SHSSW photo shoot, November 2018 Nursing, Operating Department Practice (ODP) and Paramedic Science students.

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:

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.

Galectin-3 as a novel ligand for TAM receptor tyrosine kinases

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. 

Alongside the well-known TAM ligands (Gas6 and ProS1), recently the sugar-binding lectin, galectin-3 (Gal-3) was reported to act as a novel TAM ligand, although with the role of stimulating the function of phagocytic cells. However, it is not yet known whether Gal-3, which is upregulated in many cancers, can exert pro-tumorigenic effects via the TAM receptors in cancer cells. Therefore, the aim of this project is to determine whether Gal-3 can stimulate one or more of the TAM receptors in human cancer cells in culture, and thereby promote growth, migration or invasion of the cells. Such effects will be studied to distinguish them from the effects of the other known TAM ligands. 

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 exogenous recombinant Gal-3 protein to cells 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. A synthetic Gal-3 inhibitor compound will be tested for its potential blocking effects in terms of specificity and potency. In addition, siRNA knockdown experiments will reveal the role of endogenous Gal-3 in cancer cells. Also, a biochemical and/or site-directed mutagenesis approach will also be taken, if time permits, to probe the interaction between Gal-3 and the TAM receptor via the glycosyl chain that is present on the extracellular part of the TAM receptor. 

The results of this study should provide an insight into whether Gal-3 is a novel TAM ligand, pro-tumorigenic molecule and therefore a potential cancer therapeutic target.

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.