EPSRC DTP PROJECTS - UNIVERSITY OF GLASGOW
Below you will find an exciting and diverse range of available 19/20 EPSRC DTP studentship projects.
Developing an information-theoretic predictive factor analysis method with application to multi-modal neuroimaging datasets of aging in health and disease
While there are many successful applications of machine learning techniques to clinical and epidemiological data sets, these tend to focus on prediction performance at the expense of scientific understanding. This project will develop a method based on information theory to obtain predictive factors each consisting of a set of multi-model predictor variables (e.g. anatomical or functional neuroimaging features, behavioural and psychometric test scores) which provide a common influence on an outcome (e.g. a diagnosis, or a behavioural index of cognitive decline). This method will be developed using the Cam-CAN dataset (650 healthy people) and then applied to a different dataset which includes participants with various age-related cognitive diagnoses. The obtained predictive factors will link brain structure (quantified with anatomical MRI), brain function (quantified with M/EEG and fMRI of the brain at rest and engaged in tasks), and behaviour (assessed with tasks performance and psychometric questionnaires). Relating these three aspects is a fundamental issue in cognitive neuroscience, and the predictive factors will show which specific neuroimaging features underly which behavioural deficits during aging in health and disease. The developed method for obtaining predictive factors will also be applicable to a wide range of different machine learning and data science problems.
Development of nanoparticle-based platforms for the control of vascular inflammation
Atherosclerosis comprises progressive occlusion of arteries, via plaque formation, leading ultimately to myocardial infarction and stroke. Immune responses play a critical role in atheroma development; however, immunomodulatory therapies are not used routinely to treat atherosclerosis, reflecting in part, concerns about systemic immune suppression given the necessity for chronic therapeutics. Nanotechnology can potentially deliver drugs selectively to atherosclerotic plaques avoiding systemic exposure. Recently, high-density lipoproteins, natural nanoparticles that transport cholesterol to the liver, have been used for targeted drug delivery to atheroma. Herein we will employ a novel microfluidics-based method to produce lipoprotein mimicking nanoparticle carrier vehicles to selectively deliver immunomodulatory drugs to atheromatous plaques. We will incorporate appropriate detection moieties e.g. fluorochromes into nanoparticles, to enable their localisation by various imaging modalities. Thereafter, we will evaluate the anti-inflammatory impact of locally delivered immunomodulators in vitro in complex vascular cell culture and in vivo in validated murine models of atherosclerosis.
Doubly caged effectors for spatiotemporal control of protein expression in vivo
Approaches to investigate the molecular basis of cell function in vivo are limited by a lack of spatial and temporal control of gene expression. This project aims to develop a technology that will provide a step change in unravelling these complex mechanisms in vivo. This will be achieved by developing chemistry and optogenetics for spatiotemporal control of gene expression in intact living mice. Thus, the technology will allow researchers to reveal where and when a gene contributes to cellular processes in vivo. This project will focus on immune homeostasis and inflammatory disease, however this approach will have applications in a wide range of biomedical disciplines.
High performance modelling of global plant biodiversity
A key goal of the Aichi biodiversity targets set out by the Convention on Biological Diversity is to ensure the conservation of biodiversity by providing necessary ecosystem services sustainably. Plants are fundamental to the provision of these ecosystem services, yet existing modelling approaches focus on just a few, broad plant functional types. Such approaches provide powerful insights into large-scale ecological processes but struggles to capture the effects of climate change due to assumptions about the uniformity of behaviour of large classes of species with differing niche preferences.
Researchers at the Boyd Orr Centre for Population and Ecosystem Health have developed finer resolution simulation models of global plant biodiversity to better characterise the effects of this variability within these functional types. Our EPSRC-funded PhD student will work with this team to predict how plant biodiversity will respond to future climate change scenarios predicted by the latest climate models, and to better understand how well the data currently being gathered to assess changes in biodiversity will be able to detect these impacts.
Applicants should be quantitative ecology graduates with a strong interest in deepening their computational, mathematical and statistical skills, or computer scientists, mathematicians or statisticians determined to develop their skills to address practical issues around the global impact of climate change.
The studentship will be based in the award-winning Boyd Orr Centre for Population and Ecosystem Health – http://www.gla.ac.uk/boydorr – and the Institute of Biodiversity, Animal Heath and Comparative Medicine – http://www.gla.ac.uk/bahcm . Please get in touch with Richard Reeve – http://www.gla.ac.uk/people/richardreeve – if you have any questions about the project.
Novel Molecular Probes for Subcellular Quantification of NO in Whole Organisms
Nitric oxide is a free radical gas. It has protean signalling functions in many organs during normal physiology and in disease states. Reduced vascular NO production causes hypertension and is an established cardiovascular risk factor. In contrast, high level NO production in macrophages or cardiovascular cell types contributes to the inflammation seen in atherosclerosis. Recent work by Schiattarella et. al. implicates NO in both the establishment and progression of heart failure. In an acute setting it also drives the hypotension in sepsis. NO has a very short half-life in vivo (t1/2~1.5s). Its concentration in different subcellular localities has been impossible to determine in whole living organisms. This project aims to use an exomarker strategy to solve this problem. Novel molecular probes (low molecular weight chemicals) will be designed, synthesised and fully characterized. They will detect NO through specific chemical reactivity to give NO-diagnostic products (exomarkers). LC-MS methods will be developed for accurate quantification. Each molecular probe will target a different sub-cellular compartment. Their localization and ability to detect NO will be validated in cells, and they will then be used in whole organisms by other researchers in the group. Potential therapeutics that modulate NO will also be developed.
Parallel-transmit MRI techniques for clinical neuroimaging at 7 tesla
Ultra-high-field magnetic resonance imaging (MRI) at 7 tesla (T) provides medical images with a high spatial resolution compared to existing diagnostic scanners, operating at 3T and 1.5T. Recently, 7T MRI was approved for medical use in Europe and the USA and there is strong worldwide interest in its application to clinical neuroimaging. However, MRI at high field strength is confounded by the reduced electromagnetic wavelength in human tissue, which causes poor image uniformity and limits reliable diagnosis. Preliminary work has shown that this issue can be addressed by parallel-transmit techniques, which use an array of independent RF transmitters to control the data-acquisition process. However, these techniques are not yet in routine use and further development work is required, which is the subject of the proposed PhD project. The successful candidate will use a mixture of computer simulation and experimental measurements to identify optimum parallel-transmit acquisition schemes for a range of clinical conditions in the brain and spinal cord. The project would suit a graduate in physics, engineering or applied mathematics and will be conducted in the Imaging Centre of Excellence (ICE) on the Queen Elizabeth University Hospital campus as part of a multi-disciplinary team of scientists, engineers and clinical researchers.
Protac Antivirals – An Innate Immune-Guided Chemical Biology Approach
We are seeking to recruit a PhD candidate in chemical biology / molecular virology for October 2019. This project involves collaboration between the Centre for Virus Research and School of Chemistry at the University of Glasgow, looking at a new potential strategy for treating viral infection. Our approach is based on selective degradation of viral proteins, rather than more conventional inhibition-based paradigm. The successful applicant for this multidisciplinary project will first carry out the synthesis of a new set of compounds, followed by carrying out biological assays to gauge efficacy. We will initially probe our new anti-viral strategy in the context of the well characterised HIV-1 virus, but extension to less studied pathogens like Zika and Ebola is a long term ambition.
The Design, Synthesis and Application of Reporter Probes for Methionine Oxidation Targeted to Specific Intracellular Compartments
Oxidation of proteins leads to their inactivation and results in diseases such as Alzheimer’s and Parkinson’s. Mammalian cells contain poorly characterised enzymes called methionine sulfoxide reductases that are able to reverse the oxidation of methionine and protect proteins from oxidative damage. As the overexpression of these enzymes increases cellular resistance to oxidative stress, it is highly likely to act as an antioxidant during normal physiology and during specific diseases and ageing. Most recently, we have shown that these enzymes can act as oxidases as well as reductases. This discovery opens up the possibility that the enzyme can reversibly modify substrates indicating a role in regulation of protein function. This project will further our understanding of the role of methionine oxidation in cellular function. We will design novel chemical probes that can be used to monitor the extent of methionine oxidation in different cellular compartment with both spatial and temporal resolution. The project will require probe design and synthesis, live cell imaging and molecular cell biology techniques to determine the role of methionine sulfoxide reductases in cell physiology. The project is a collaboration between a cell biology and chemistry laboratory enabling the student to obtain training in the burgeoning field of chemical biology.
(TARDIS) Towards Augmented Reality in rehabilitation for those with neuro-DISability
Assistive technologies help compensate for cognitive difficulties after neurological impairment, allowing people with these impairments to maintain their independence and social participation. We propose that augmented reality (AR), which superimposes virtual objects into the physical environment in real time, is a powerful solution to providing support in real world settings. The augmented and virtual reality healthcare market is expected to reach $5.1 billion dollars by 2025. However, only limited research has been completed using these technologies as interventions to assist users with cognitive impairment. This is a significant missing piece, considering that by 2030, around 387 million people worldwide (4.9% of the estimated population) will have a neurological impairment from acquired brain injury, stroke or degenerative disease.