Operating Department Practice (ODP) and Paramedic Science students inspecting a box of prescriptions

Current research projects

Studying our Master of Research (MRes) Science allows you to focus your research interests on one or two areas of science and work towards translating your learning into research related outputs – such as a submission for a peer-reviewed publication; a peer reviewed research/knowledge transfer grant application, or a presentation.

MRes Science can be studied either full time (1-year) or part time (2-years). You will develop a wide variety of skills, experience and competence on this course, and the MRes will provide a thorough grounding for students moving towards Doctoral (PhD) studies, or pursuing research related activities as a career.

Please note this list of projects is not exhaustive and you'll need to meet and discuss the project you're interested in with a member of research staff before you apply.

MRes Science - Pharmacy and Biomedical Science research projects:

Mechanisms of diabetic peripheral neuropathy

Supervisor: Dr. Bennett Au

Diabetic peripheral neuropathy is one of the most common complications affecting more than half of the diabetic patients worldwide. Patients with diabetic peripheral neuropathy display a wide range of symptoms including numbness, tingling, burning/stabbing pain, muscle cramps and weakness. However, the mechanisms underlying this neurodegenerative disorder remained poorly understood.

Using a multidisciplinary approach spanning from multi-omics analysis, primary neuronal cultures, fluorescence/confocal microscopy, and immunohistochemistry, we aim to identify factor(s) that lead to axonal degeneration of primary afferent sensory fibres and the development of painful diabetic peripheral neuropathy in a mouse model of type 1 diabetes. This project will pave the way towards the development of novel therapeutics that can prevent or slow down the pathogenesis of diabetic peripheral neuropathy in the patients.

Factors underlying with the age-associated regenerative decline

Supervisor: Dr. Bennett Au

Our peripheral nervous system (PNS) is capable of axon regeneration at an extremely slow rate (i.e. 1-2mm/day), and thus functional recovery after PNS injury is still feasible if the injured peripheral axons reach their original distal targets within a limited time window. However, with aging, the regenerative capacity dramatically declines, which often leads to permanent and irreversible disability and an adverse impact on patients' quality of life. Previous studies have demonstrated that impairment of Schwann cell activation and excessive infiltration of T cells towards the peripheral dorsal root ganglion (DRG) neurons underlay this age-dependent regeneration failure. However, the factors that govern these age-related phenotyping switches of glial cells remained largely unknown.

Using a multidisciplinary approach spanning from primary neuronal cultures, fluorescence/confocal microscopy, immunohistochemistry and multi-omics analysis, we aim to identify factor(s) that cause the impaired dedifferentiation and activation of Schwann cells, and uncontrolled immune responses after peripheral nerve injury (PNI) in aged mice. The outcome of the current study will provide a more comprehensive understanding of the age-associated changes in the PNS that lead to development of novel therapeutic interventions to improve the functional outcomes after PNI.

Role of Eph/Ephrin Signalling in Neural Tube Closure

Supervisor: Jordi Cayuso

Neurulation is the process that leads to the formation of a hollow neural tube, which is the precursor of the central nervous system. During neurulation, neural tissue undergoes complex rearrangements and deformations due to intrinsic and extrinsic mechanical forces. Failure of the neural tube tissue to complete neurulation causes neural tube defects (NTDs), which constitute some of the more common birth defects and can lead to perinatal mortality and long-term disability. While the processes controlling neurulation have been extensively described at the tissue scale, the molecular mechanisms driving these changes and the causes behind NTDs remain relatively unknown.

Eph mutations have been identified in humans and animal models with NTDs, however, the way Eph signaling is involved in this process has not been investigated. Thus, using a combination of molecular cloning, immunohistochemistry, confocal imaging and image analysis in chicken and zebrafish embryos we will investigate how Eph signaling regulates the formation of the central nervous system.

Mechanisms of Fin Regeneration in Zebrafish

Supervisor: Jordi Cayuso

One of the aims of regenerative medicine is to design strategies that will enable us to repair damaged human tissues so that they can regain their function. Unfortunately, most human tissues have lost the capacity to regenerate and thus, they do not recover their functionality after injury or disease, e.g., spinal cord injury or cardiac infarction. In contrast, the zebrafish have the ability to regenerate most tissues, including the brain, limbs and heart. In this project, we will harness this extraordinary ability of zebrafish to understand the mechanisms of tissue regeneration.

The Eph/Ephrin signalling system is an important pathway that mediates communication between cells and is key for the formation of the nervous system, maintenance of stem cell pools and the formation of boundaries between tissues. We recently identified that Eph/Ephrin signalling is also critical for the regeneration of several tissues, including the caudal fin in zebrafish. Using this system as a model of study, we aim to obtain a better understanding of the processes that lead to successful tissue regeneration and to identify how Eph/Ephrin signalling directs these processes. This will be achieved through the analysis of the regenerating fin at the cellular and molecular level using a combination of wound healing, inflammation and growth markers and techniques such as gene knockdown, confocal microscopy, immunohistochemistry and data analysis.

The outcomes of this study will lead to a better understanding of the fundamental processes involved in tissue regeneration and will contribute to identify new strategies to improve regenerative outcomes in humans.

Screening Environmental Microbes for PET Degradation Capabilities

Supervisors: Dr Sam Robson and Prof Joy Watts

Accumulation of plastics in the environment is one of the major global challenges facing us today. Natural enzymes, such as those produced by micro-organisms (e.g., bacteria), may hold the key to breaking down plastics, with the potential to be deployed on an industrial scale.

The Centre for Enzyme Innovation (CEI) at the University of Portsmouth aims to identify and exploit such enzymes from the environment. They have developed a biobank of environmental samples collected from a range of sources, with potential for plastic-degrading enzymes to be present (waste sites, recycling plants, fuel tanks, sea sponges, etc.). The successful candidate will explore these samples to identify and characterise potential enzyme targets of interest for further research, and potential use for industrial deployment in the future.

In this project, you'll first select bacterial isolates of interest from the CEI biobank, culture these isolates, and perform DNA extraction in order to carry out PCR screening for known PET-degrading genes. Any isolates indicating a positive result from this PCR screening will then undergo confirmatory tests using microbiological techniques developed within the CEI (including screening using Coomassie blue staining of M9 agar and 5% PEG), as well as a novel technique developed by Charnock, 2021.

During this screening project, you'll undergo whole genome sequencing and RNA sequencing, providing the successful candidate with experience of Nanopore sequencing, bioinformatics analysis, and data exploration (e.g. de novo genome assembly, gene annotation).

Machine learning-based prediction of i-motif structures from Nanopore sequencing signal data

Supervisors: Dr Sam Robson, Dr Daniela Lopes Cardoso, Dr Garry Scarlett and Dr Fiona Myers

The aim of this project is to identify novel methods for the detection of non-standard 4-stranded ‘i-motif’ DNA structures from commonly used biophysical assays. In particular, this project will combine biophysics and genomics with machine learning approaches, to develop cutting-edge approaches for the high-throughput identification of these structures. As we understand more about the role that such structures play in metabolism and cellular function, such advanced approaches will be necessary to accurately distinguish i-motif from B-form DNA.

The i-motif is a non-standard DNA structure, very different to the typical Watson-Crick double-helix shape. The currently accepted sequence-specific definition of an i-motif over-estimates the number and misses potential i-motif forming sequences that do not follow the standard precisely. In particular, work by our collaborator Dr John Brazier has shown that the loops present in the 4-stranded structure are of great importance in the structure formation. It was previously believed that the i-motif structure was not biologically relevant and would not be seen under normal physiological conditions. However, recent evidence has directly visualised i-motif structures in the genomes of living cells under such cellular conditions. This, along with other recent evidence, strongly suggests that i-motifs play a currently under-explored role in molecular function and genomic regulation.

We have recently studied the effect of i-motifs on helicase enzymes, which act to unwind DNA during replication and translation. By using Oxford Nanopore Technologies (ONT) flow cells as real time helicase models, we have shown that helicase activity is affected by the secondary structure of i-motifs, resulting in a change to the translocation speed through the nanopore and effects at the raw signal transduction level. The successful candidate will further explore this effect and help to develop machine learning models for the prediction of i-motif structures from nanopore sequencing data.

This project will provide a powerful toolkit for identification of i-motif structures, and will link with further work within the group. This work will help in understanding the role that i-motifs play in development and disease, leading to a greater understanding of the complex machinery underpinning gene regulation, and the identification of novel targets for small molecule therapeutics.

Nanopore sequencing of cell-free DNA for early identification of prosthetic joint infection (PJI)

Supervisors: Dr Sam Robson and Dr Sharon Glaysher

Prosthetic joint infection (PJI) represents one of the most common reasons for failure among hip and knee arthroplasty, with an incidence of around 1-2%. Infection can occur early (within days of surgery) or late (over a year after surgery), and no specific early markers for infection onset exist. Given the significant costs to the NHS for corrective revision surgery, the added suffering and risks to patients from surgery, and the risk of enhancing antimicrobial resistance through the use of broad-spectrum antibiotics, a more specific predictive test for early onset of infection is required.

Over 80% of human infection is estimated to be a result of biofilm formation. Biofilms are an accumulation of microorganisms on a surface, resulting in a functional community which provides antibiotic resistance and a beneficial environment for the growth of pathogenic species that would otherwise be removed by the body’s defences. Biofilms can rupture, allowing pathogens to spread infection. To date, biofilm development and diversity on periprosthetic implants is poorly understood. It is not known whether biofilms associated with PJI differ from those in infection-free patients, or whether characteristic biofilms are associated with providing a microenvironment suitable for PJI-associated pathogens to thrive.

In this project, you'll explore the possibility of early detection of PJI from cell free DNA from blood samples collected from individuals who have undergone hip joint prosthetic replacement. This data will link to a wider-scale data set exploring the characteristic microbiome of hip joint prosthetic biofilms. This has the possibility of providing a relatively non-invasive diagnostic tool for PJI detection, with potential benefits for many.

Immunomodulatory potential of bacterial exosomes

Supervisor: Dr Murphy Wan

Bacterial exosomes are extracellular vesicles that are secreted by Gram-positive and Gram-negative bacteria. They contain a wide range of molecules, including proteins, lipids, and nucleic acids. In recent years, several studies have shown that bacterial exosomes play an important role in intercellular communication, host-pathogen interactions, and immune modulation.

In particular, bacterial exosomes have been shown to have an immunomodulatory effect on host immune cells. They can suppress or activate immune responses depending on the type of bacteria and the host's immune status. For example, some bacterial exosomes have been shown to inhibit T-cell proliferation and induce regulatory T cells, while others can activate macrophages and dendritic cells.

Understanding the mechanisms behind the immunomodulatory effect of bacterial exosomes is crucial for the development of new therapies for infectious and autoimmune diseases. Therefore, the aim of our research is to investigate the mechanisms underlying the immunomodulatory effect of bacterial exosomes.

Development of targeted therapy for colon cancer

Supervisor: Dr Murphy Wan

Globally, colorectal cancer (CRC) is one of the top most commonly diagnosed cancers according to the World Health Organisation. The global burden of CRC is expected to increase by 60% to more than 2.2 million new cases and 1.1 million deaths by 2030. Current management of CRC include the use of chemotherapy drugs, such as fluorouracil or irinotecan, and radiotherapy. However, these standard treatments often incur high cost and cause various side effects and organ toxicities resulting in a lower quality of life for patients. As such, there is an urgent need to develop less costly alternatives to chemotherapy.

This project will focus on discovery of novel therapies for cancer, which involves the design of colon-targeted delivery system and evaluation of the anti-cancer potential of the novel drug system through the uses of different analytical, cellular and molecular techniques in experimental models – including cell culture and in vivo models. This is a multidisciplinary project involves collaboration and interaction with experts from other fields. You'll receive training in all relevant areas, but not limited to analytical chemistry, nutrition, molecular biology, immunology, toxicology, with an emphasis on integration of different omics technologies for in-depth investigation of disease mechanisms and discoveries of novel biomarkers that can be translated in future clinical settings.

Early cancer diagnosis with unique Raman spectroscopic solutions for cancer biomarker and/or location detection

Supervisor: Dr Priyanka Dey

It's estimated that 1 in 3 cancer deaths could be prevented if detected early – when treatment is more effective. Traditional tissue biopsies, or the new-era cancer imaging technologies, are unable to provide the vital early diagnosis that can make the difference in prognosis. In contrast, the detection of biomarkers, which are disease-specific biological molecules found in the body, provides one of the best ways, in principle, to detect cancers at an earlier stage. For example, prostate-specific antigen (PSA) was proposed as a biomarker in the 1980s. Although it's still used clinically, its prediction accuracy or specificity for prostate cancer diagnosis is debatable. Therefore, multiple biomarkers must be identified from specific cancer cell lines, which when detected simultaneously, could help diagnose the specific cancer types early. The project will explore the bioanalytical technique of Raman spectroscopy as a non-staining, non-histopathological, fast method to detect subtle changes in the chemical structures of the biomarkers-of-interest. This can aid in biomarker screening and lead to accurate diagnosis with high cancer specificity and progression monitoring capabilities.

Investigating mechanisms of mitochondrial and nuclear genome stability

Supervisor: Dr Robert Baldock

Defects in cellular DNA repair mechanisms are associated with numerous human diseases, including cancer. The absence of these key pathways leads to increased genomic instability and altered cellular function. Research has identified a number of DNA repair proteins that protect nuclear DNA, they're also localised in mitochondria – although their functional role remains unclear. This MRes project will help characterise the role of these proteins in protecting the mitochondrial and nuclear genomes, as well as identifying their potential role in disease progression. You'll gain experience in a number of molecular biology and cell biology techniques and use bioinformatic approaches to generate and test novel insights.

Optimisation of lipid nanoparticles (LNPs) for targeted gene delivery to cancer cells

Supervisor: Dr Roja Hadianamrei

Pharmaceutical and biomedical research is shifting towards using biological drugs (peptides, proteins, nucleic acids) instead of small molecule drugs for treatment of a wide range of diseases including infectious diseases, endocrine and metabolic disorders, neurodegenerative diseases, and most notably cancer. Despite great advances in the field, there is still so much room for research to fill in the gaps and optimise current practices. This project is aimed at developing lipid nanoparticles (LNPs) with optimised physicochemical properties for the delivery of small interfering RNA (siRNA) to cancer cells. It's an interdisciplinary project combining pharmaceutical science, nanomedicine, molecular and cell biology.

siRNA are synthetic noncoding RNA which are capable of silencing selected genes in order to down regulate the unwanted proteins. LNPs are the new generation of non-viral gene vectors which have gained increasing attention in the last few years due to their successful application in mRNA based Covid vaccines. Applications of siRNA encapsulated in LNPs for gene therapy is a new promising approach in the treatment of metabolic diseases and cancer. The first FDA approved siRNA drug, Patisiran (ONPATTRO), consisting of siRNA encapsulated in LNPs, has entered the market in the USA and EU in 2019.

Building on my previous research in development of siRNA-based therapeutics for cancer and metabolic disorders using LNPs, and peptides in academia and pharmaceutical industry, I'm now working on the development of new LNP formulations for the targeted delivery of new types of siRNA to cancer cells. In this project, a new library of LNPs will be generated using microfluidics. The effect of formulation and process parameters on the physicochemical properties of the LNPs will be studied using design of experiment (DOE) approach. The LNPs with optimised physicochemical properties will then be tested for their ability to deliver siRNA to cancer cells and induce gene silencing. Working on this project will provide you with knowledge and practical skills in DOE, preparation of LNPs using microfluidics, analytical techniques (such as DLS, GE, UV and fluorescence spectroscopy), cell culture and cellular assays (transfection and gene silencing).

Modified triplex-forming oligonucleotides as therapeutic agents

Supervisor: Dr David Rusling

Oligonucleotides are short synthetic strands of DNA or RNA that can be used to treat or manage a wide range of diseases, for example by silencing specific genes. In recent years, various oligonucleotides have made it through clinical trials and have now reached the clinic to some fanfare. They often elicit their affects via antisense or RNAi mechanisms by acting on messenger RNA molecules and modulating protein expression inside living cells. Although this has been hugely successful, a better strategy, at least in principle, would be to use oligonucleotides to target genomic DNA directly and prevent messenger RNA expression altogether. Oligonucleotides that might prove useful in this manner are known as triplex-forming oligonucleotides, on account of their binding to specific duplex sequences and generating a triplex structure.

Our research group has recently overcome a long-standing problem associated with these molecules using oligonucleotides containing modified DNA bases. We are now at the stage of developing these molecules as gene-targeting agents and this MRes project will help us in attaining that goal. The student will gain experience in a wide variety of biochemical, biophysical and biological techniques used to characterise the formation of triplex DNA, and the project will involve a large amount of assay design and optimisation.

Targeted delivery of large macromolecular cargoes to subcellular environments

Supervisor: Dr Bruce R Lichtenstein

One of the grand challenges in biology is the targeted delivery of macromolecular complexes to specific sites in eukaryotic cells.

Recent mRNA vaccines highlight the potential of delivered macromolecules to effect physiological changes in organisms, but we still remain quite distant from our goal of making selective changes to cellular physiology down to the organelle level. To meet this challenge, extracellular macromolecules must be delivered to sites of interest within selected eukaryotic cells. Our recent work with engineering AB5 toxins highlights the flexibility of these carriers to transport cargoes of unconstrained identity into eukaryotic cells.

This project will define the limits of the delivery system towards applications in targeted therapies and cell engineering, by examining the delivery of supramolecular protein assemblies targeted to different subcellular environments. This research project would suit a biology, biochemistry, or biomedical student with interest in molecular biology, protein engineering, tissue culture, and confocal or super-resolution microscopy.

 

A drug-screening approach to understand the formation of the brain's perineural vascular plexus

Supervisor: Dr Susanne Dietrich

The formation of the peri-neural vascular plexus (PNVP) is the first step in the development of the brain's vascular network, which is crucial for the correct development and function of the brain. The precursor cells are thought to originate from multipotent precursor cells in the head mesoderm. Yet how these cells are mobilised to become vascular endothelial cells that assemble around the developing brain is not known. The student will screen pharmaceutical drugs for their effect on PNVP formation in the frog embryo, using a semi-automated platform. The student will then verify drugs and affected molecular pathways using drug-loaded carrier beads in the chicken embryo. The work will pave the way towards an understanding which signalling pathways are crucial to initiate the vascularisation of the brain.

Cell fate choices of cardiopharyngeal precursor/stem cells

Supervisor: Dr Susanne Dietrich

Cardiopharyngeal precursor/stem cells are a subpopulation of cells in the head mesoderm. The cells have the choice to become a heart muscle or a craniofacial skeletal muscle cell, and errors in their decision making can lead to significant birth defects. Our lab has identified candidate genes that may regulate the allocation of cells to either the cardiac or skeletal muscle programme. The project will explore the role of these genes, using gene misexpression and gene knockout/knockdown approaches in the chicken embryo. The work will contribute to the knowledge and understanding needed to generate defined precursor/ stem cells for example for cardiac therapy.

Protection of the stem cell state of embryonic muscle stem cells

Supervisor: Dr Susanne Dietrich

Adult muscle stem cells repair skeletal muscle after mild forms of injury. Yet when cultured in vitro to rebuild muscle of patients suffering from muscle loss by severe accidents or muscle disease, these cells lose their stem cell properties as well as their ability to generate muscle. The embryonic version of the adult muscle stem cells seems to be able to retain stem cell features and myogenic capacity. The project will use gene misexpression approaches to challenge embryonic muscle stem cells in the chicken embryo model, and to explore how the stem cell protective mechanism works. The work will contribute to the knowledge and understanding needed to generate muscle stem cells better suited for therapy.

Social prescribing services - an appraisal of their evaluation

Supervisor: Dr. Nicola Barnes

Social prescribing enables the referral of people to a variety of non-clinical services. People’s health and wellbeing is determined by a range of social, environmental and economic factors as well as their physical and mental health.

Social prescribing has been introduced to address people’s needs in a holistic way, encouraging them to take control of their health. Social prescribing can involve multiple activities, commonly provided by voluntary and community organisations, such as cookery, volunteering, exercise, art, gardening and group learning. Various models for delivering social prescribing have developed, usually involving a link worker or working with people to access the different services. The service models vary from working face to face with people over a long period to a very light touch approach that may involve a single telephone conversation. As such, there is unlikely to be a single evaluation tool that can effectively evaluate the impact of these different service models. T

his project aims to:

  • identify the range of services that could be described as social prescribing in the Portsmouth and Isle of Wight area, particularly those using a light touch approach
  • identify the psychosocial constructs, or socioeconomic issues that the services target
  • collect data on the methods currently used to evaluate these services
  • review the evaluation of such services in the UK by using the National Social Prescribing Network and appraise the evaluation methods currently in use
  • make recommendations on the future evaluation of such services

Effects of mechanical stimulation in the proliferation and differentiation of mesenchymal stem cells into the osteogenic lineage

Supervisor: Dr Marta Roldo

In the UK 300,000 bone fractures occur a year, mainly due to age related diseases such as osteoporosis. These have a great impact on patients’ quality of life and the NHS budget. Many of these fractures are complex and unable to self-heal. They can often be treated with implantation of bone from the patient, or using bone substitute materials. In both cases there are serious limitations to the success of the current treatment options. New strategies must be developed.

Scientific knowledge suggests that the most promising strategy is the development of novel materials. These should provide a support over which staminal cells can change into bone-forming cells, and moreover they should work as a platform for the controlled delivery of drugs. Furthermore, it is known that forces applied to bone fractures have a role in the repair process, so developing a material able to harness the positive effect of these forces is a promising strategy.

We have developed promising new materials - the aim of this study is to investigate the relationship between their chemical and physical characteristics and how their potential to induce bone repair is affected by the forces applied to them. This work will provide protocols and tools to better understand how we can exploit mechanical forces as a method to stimulate the bone to repair itself and how materials for bone repair can be combined with mechanical forces to result in highly effective and safe treatments for bone repair.

High-throughput discovery of novel antibiotics using synthetic microbiology

Supervisor: Dr Roger Draheim

Antimicrobial resistance (AMR) is a frequent problem in the treatment of disease caused by several clinical bacterial pathogens. In the European Union, antibiotic resistant infections kill nearly 25,000 patients and represent a total expenditure of £1.5 billion per year. In response, the Chief Medical Officer (CMO) of the United Kingdom termed antibiotic resistance “a major area of concern” and proposed its inclusion on the National Security Risk Assessment, which prioritises major disruptive risks to national security.

Furthermore, the CMO suggested that the UK government facilitate global action, especially concerning the development of novel antibiotics. However, given the expensive research, development and clinical testing required to bring an antibiotic to market, coupled with the fact that they are taken for limited time courses and not for life, makes them a very unattractive prospect for pharmaceutical companies.

This MRes project is responsible for implementation of a novel “biological antibiotic screening” platform. The overall aim of this project is to develop this screening technology in order to sharply reduce the economic cost required for antibiotic discovery to the point where it becomes adopted as the de facto standard within the pharmaceutical industry. This multidisciplinary project will be conducted within newly renovated laboratory space and spans a broad range of biological sciences including molecular biology, microbiology, biochemistry, high throughput screening and collection/management of large data sets (i.e. big data). Applicants will ideally have previous experience in one or more of these topics, although will receive training in all relevant areas.

In addition, students will have access to a vast number of training resources available at through the Graduate School including those geared toward improving presentation skills, time-management and project organisation skills, reviewing literature, thesis writing, data analysis and statistics, and other various related training modules.

State of the art correlative imaging application in the study of morphological and functional behaviour of chondrocytes cultured in traditional 2D culture versus 3D printed scaffolds 

Supervisor: Dr Marta Roldo

We offer an exciting opportunity for an MRes student to work in collaboration with scientists at the Diamond light source in Oxford.

Cartilage is an avascular tissue with poor nutrient infiltration and oxygen diffusion. These issues can hinder healing after injury or trauma. A particular problem in cartilage wound healing is the formation of fibrocartilage, which is functionally and biomechanically inferior to the native tissue. Current therapies to facilitate cartilage regeneration (e.g. autografting, microfractures and autologous chondrocyte implantation) having limited success in restoring functional tissue.

Cartilage tissue engineering (CTE), or the implantation of biocompatible scaffolds loaded with chondrocytes or stem cells, could be a turning point in the treatment of cartilage damage. A deep understanding of the interactions between cells and the biomaterials used for their delivery is key to the development of novel CTE therapies.

The aim of this project is to understand, through non-destructive high-resolution cryo x-ray tomography, correlative fluorescence microscopy and gene expression, the effect that the culture environment in a 3D scaffold has on the morphology and function of chondrocytes. Current cell culture practices and analytical techniques are limited providing a 2D environment for cell growth which results in a cell behaviour dissimilar from the in vivo realty. The state of the art facilities at Diamond, beamline B24, will allow the study of cells in a 3D environment that will be created by 3D printing of hydrogels with the newly acquired Bioprinter.

This project will provide the student with training in state of the art techniques uniquely available through the collaboration between the University and Diamond. The project is multidisciplinary and involves biology, physics, bioengineering and biomaterials, and will provide the student with a unique set of skills that are very competitive in the current job and research market.

This project will be co-supervised by: Prof Gordon Blunn, Dr Gialuca Tozzi and Dr Maria Harkiolaki (University of Oxford).

Functional and clinical significance of mito-genomic elements in brain tumours

Supervisor: Dr Rhiannon McGeehan

Glioblastoma is the most common and malignant primary brain tumour in adults, and is characterised by a dismal prognosis. Current prognostic and predictive markers, and treatments for glioblastoma that rely on nuclear DNA are inadequate. Consequently, we and others are turning to mitochondria, in particular their DNA (mitochondrial DNA, mtDNA) as a promising alternative. Mitochondria are impaired in glioblastoma, and we are identifying the underlying factors in their mtDNA that could be responsible, including how such factors contribute to malignant progression, chemoresistance, and ultimately patient survival.

To date, we have identified several novel mtDNA factors that are heterogeneously expressed between glioblastoma patients, and between glioblastoma patients and healthy controls. These mtDNA factors are either linked to cell behaviours, including mitochondrial-targeted drug sensitivity, in our glioblastoma models and/or are associated with survival in our glioblastoma patient cohorts.

Using a combination of bespoke bioinformatic approaches, mitochondrial and cellular behaviour assays, glioblastoma cell models, and in house and external patient databases, the goal of this MRes is to join our Mitochondria group within the UoP Brain Tumour Research Centre in order gain comprehensive insights into the functional and clinical significance of mtDNA features, and to identify and develop new prognostic and predictive markers, and drug targets.

The role of Tyro3 as an oncogenic receptor tyrosine kinase in cancer cells

Supervisor: Dr Sassan Hafizi

The TAM (Tyro3, Axl, Mer) subfamily of receptor tyrosine kinases (RTKs) regulate diverse physiological processes such as cell survival, tumour development, glial cell regeneration, and the immune response. The Hafizi lab investigates the mechanisms surrounding the ligand-receptor interaction and how it is altered in various diseases – for example several cancers, where the TAMs are found overexpressed and thereby drive tumour progression and spread. 

Tyro3 is the least characterised out of the three TAM RTKs, although it too has been detected as aberrantly expressed in a number of cancers, including melanoma and bladder carcinoma. The proposed MRes project is aimed at studying the molecular mechanisms behind the functions of Tyro3 RTK in cancer cells, with a view to distinguishing it from the roles of Axl and Mer. 

The project will be entirely carried out using human cancer cells in culture as an in vitro model to study cell biological functions and intracellular signalling. The effects of addition of TAM ligands on cells via Tyro3 will be determined through assays for measuring cell viability, proliferation, cell cycle progression, migration and invasion. Changes in expression/phosphorylation of key cancer-related intracellular signalling molecules will be detected by western blot and real-time qRT-PCR. In addition, Tyro3 overexpression and siRNA knockdown experiments will be carried out in cells to reveal the ligand-independent functions of Tyro3 in regulating cancer cell signalling. The project may also test a novel set of Tyro3 small molecule inhibitor compounds that we have identified. 

The results of this project should provide novel insights into the function of Tyro3 in promoting cancer, sufficient knowledge of which has been lacking for some time. Consequently, such knowledge will help determine whether Tyro3 will be a viable novel cancer therapeutic target.

TAM receptors as mediators of remyelination and repair in multiple sclerosis (MS)

Supervisor: Dr Sassan Hafizi

MS is a condition caused by damage to oligodendrocytes, the specialised myelin-forming glial cells in the CNS, thus impairing normal nerve electrical impulse transmission. However, the CNS contains stem cells, which could be activated to proliferate and form new oligodendrocytes as part of a repair response that produces new myelin insulation for damaged nerves. In addition, the immune system also plays a part in provoking the damage to myelin during the progression of MS. Therefore, understanding the mechanisms that drive oligodendrocyte regeneration as well as regulate the immune response in the brain could provide novel targets for MS therapy.

We are investigating the role of Gas6 as a novel regulator of myelination in the brain, both in terms of promoting remodelling/repair after damage as well as dampening the immune response to prevent further damage. In our experiments, we utilise a range of cell biological and biochemical techniques, including ex vivo brain tissue culture, in vitro cell culture, molecular expression analyses, immunohistochemistry, confocal microscopy, and genomic and proteomic analyses. The MRes project will be part of this research team effort, and the experiments will provide data that will add to our understanding of the potential beneficial role of Gas6 in remyelination in conditions such as MS.

Other Research Projects

Discover the current research projects available in each of our schools and departments: 

Please note, this list is not exhaustive and you'll need to meet and discuss the project you're interested in with a member of research staff before you apply.