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Biomedical Sciences Masters by Research

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Biomedical Sciences Masters by Research

Projects and Supervisors

Choose from the projects listed below.

Applicants will be expected to have experience and evident knowledge of molecular cell biology, biochemistry.

Dr Hrvoje Augustin
Biology of ageing: investigating the effect of novel compounds on longevity and functionality

One of the goals of ageing research is to identify compounds that can extend lifespan and/or improve physical and cognitive performance in old age. The research of the last 20 years revealed a high level of conservation of genetic pathways and biochemical processes that regulate lifespan in organisms as diverse as yeast, worms, flies and humans. The fruit fly Drosophila, in particular, emerged as a pre-eminent model system for studying changes that occur during both normal and pathological ageing (~75 per cent of the genes that cause disease in humans are also found in the fruit fly!). The advantages of Drosophila include their relatively low cost, ease of use and a range of powerful tools available for their genetic manipulation.

Our Department recently identified several compounds with possible pro-longevity effects. The aim of this project is to assess the effect of these compounds during healthy ageing and in various Drosophila models of human diseases. The initial lifespan studies will be followed by an array of molecular, biochemical, imaging and functional analyses.

Modelling dementia-related synaptic dysfunction in Drosophila

Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD) are the most common causes of neurodegenerative dementias. These diseases are characterised by presence of various types of aggregates of misfolded proteins in the neuronal tissue; however, evidence suggests that dysfunction and loss of the synapse might be a common pathological feature underlying the cognitive decline and memory loss in these neurodegenerative disorders.

An intronic GGGGCC hexanucleotide repeat expansion in the C9orf72 gene is the most common genetic cause of both FTD and Amyotrophic Lateral Sclerosis (ALS). We will first overexpress the mutated form of C9orf72 in Drosophila larval motor neurons innervating the neuromuscular junction, causing a drastically reduced transmission across the synapse. We will then screen the fruit-fly genome searching for the genes that can correct (‘cure’) this synaptic phenotype. The genes identify in the screen can be potential targets for therapeutic interventions in humans. Electrophysiology will be used as the primary screening tool. Other techniques: confocal microscopy, genetics and biochemistry/molecular biology.

Dr Philip Chen
Pharmacology of glycine-site agonists at NMDA receptors

This project will characterise a number of novel agonists at NMDA receptors using molecular biology and recording glutamate evoked inward currents from oocytes injected with mutant NMDARs under two-electrode voltage clamp configuration. The project will involve molecular techniques such as subcloning, site-directed mutagenesis, PCR and in vitro cRNA synthesis, injection of cRNA into Xenopus oocytes and two-electrode voltage clamp electrophysiology.

Examining the consequences of altered RNA editing on neuronal function

RNA editing is a process by which specific nucleotides are modified following gene transcription and disruptions in these processes have been linked to certain neurodegenerative conditions. We have developed a number of genetic tools to manipulate RNA editing and would like to explore their consequences on cell function. This project would involve mammalian tissue culture, RNA extraction, cell transfection and RT-PCR.

Research page - Dr Chen

Professor Simon Cutting
Mucosal vaccines

Work consists of innovative bacterial delivery systems for mucosal vaccination (i.e. against malaria or TB). Due to the dynamics of our projects, they are ongoing and subject to change on a regular basis and cannot be specified in advance.

Research pages - Professor Cutting

Dr James McEvoy
Antibiotic resistance in bacterial biofilms on orthopaedic pins

Bacterial biofilms are a common cause of infection in surgical implants, and pin tract infection is the major complication of external fixation of fractures. Furthermore, biofilm-focused infections are phenotypically resistant to antibiotic therapy. In this microbiological project, run in collaboration with Dr Shobana Dissanayeke (Royal Holloway) and Mr Arshad Khaleel (St Peter’s Hospital, Chertsey), you will use a bioreactor to grow bacterial biofilms on orthopaedic pins and study their response to antibiotic treatments. Guided by recent results from our laboratory1 you will investigate the social aspects of genotypic antibiotic resistance in multi-strain biofilms, extending this work by the addition of clinically relevant b-lactamase inhibitors. Our long-term objective is to inform surgical practice and reduce pin tract infection rates.

1. Amanatidou, E.; Raymond, B., Biofilms facilitate cheating and social exploitation of β-lactam resistance in Escherichia coli. npj Biofilms and Microbiomes 2019, 5, 36-36.

Research pages - Dr James McEvoy

Dr Linda Popplewell
Optimisation of antisense oligonucleotide-induced exon skipping as a therapy for Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD), a severe muscle-wasting disease due to a lack of dystrophin protein, is caused by mutations in the DMD gene. Antisense oligonucleotides (AOs) can be used to restore the transcript reading frame so that truncated but functional dystrophin protein is expressed. Clinical trials show that such a therapy appears to halt the progression of the disease. The aim of this project would be to enhance the levels of exon skipping seen using alternative AO delivery methods, and modulators of gene expression so that therapeutic benefit is enhanced.

Upregulation of utrophin expression as a therapy for Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD), a severe muscle-wasting disease due to a lack of dystrophin protein, is caused by mutations in the DMD gene. Utrophin is a structural homolog of dystrophin protein and can act as its substitute at the sarcolemma. Upregulation of utrophin expression has been achieved using small molecule interaction with its promoter. While good results are evident in animal models, effects appear to be limited in clinical trial. The aim of this project would be to examine alternative strategies to upregulate utrophin expression using the CRISPR system together with transcriptional activators.

Research pages - Dr Popplewell

Professor Pankaj Sharma
Epidemiology of global stroke in South Asians

You will be based in a group headed by a clinical academic.

Stroke is the third commonest cause of death in the UK. WHO estimates that by 2050 around 80% of all stroke will be in India and China. Our group has amassed the largest database of South Asian stroke in the world. We have data from UK, India and the Middle East.

It is expected that these projects will lead to publications in major international peer review journals.

This project will allow students to analyse this extensive database to search for interactions between stroke and established risk factors

Risk factors in South Asian stroke

You will be based in a group headed by a clinical academic.

Stroke is the third commonest cause of death in the UK. WHO estimates that by 2050 around 80% of all stroke will be in India and China. Our group has amassed the largest database of South Asian stroke in the world. We have data from UK, India and the Middle East.

It is expected that these projects will lead to publications in major international peer review journals.

This project will allow students to analyse this extensive database to search for novel risk factors in South Asians and compare and contrast such factors with stroke in Caucasians.

Designing a new strategy for ‘five-a-day’ intake

You will be based in a group headed by a clinical academic and be supervised by two clinicians.

The 5-a-day campaign was launched by the UK Government to ensure that the population eats at least five fruit and vegetables per day. Research suggests that those that do this have a lower risk of cardiovascular disease.

However, the evidence is that most people do not remember how many of their 5-a-day they have eaten. We propose to develop a new colour based flag strategy for each meal to replace the 5-a-day slogan.

This work potentially has large and important clinical and public health implications.

Research pages - Professor Sharma

Dr Mikhail Soloviev
Cryptanalysis of recombinant DNAs

Naturally occurring DNA typically has coding and non-coding regions (genes and various regulatory sequences respectively), there is also mitochondrial DNA and chloroplast DNA in plants. The genome complexity and chemical nature varies considerably between Viral, Prokaryotic and Eukaryotic genomes. A large number of recombinant (artificially created) DNA and RNA sequences have been deposited into sequence databases in the last few decades. Most of these sequences encode expression vectors, native or modified recombinant proteins, and a number of structural nucleic acids. But Nucleic acid sequences contain much more information than just the encoded coding and non-coding regulatory sequences. This project aims to decipher the hidden complexity of recombinant nucleic acid sequences with the view to develop algorithms to assist identifying artificially created sequences form naturally occurring ones. The algorithms will be applied to analyse viral DNA or RNA genomes in sequence databases which became available recently.

Antigenic epitopes: prediction and validation. Antigenic epitopes of COVID protein antigens.

Generation of high affinity antibodies against given antigens for therapeutic or biotechnology applications is among the major challenges for the biopharmaceutical industry. Recombinant therapeutic proteins and antibodies occupy almost all of the top 20 places in the list of best-selling medicines over the last decade. One of the challenges in generating useful antibodies relates to the selection of antigenic epitopes. This project will build upon the previous of our recent research and will also include analysis of the Immune Epitope Database (IEDB) and Virus Pathogen Resource (ViPR) with the overall aim to develop algorithms for selecting antigenic epitopes for generation of high affinity antibodies. These will be tested and validated experimentally using polyclonal antipeptide antibodies developed against the receptor binding domain of the Spike protein (S) exposed on the SARS-CoV-2 viral envelope. Such antibodies will be used for the development of a point of care (POC) antibody based test for detecting COVID-19. The methods can be adapted to target other common viruses.

DNA based multiplex detection of viral infections

Clinical diagnosis of Coronavirus is often achieved using real time PCR (RT-qPCR) to detect minute quantities of viral RNA fragments in the samples tested. The use of suck kits has increased substantially during the 2020 COVID-19 pandemic.  Many different coronaviruses exist in the family of Coronaviridae. Some of these infect humans, causing mild (common cold) or severe acute respiratory syndrome (SARS viruses). Coronaviruses may infect a range of farm animals causing serious problems to the farming industry. A qPCR based test is relatively simple and is very sensitive. Ultimate sensitivity for the detection of a single RNA deletion is achievable in principle. But PCR/RT-PCR tests are often limited to the analysis of a single RNA or DNA target. PCR reaction may be multiplexed but only to a limited degree. This project aims to devise a simple single PCR reaction based test capable of detecting many common strains of the coronavirus in a single test reaction. This technology may be applied to human rhinoviruses (common cold) of which about 160 recognized types are known.

Engineering of Protein-A derivatives for biotechnology applications

Staphylococcal Protein A (Protein A or "SPA") is a 42 kDa virulence factor produced by Staphylococcus aureus (S. aureus) in its cell wall. SPA is well known for its ability to bind IgG molecules with very high affinity. It is widely used in biotechnology applications, such as antibody capture, immobilisation or purification to name just a few. SPA has been used widely in Life Sciences, but it has a few serious limitations. SPA recognises and binds IgGs of many different isotopes, but not all. For example native SPA does not recognise or binds human IgG3 and a few other IgGs. This severely limits its application range. This project aims to engineer SPA analogues capable of binding human IgG3. This research has huge commercial implications.

Protein based assays for POC molecular diagnostics

In the course of our current research we developed antibodies against a range of known and putative cancer markers and also against known acute-phase proteins. This project will explore multiplexing options for use with the available antibodies in order to create a point of care (POC) diagnostic assay for health monitoring and early cancer detection. A large selection of antibodies is available for the student to choose the preferred research focus (cancer, inflammation, health monitoring and forensic applications).

Serum Albumin as a drug-carrier protein for therapeutic applications

The efficacy of a therapeutic drug is affected by many factors, among which bioavailability, serum half-life, organ targeting, dosage and side effects play major roles. Serum albumin is the most abundant protein in blood serum in humans. One of the major roles of Albumin is to serve as a carrier protein for low molecular weight (LMW) molecules such as fatty acids, hormones, peptides and small serum proteins. Albumin binds many LMW therapeutic molecules, which affects their free and total serum concentrations, hepatic and renal clearance and therefore serum half-life, which will strongly influence the drug pharmacokinetics and the drug-dosing regimen (for a brief review see Merlot et al 2014). Albumin has multiple LMW binding sites and has been shown to interact with a multitude of LMW molecules and drugs (for a summary of drugs and methods used see Shahani 2014). Another widely investigated approach to utilize albumin for drug delivery requires generating albumin based nanoparticle-drug conjugates (for a recent review see Lamichhane and Lee 2020). This project aims to use a combination of chromatography, mass spectrometry, fluorescence analyses and other analytical tools and methods to study drug-albumin interactions. One other research option will focus on exploring stimuli-sensitivity of Albumin for remotely controlled drug delivery and release.

Stimuli-responsive biopolymers for life science, materials and therapeutic applications

The scientific motivation behind this project is to generate remotely controlled molecular systems capable of changing their physical or molecular properties in response to external stimuli. Such stimuli include but are not limited to ultrasound, electromagnetic radiation, exposure to infrared light, thermal, mechanical or chemical stimulation. We have developed a number of thermally activated protein-based systems. One such system comprises a range of sequence specific self-assembling polypeptides developed in collaboration with the University of Lincoln and the UK’s national synchrotron science facility Diamond Light Source Ltd. A common feature of these molecular systems is the ability to self-assemble and then disassemble in response to thermal stimuli. Another important feature is the ability to carry and release therapeutic load. Combining such systems with stimuli-specific sensitive elements such as light excitable groups, magnetic nanoparticles, elastic nanoparticles, chemically modifiable groups and their combinations yields highly tuneable stimuli-responsive biomaterials suitable for a variety of life science and therapeutic applications.

The key aim of this project is to engineer new biomaterials by combining multiple stimuli-specific sensors with functional biological molecules and to test physical, chemical and biological properties of the newly generated smart composite biomaterials. Due to the multidisciplinary nature of this research project, applications from students with the background in physics, chemistry, biophysics, biochemistry, nanomaterial and protein based therapeutics are especially welcome. 

Recent publications by the group MSc students:

Research pages - Dr Soloviev

Dr Jorge Tovar
In vitro study of the cell-cell interactions between Aspergillus fumigatus and Bdellovibrio relevant to cystic fibrosis patients.

Cystic fibrosis (CF) is a genetic disorder caused due to mutations in CFTR gene. The gene is important for the regulation of epithelial fluid transport in the exocrine glands, situated largely in respiratory and alimentary systems. The lung of CF patients is increasingly found co-infected with fungal and bacterial pathogens (deDios et al, 2017; Middleton et al, 2013). Staphylococcus aureus, Haemophilus influenzae, and Pseudomonas aeruginosa are the most common bacteria found in the CF lung. Aspergillus spp., Candida spp., Scedosporium spp., and Exophiala spp. are the most frequently detected fungi (Williams et al, 2016), with a reported 10-57% prevalence for A. fumigatus (deVvrankijker et al, 2017).

Recently published research identified the presence of two predatory bacteria in CF lung microbiota, Bdellovibrio and Vampirovibrio. They limit CF pathogens by feeding on them (deDios et al, 2017). Interestingly, their predatory effect on fungi has not been investigated. This project will aim to understand the interaction between A. fumigatus and Bdellovibrio at the cellular level and will provide training in microbiology and advanced microscopy skills (brightfield and confocal). If Bdellovibrio can exert fungicidal or static effects it could potentially be used to treat CF patients and other manifestations of aspergillosis

Developing novel platforms for the molecular diagnosis of fungal infections

Human fungal infections represent one of the most pressing health problems in recent years. Endemic infections affect healthy immunocompetent individuals causing a range of diseases which generally resolve with chemotherapy but hospital-acquired nosocomial infections pose a serious threat to immunocompromised patients in hospital wards and intensive care units worldwide. Despite the availability of chemotherapy nosocomial infections frequently result in high mortality rates, often exceeding 50%. The development of timely and more efficient molecular diagnostic methods, along with the development of new drugs and anti-fungal vaccines, was recently identified as one of the most pressing needs in medical mycology research.

We are interested in developing and implementing simple nucleic acids diagnostic tests for a range of fungal infections, including both endemic and opportunistic. Using fungal genome data mining and isothermal DNA amplification this project will use Candida – the causative agent of endemic and nosocomial candidosis – to develop simple diagnostic tools that are both amenable to automation and applicable at the point of care.

Research pages: Dr Tovar

Dr Chris Wilkinson
Centrosomes and melanoma

Centrosome aberrations are a hallmark of cancer. Excessive centrosome numbers are thought to drive carcinogenesis by contributing to aneuploidy and chromosomal instability. However, much remains to be understood about the origin and the contribution of excessive centrosomes in tumorigenesis. This Masters project will test if centrosomal abnormalities correlate with progression of melanoma and investigate if this is driven by loss of INK4 proteins p15 and p16. A combination of cell biology, immunocytochemistry, epifluorescence microscopy and protein analysis such as Western blotting will be used in this project.

Role of the centrosomin family of proteins in microcephaly and early neurogenesis

Primary microcephaly is a disease in which the size of the brain is much reduced but normal tissue architecture retained. Last year we showed that loss of many of the genes mutated in microcephaly results in a slow cell cycle, in a zebrafish model of the disease. We’d like to extend this study by looking at embryonic zebrafish brains. It is also a mystery why the brain alone is affected. In the case of one of the genes mutated, there is a sister protein with which it might be partially redundant. In this project, we will deplete this protein from zebrafish embryos and investigate the effect using a combination of zebrafish cell culture, embryology and confocal fluorescence microscopy.

Role of a polycystin-interacting protein in ciliogenesis

Cilia are hair-like structures on the surface of many animal cells. They have important roles in cell signalling and tissue development and homeostasis. Cilium malfunction is linked to autosomal dominant polycystic kidney disease (ADPKD), which affects 1 in 1,000 of the population, as the cilium houses polycystin-1 whose gene is frequently mutated in ADPKD. This project will investigate the role of a protein that interacts with polycystin-1, discovered by our collaborator, Richard Sandford at Cambridge. A variety of cell biology and embryological techniques will be used to investigate its function using tissue culture cells and zebrafish embryos.

Research pages - Dr Wilkinson

Professor Robin Williams
Bipolar disorder, inositol depletion and the model system Dictyostelium

Bipolar disorder is a common neuropsychiatric disorder that is associated with an increased likelihood of suicide. Research in this field is difficult, since few molecular targets are known, and experimental approaches are almost entirely based upon animal models. One strongly supported mechanism of how bipolar disorder drugs work is the ‘inositol depletion’ hypothesis, which states that treatments such as valproic acid function to deplete inositol within neurons to control an individual’s emotional state. This effect may involve the regulation of the biosynthetic enzyme, inositol synthase. Using Dictyostelium as an animal replacement model, our recent data has identified several mechanisms by which inositol synthase acts. This project will employ Dictyostelium to identify how these mechanisms occur, without the use of animal models. Skills developed in the project will include a range of key molecular cell biology, microbiology and microscopy techniques.

Related research

Defining the primordial target for gamma-secretase in the social amoeba, Dictyostelium

Alzheimer’s disease is a devastating neurological disorder that is associated with changes in the activity of a highly conserved protein complex called gamma-secretase. Research in this field is increasingly breeding genetically modified animals as a model for study, and thus alternate non-animal models are needed to reduce animal experimentation. We have recently shown that the key human protein within this complex, presenilin 1, is active in the social amoeba, Dictyostelium. The substrates for the complex are well characterised in humans, however, no substrate has been identified in Dictyostelium. This project will involve the identification and characterisation of a potential Dictyostelium gamma-secretase substrate that will help to unravel the primordial role of this important complex, without the use of animal models. The project will involve the genetic ablation and over-expression of a fluorescently tagged gene in Dictyostelium. Skills developed in the project will include a range of key molecular cell biology, microbiology and microscopy techniques.

Related research

Research Pages - Professor Williams

Professor Rafael Yanez
Gene therapy, viral vector, Spinal muscular atrophy

Spinal muscular atrophy is an autosomal recessive disease and one of the most common and severe inherited disorders. Lack or inactivation of SMN1 leads to progressive degeneration of motor neurons in the spinal cord, causing bilateral muscular atrophy and death in the worst affected cases. We are aiming to develop genetic therapies for this disease with the goal of preventing or slowing down motor neuron degeneration. The project will involve molecular cloning, production of viral vectors and initial testing in cell culture. The expected outcome is lentiviral vectors with the capacity to improve survival of motor neurons.

Research pages - Professor Yanez

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