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Find out more about self-funded PhD projects in areas of biomedical science.
We already have supervisors active and engaged in the research topic in our School of Life Sciences.
Efficient and accurate DNA repair is essential for the maintenance of genome stability. Failure to repair DNA accurately can result in cell cycle arrest, apoptosis and at the organismal level, the development of cancer. Sophisticated, multi-protein DNA repair systems in human and eukaryotic cells repair a wide variety of DNA damages generated as a result of exposure to environmental carcinogens and mutagenic compounds generated internally as a result of normal metabolism (Kryston et al., 2011).
Over the past two decades a significant investigative effort has delineated the fundamental mechanisms of DNA repair in human and eukaryotic cells. To date some 150 DNA repair genes have been identified. Importantly, there are a number of rare genetic diseases where an inherited mutation of one or more of the genes involved in DNA repair render the individual hypersensitive to DNA damaging agents and dramatically increased cancer incidence (Wood et a., 2001).
DNA repair capacity also has fundamental implications in the treatment of cancer. The majority of anticancer treatments rely on the ability to introduce DNA damage in cancer cells to bring about cell death. Therefore the DNA repair capacity of cancer cells will have a major impact on the ability to cure a cancer with chemotherapy or radiotherapy (standard methods of treatment). In fact a major driver in the pharmaceutical industry is to target DNA repair pathways for inhibition in order to cure cancer.
An exemplar of the above phenomenon is displayed in the treatment of ovarian cancer (OC) where there are some 7000 cases per year in the UK. The clinical management of OC is challenging with 35% overall 5 year survival rates (Cancer Research UK). A major contributing factor to poor clinical outcomes in OC is the development of resistance to anticancer therapy where enhanced expression of key DNA repair proteins has been demonstrated. While this observation is extremely important most investigations in to DNA repair gene expression in OC have been limited in scope focusing on a single DNA repair gene or pathway (Adam-Zahir, 2014).
The advent of post-genomic technologies has led to the establishment of large genome data repositories freely available to the scientific community. We are now in a position to analyse the expression of the entire complement of DNA repair genes ('the human DNA repairome') in cancer and normal tissue from the same individual (Peng et al., 2015).
The PhD research project hypothesis is that enhancement of DNA repair causes drug resistance in ovarian and other cancers. We will use bioinformatics approaches to determine the expression levels of the entire human repairome in drug resistant cancer.
The aims in Year 1 will be to interrogate The Cancer Genome Atlas (TCGA) and identify RNAseq data sets (the level of expressed genes in the human genome) for ovarian cancer and matched normal tissue.
Year 2 will involve developing an intelligent solution using artificial intelligence (AI) algorithms, particularly machine learning to determine the level of gene expression of all 150 DNA repair genes in:
Year 3 will be to:
Taking the research forward, common patterns of DNA repairome expression in cancer will guide the development of novel drugs designed to inhibit DNA repair pathways in cancer cells and lead to innovative methods for the treatment of cancer.
This project is self-funded.
Details of studentships for which funding is available are selected by a competitive process and are advertised on our jobs website as they become available.
If you wish to be considered for this project, you will need to apply for our Biomedical Science PhD. In the section of the application form entitled 'Outline research proposal', please quote the above title and include a research proposal.
Transglutaminase 2 is an enzyme that cross-links proteins inside cells and contributes to cellular adhesion in tissues. Our group is interested in its many roles that can tip the balance between cellular proliferation and cell death. Our group’s research projects are currently investigating:
The current work involves a wide range of molecular and biophysical techniques including: immunohistological analysis of transglutaminase 2 in human breast cancer biopsy samples; tissue culture of human cancer cell lines; analysis of TG2 expression in response to drug therapy by cell toxicology assay, membrane purification and analysis, Western blot analysis, confocal microscopy and flow cytometry; RT-PCR analysis of mRNA, SiRNA (silencing) knockdown of mRNA; inductively coupled plasma atomic emission spectroscopy for measurement of cellular uptake of platinum based drugs.
Other specialist biophysical methodologies will be developed as part of these projects – particularly project 4.
Expected outcomes are:
This project is self-funded.
Details of studentships for which funding is available are selected by a competitive process and are advertised on our jobs website as they become available.
If you wish to be considered for this project, you will need to apply for our Biomedical Science PhD. In the section of the application form entitled 'Outline research proposal', please quote the above title and include a research proposal.
Cardiovascular, Translational Biomedicine
Background: Macrophages play a critical role in homeostasis and diseases. They can change their phenotype to perform differential activities in different phases of inflammatory response.
Polarized macrophages are broadly classified into two groups:
It has been demonstrated that M1/M2 switch plays critical role in inflammation which is dependent on various factors such as bioavailability of different subsets of monocytes and macrophages, sequential monocytes recruitment into the tissue in the process of inflammation or response to different conditions. Furthermore, the misbalance of M1/M2 switch can lead to chronic inflammatory diseases. Undoubtedly the generation of novel anti-inflammatory drugs regulating M1/M2 switch is an important step for pharmacological intervention of chronic inflammatory-based diseases. Unfortunately, the current drug screening strategies are not based on macrophage polarization. The development of a phenotypic macrophage high-throughput assay will provide a platform for screening of pro or anti-inflammatory properties of the candidate molecule (preclinical drug validation) or FDA approved drugs library and selected compound libraries with known anti-inflammatory activity (clinical drug validation).
Main goal and objectives: The main goal of the study is to develop and validate a novel phenotypic macrophage high-throughput cell-based assay for anti-inflammatory drug screening activity. The two main objectives are:
Methodology: Cell culture and cell-based essays, western blotting, ELISA approaches.
Collaborations: This project is based on academic and industrial collaborations with Reading University and Innaxon, UK respectively.
Outcomes: Results from this project will evaluate the potential of the phenotypic macrophage high-throughput assay for drug screening as well as provide important information about the effect of the candidate molecules on macrophage polarisation and will contribute to their preclinical/clinical validation. This will represent a finding of great public and commercial impact as currently there are no macrophage cell-based phenotypic assays for drug screening. The proposed project will have a commercial value and we plan to secure protection of the arising intellectual property.
This project is self-funded.
Details of studentships for which funding is available are selected by a competitive process and are advertised on our jobs website as they become available.
If you wish to be considered for this project, you will need to apply for our Biomedical Science PhD. In the section of the application form entitled 'Outline research proposal', please quote the above title and include a research proposal.
Cardiovascular, Translational Biomedicine
Background: Toll-like receptors (TLRs) serve as pattern recognition receptors within the immune system. Among these receptors TLR4 is activated in response to bacteria and other non-bacterial ligands such as heat shock proteins, small fragments of hyaluronan, and even oxidised low density lipoproteins (oxLDL) in immunocompetent cells. TLR4 expression has been described in monocytes and microphages. TLR4 and different macrophage subsets have been shown to be implicated in inflammatory related diseases suggesting that understanding mechanisms of modulation of TLR4 signalling may be of great importance for pharmacological treatment of atherosclerosis.
Although existing TLR4 antagonists have been discontinued from clinical trials due to lack of efficacy, recently, a novel compound family designed as small molecule TLR4 antagonists have been developed to specifically modulate TLR4 signalling. We have recently shown that one of these molecules (AXO-102) negatively regulated in vivo and in vitro TLR4 signalling in vasculature and inhibited early rupture and incidence of aneurysms formation.
Main goal: This project will investigate the potential of IAXO-102 and other mimetic molecules to modulate the macrophage polarisation (formation of specific subsets) in response to sterile inflammation.
There are three main objectives:
Methodology: Cell culture and cell-based essays, western blotting, ELISA and antibody array approaches.
Collaborations: This project is based on academic and industrial collaborations with Reading University and Innaxon, UK respectively.
Outcomes: The results from this study will validate the potential of novel TLR4 antagonists as candidates for pre-clinical studies for pharmacological intervention of atherosclerosis.
This project is self-funded.
Details of studentships for which funding is available are selected by a competitive process and are advertised on our jobs website as they become available.
If you wish to be considered for this project, you will need to apply for our Biomedical Science PhD. In the section of the application form entitled 'Outline research proposal', please quote the above title and include a research proposal.
Cardiovascular, Translational Biomedicine
Various disease states damage the function of blood vessels, including diabetes, atherosclerosis and bacterial infections. The level of injury is dependent on the physiological insult and vascular bed. Maintenance of an intact endothelium is vital to prevent infiltration of immune cells or fluids. Platelets interact with the endothelium under conditions where the vessel wall is damaged, resulting in adhesion and aggregation of platelets to form a clot and arrest bleeding. The cell signalling mechanisms which regulate endothelial integrity and platelet aggregation are currently studied however the precise molecular mechanisms resulting in breakdown of barrier integrity and subsequent platelet interactions is not wholly understood.
The project will investigate novel mechanisms which regulate the cross-talk between the platelets and endothelium in settings of vascular disease. In particular, the research will focus on systemic factors associated with diet and the microenvironment at sites of vascular injury.
Research methods will include cell culture and platelet aggregation studies, as well as biochemical assays such as Western blotting and PCR analysis.
This project is self-funded.
Details of studentships for which funding is available are selected by a competitive process and are advertised on our jobs website as they become available.
If you wish to be considered for this project, you will need to apply for our Biomedical Science PhD. In the section of the application form entitled 'Outline research proposal', please quote the above title and include a research proposal.
CardiovascularCardiovascular
Atherosclerosis is a disease of the arteries which develops from localised inflammation in the artery wall. This occurs concomitant with a build-up of fatty deposits, dead cells and mineral deposits at these sites. Everyone develops some degree of atherosclerosis and overtime, depending on genetic and lifestyle factors such as a fatty diet and exercise, these lesions can become weak and rupture. A ruptured lesion will cause localised blood clotting. These clots can break away from the vessel wall and migrate with the blood flow to smaller arteries where blockage can occur, causing vascular diseases such as heart attacks, stroke and peripheral limb ischaemia. Currently, 420 people a day in the UK will die from cardiovascular diseases, with 7 million people living with the consequences of the disease.
Atherosclerotic inflammation and mineralisation are considered to be the end points of the development of atherosclerotic lesions. Thus, these two processes have the potential to be used as markers of atherosclerotic lesions likely to rupture, and may help in indicating patients at risk of developing the clinical consequences (heart attack and stroke). The mineral deposits in atherosclerotic lesions are formed from calcium hydroxyapatite deposition in a manner similar to bone formation. Bone material is produced by osteoblasts and osteoblast-like cells have been found in atherosclerotic lesions. These cells are thought to arise by the transformation of the resident vascular smooth muscle cells to an osteoblast-like phenotype. However, the biological processes regulating the cell transformation and subsequent mineralisation remain unclear.
This project will investigate novel mechanisms by which mineralisation occurs during the development of atherosclerosis and in particular, the role that localised inflammation plays in this process. The main objectives are to:
Research methods will include cell culture studies and biochemical assays including Western blotting, ELISA and qPCR analysis.
The expected outcome is an improved understanding of the processes by which vascular smooth muscle cells are induced to adopt an osteoblast-like phenotype and in particular, the signalling mechanisms involved.
This project is self-funded.
Details of studentships for which funding is available are selected by a competitive process and are advertised on our jobs website as they become available.
If you wish to be considered for this project, you will need to apply for our Biomedical Science PhD. In the section of the application form entitled 'Outline research proposal', please quote the above title and include a research proposal.
Cardiovascular, Connective tissue, Translational Biomedicine
Osteoarthritis (OA) is the most frequent of the arthritides with an incidence of 1 in 10 in those over 60 years of age. The disease is typified by the degradation and chronic loss of the cartilage that covers the ends of the bones. Currently, there is no cure for osteoarthritis beyond pain relief and joint replacement. Hyaline cartilage functions by providing both low friction surfaces in the joint and impact absorbance during locomotion. Chondrocytes are the principal cell type of hyaline cartilage and produce the extracellular matrix (ECM) which, provides the tissue with the capacity to resist mechanical load. The progression of the disease is characterised by an irreversible loss of the tissue and by chondrocyte cell death.
Osteoarthritis is linked most frequently to the “wear and tear” processes accompanying a lifetime of joint use and episodic joint inflammation. This project will investigate novel mechanisms involved in cartilage degradation and in particular, the intracellular signalling pathways, which regulate the degradative processes.
This project will investigate the mechanisms by which cartilage is induced to degrade, using cell culture models. The main objectives are to:
Research methods will include tissue and cell culture studies, and biochemical assays including Western blotting, ELISA, zymography and qPCR analysis.
The expected outcome is an improved understanding of the signalling mechanisms involved in cartilage degradation, which may identify future therapeutic targets for reducing the degradation of cartilage in the arthritides.
This project is self-funded.
Details of studentships for which funding is available are selected by a competitive process and are advertised on our jobs website as they become available.
If you wish to be considered for this project, you will need to apply for our Biomedical Science PhD. In the section of the application form entitled 'Outline research proposal', please quote the above title and include a research proposal.
Around 12 million people in the UK are diagnosed with respiratory diseases such as obstructive pulmonary disease, respiratory distress syndrome and pulmonary hypertension. Patients with respiratory disease suffer from a range of pathologies, such as hypoxia and pulmonary edema, associated with cardiovascular complications and increased mortality. One of the hallmarks of this group of diseases is disruption of the pulmonary microvasculature however despite significant efforts in the field, there is still no effective treatment to reduce this injury in patients with respiratory disease.
In respiratory diseases, there is an increase in oxidative stress and actin remodelling in the pulmonary endothelium, resulting in breakdown of the vasculature. We have identified a novel protein in the pulmonary endothelium, p18/LAMTOR1, which is downregulated in respiratory disease models. Proposed studies are needed to understand the mechanism through which this novel protein maintains a healthy endothelium. The research question for this PhD project is therefore: does p18/LAMTOR1 regulate oxidative stress and actin remodelling in the pulmonary endothelium? Proposed studies will address a new area of research which will develop our understanding of p18/LAMTOR1 in the endothelium and provide data to support a potential therapeutic target to improve microvascular function in patients with respiratory diseases.
Research will be performed using a range of in vitro techniques with healthy pulmonary arterial endothelial cells (HPAEC) to measure the role of p18/LAMTOR1 in regulating oxidative stress, actin remodeling and barrier function in the pulmonary endothelium.
Findings are anticipated to establish p18/LAMTOR1 as a key protein which regulates the pulmonary endothelium. The PhD will give insight into the mechanism through which p18/LAMTOR1 maintains the endothelium and expand our understanding of the novel role of the protein in the lung. Studies are anticipated to implicate p18/LAMTOR1 as a therapeutic target in maintaining a healthy endothelium.
This project is self-funded.
Details of studentships for which funding is available are selected by a competitive process and are advertised on our jobs website as they become available.
If you wish to be considered for this project, you will need to apply for our Biomedical Science PhD. In the section of the application form entitled 'Outline research proposal', please quote the above title and include a research proposal.
Increased gastric permeability is associated with metabolic diseases such as diabetes and obesity. Maintenance of a healthy, intact intestinal epithelial barrier is vital to prevent inflammation and septicemia seen in these diseases. The intact barrier is preserved through the formation of junctional complexes between intestinal epithelial cells. We have recently shown that the activation of sweet taste receptors, by sweeteners, increases leak across the intestinal epithelium by breakdown of these junctional complexes. We have further demonstrated that sweeteners increase the ability of model bacteria, in the gut microbiota, to damage intestinal epithelial cells. In contrast, far less is understood about bitter taste sensing in the intestinal epithelium, despite the high number of bitter taste receptors in the G-protein coupled receptor family. Interestingly, increased expression of bitter taste receptor T2R38 observed in the specialized gastrointestinal tract cells of obese patients. Preliminary studies from the laboratory, using intestinal epithelial cells, show that stimulation of T2R38, by phenylthiourea, increases breakdown of tight junctions maintaining the epithelial barrier and increased leak. The research project will therefore address the hypothesis that bitter taste sensing regulates the intestinal epithelium through acting on microbiota and intestinal epithelial cells. By understanding the mechanisms regulating these processes, we aim to develop novel therapeutic targets to improve intestinal epithelial barrier function and therefore reduce inflammation and septicaemia in patients with metabolic disease.
To test this hypothesis, studies will be performed using a combination of microbiology and cell culture studies using two model gut bacteria (E.coli NCT, E. faecalis) and a transformed cell model of the intestinal epithelium (Caco-2 cells). These two models, currently used in the laboratory, will be studied as a co-culture using bitter taste agonists to study the functional response. Key outcomes are changes in metabolism or pathogenic effect of bacteria on the epithelium and breakdown of the intestinal epithelial barrier.
Findings from the project will demonstrate the molecular mechanisms through which activation of bitter taste receptors can regulate function of the intestinal epithelium. This investigation is anticipated to demonstrate that taste receptors represent novel therapeutic targets in the treatment of inflammation and septicaemia in patients with metabolic diseases.
This project is self-funded.
Details of studentships for which funding is available are selected by a competitive process and are advertised on our jobs website as they become available.
If you wish to be considered for this project, you will need to apply for our Biomedical Science PhD. In the section of the application form entitled 'Outline research proposal', please quote the above title and include a research proposal.
The 'One Health' concept recognises that human and animal health are interconnected and that bacteria can be transmitted from humans to animals and vice versa. The impact of this initiative is now even more apparent with the global burden of antimicrobial resistance (AMR). 'One Health' also recognises that the environment is a key component of the link between humans, animals and the spread of new resistant microorganisms. Microbial source tracking has demonstrated how critical the environment is with regards to the persistence and re-infection potential of pathogens in animal reservoirs, such as bird faeces. Furthermore, research has shown that birds facilitate the spread of AMR through faeces.
The United Nations General Assembly underlined the threat of AMR and committed to join forces and prevent its spread. AMR is predicted to cause 10 million deaths and have a serious economic impact by 2050 if no action is taken. Fluoroquinolone-resistant Salmonella spp. are on the 2017 WHO list of pathogens in need of urgent research to develop new antibiotics. In order for such research efforts to take place, it is imperative that the mechanisms underlying fluoroquinolone-resistance in Salmonella spp. are elucidated. Thus, it is important to analyse field isolates which potentiate infection and resistance spread.
This PhD project will use whole-genome sequencing to determine fluoroquinolone-resistance profiles of field isolates collected from bird faeces in recreational areas around the UK. This monitoring is essential to evaluate how phylogenetically-related the isolates are and understand potential evolutionary patterns of the development of AMR in fluoroquinolone-resistant Salmonella spp. Preliminary work in our laboratory has identified ~50 isolates of Salmonella spp. collected from bird faeces in recreational areas. The project will use these samples but also perform further fieldwork therefore, some travelling around the UK will be necessary. The isolates have been phenotypically tested for resistance to fluoroquinolones using EUCAST standard procedures. A substantial part of the project will be analysing genome data, annotating and identifying resistance genes. Once the mechanisms of resistance have been identified allele-replacement mutagenesis will be used to knock out these mechanism(s) and the resistance phenotype will be re-tested to prove the involvement of specific genes.
This project is self-funded.
Details of studentships for which funding is available are selected by a competitive process and are advertised on our jobs website as they become available.
If you wish to be considered for this project, you will need to apply for our Biomedical Science PhD. In the section of the application form entitled 'Outline research proposal', please quote the above title and include a research proposal.