337937.
Specific qualifications/subject areas required of the applicants for this project:
1st or 2:1 M.Chem. in Chemistry or Crystallography.
For informal discussion regarding the project, please contact:
[email protected]