Master’s by Research opportunities

Biosciences at Kent offers five Master’s by Research courses in Biochemistry, Cell Biology, Computational Biology, Genetics, and Microbiology. Each offers a range of projects – scroll down to discover more.

How to apply

Once you have identified a project you are interested in, contact the named supervisor by email to discuss the possibility of undertaking an MSc under their supervision. Please outline your interest in the research project and supply a CV, including all relevant experience and details of how you will fund your study. After securing a project and a supervisor, you can proceed to make an online application.

For further information on how to apply online for Postgraduate research degrees, see our website. Alternatively, please contact information@kent.ac.uk with any questions on how to proceed.

Please note that additional research fees of £1,500 apply to each of the listed projects.

Our projects

Click on the headings for details of the projects offered:

AI and Data-Driven Biosciences

Antimicrobial Resistance, Infection and Immunity

Cancer Biology and Ageing

Disease, Diagnostics and Therapeutics

Engineering Biology

Genomics, Evolution and Reproductive Biology

Integrated understanding of health

Sustainable agriculture and food

Understanding the rules of life

AI and Data-Driven Biosciences


Using a novel pressure perturbation imaging system to understand cell growth and disease
Supervisor: Professor Daniel Mulvihill
Course: Biochemistry, Cell Biology, Microbiology

Novel technologies have driven many periods of rapid progress in science. This is exemplified in the novel imaging technologies that allow molecular dynamics to be followed within living cells with exquisite detail. Hydrostatic pressure has long been used to modulate protein and membrane structures and alter cytoskeleton dynamics and stall cell division in a fully reversible manner. However hydrostatic pressure has not been applied to fluorescence live cell imaging due to challenges in light path design. We have developed a novel live cell imaging system that allows visualisation of protein organisation and dynamics within live cells at 100 atmospheres pressure (J. Cell. Sci. 131, jcs212167–8). Here we will use this system to examine the impact pressure has upon cytoskeletal dynamics, growth and morphology of a range of cells, including bacteria and cultured human cells. to provide insights into the mechanisms that allow a cell to respond to their environment.

Bioinformatics Analysis of RUTF Impact on Microbiome, Metabolome, and Transcriptome Dynamics
Supervisor: Dr Anastasios Tsaousis
Course: Computational Biology

This project will leverage advanced bioinformatics techniques to analyse the complex interactions between Ready-to-Use Therapeutic Foods (RUTF) and the microbiome, metabolome, and transcriptome in a preclinical model. Using data from an established juvenile rat model, the student will assess the effects of RUTF on gut health, nutrient absorption, and systemic recovery, employing tools for next-generation sequencing data analysis, metabolomic profiling, and transcriptomic interpretation. The goal is to provide a comprehensive understanding of how RUTF interventions influence biological processes at the molecular level, which could lead to optimised formulations for treating malnutrition more effectively.

Exploring the influence of 3D DNA architecture and satellite DNA on Robertsonian Translocations in Bovids
Supervisor: Dr Marta Farre Belmonte
Course: Computational Biology, Genetics

Robertsonian translocations (Rbs) are a form of chromosomal rearrangement resulting from fusion of two acrocentric chromosomes and forming a metacentric chromosome. While Rbs have been observed in a wide range of taxa, including humans, their role in speciation and genetic diversity remains an active area of research. Rbs in bovids, a family that includes species such as cattle, sheep, and antelopes, are of significant interest due to their potential impact on reproductive isolation and speciation. The mechanism by which Rbs occur in the first place, and how the three-dimensional (3D) organization of DNA within the nucleus might influence this process is still unknown. The role of centromeric satellite DNA and the 3D spatial arrangement of chromosomes in the nucleus could be crucial to understanding why certain chromosomes are more predisposed to undergo Rbs than others. This project combines wet-lab work with bioinformatics, and it’s suitable for a student interested in both aspects.

Predicting protein function
Supervisor: Professor Mark Wass
Course: Computational Biology

Advances in sequencing technologies have identified millions of protein sequences but the function of many of these proteins remains unknown. This project will focus on developing a computational method to predict protein function.

Further reading:
Cell-Free Synthetic Biology: https://www.frontiersin.org/research-topics/12103/cell-free-synthetic-biology
Streptomyces CFPS: https://www.biorxiv.org/content/10.1101/2020.11.16.384693v2.full
An automated platform for ESKAPE pathogen antimicrobial discovery
The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp) are multidrug-resistant bacteria found in nosocomial clinical infections and a growing concern for hospitals; novel antibiotics with distinct modes of action are required. We are interested in the development of an automated workflow for novel antimicrobial discovery. We will specifically study methicillin-resistant Staphylococcus aureus (MRSA) for drug screening using a unique approach to detect bioactivity, potentially at a high-throughput scale.

Computational and integrative structural biology of amyloid assemblies
Supervisor: Dr Wei-Feng Xue
Course: Computational Biology, Biochemistry

The aim of this project is to identify and understand the structural organisation of amyloid aggregates using nano-scale imaging and integrative structural biology methods. In this computational project, training in image data analysis will be offered, and AFM image data in integration with cryo-electron microscopy data will be analysed using state of the art individual particle 3D reconstruction methods developed in the Xue lab to characterise and compare the molecular structures involved in the formation, growth and the division of amyloid aggregates grown from disease associated and functional amyloidogenic proteins. There will also be opportunities to learn computer coding and data analysis software algorithm development. This computational project can be carried out through remote working/hybrid arrangements.

Investigating determinants of virus pathogenicity
Supervisor: Professor Mark Wass and Professor Martin Michaelis
Course: Computational Biology

Our research has recently compared different species of Ebolaviruses to identify parts of their proteins that determine if they are pathogenic. This project will apply these computational approaches to different types of viruses (e.g. Zika virus, west Nile, human papillomavirus) to identify determinants of virus pathogenicity and gain insight into what make some viruses highly virulent while others are harmless.

Investigating the determinants of SARS Coronavirus-2 pathogenicity
Supervisor: Professor Mark Wass and Professor Martin Michaelis
Course: Computational Biology

Severe Acute Respiratory Coronavirus-2 (SARS-CoV-2) is currently causing a pandemic with much of the world in a lockdown state to limit the spread of the virus and number of cases and deaths that it causes. Due to the latest genome sequencing technologies there are now many thousands of SARS-CoV-2 genome sequences obtained from those infected. These can be analysed to advance our understanding of the genetic and molecular features that determine the properties of the virus. This project will focus on using computational approaches to compare the thousands of SARS-CoV-2 genome sequences with those of SARS-CoV, the related virus that caused the 2002-2003 SARS Coronavirus outbreak. While these two viruses are closely related there are important differences in the disease that they cause. For example, SARS-CoV-2 has a much lower death rate and appears to be more easily transmitted. We have already begun research in this area (see our preprint here: https://www.biorxiv.org/content/10.1101/2020.04.03.024257v1) and this project will expand on this work.

Antimicrobial Resistance, Infection and Immunity


Interplay between antimicrobials and nitric oxide: new strategies to combat drug-resistant bacterial infections (MSc or PhD)
Supervisor: Dr Mark Shepherd
Course: Microbiology

Recent work has revealed that nitric oxide (NO), a toxic free radical produced by the innate immune system in response to infection, has a dramatic impact upon the efficacy of selected antibiotics. However, very little is known about the impact of NO upon certain antibiotic classes, including nitrofurans that are used to treat urinary tract infections. This project seeks to characterise the effects of NO upon key antibiotic classes using a range of bacterial pathogens, including multidrug-resistant E. coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii. This work has the potential to pave the way for new strategies to combat drug-resistant bacterial infections.
Tag: Antimicrobial Resistance

Drug repurposing to target respiratory complexes of antibiotic-resistant bacterial pathogens
Supervisor: Dr Mark Shepherd
Course: Microbiology

Inhibition of the respiratory complex cytochrome bd is well-known to diminish survival of a variety of bacterial pathogens during infection. Recent work in the host lab has identified steroid drugs as excellent candidates to target cytochrome bd complexes in bacterial pathogens. The current project will involve screening steroid derivatives and related compounds to design new strategies to inhibit bd-type respiratory complexes, with a particular focus on Gram-positive species of Staphylococcus, Enterococcus, and Streptococcus.

Development of Novel Mitochondrial Targeted Antifungal Agents
Supervisor: Dr Dave Beal and Professor Campbell Gourlay
Course: Microbiology, Biochemistry, Chemistry

Acquired drug resistance is a major concern for the future treatment of fungal pathogens like Candida albicans etc. A lack of new drug molecules with novel mechanisms of action is a major cause of this problem. In this project an exciting lead compound which targets the electron transport chain, developed between the Beal and Gourlay labs, will be modified to allow for targeting to the mitochondria. This is an exciting project focused on an important area of research. Skills developed: Synthetic organic chemistry, biochemistry, molecular biology, analytical chemistry.

Development of a Commercial High-Throughput Solution for Antibiotic Uptake and Permeation
Supervisor: Dr Jose Ortega Roldan
Course: Biochemistry

Drug development often focuses on targeting specific sites without ensuring the drug can effectively enter cells, a critical factor for efficacy. Cellular membranes vary across species, strains, and disease states, yet no high-throughput methods currently exist to assess drug uptake efficiency. This limitation significantly impacts drug development, with 90% of candidates failing due to poor cellular entry, costing $100 million per failure. Existing models for permeability testing, such as intestinal or blood-brain barrier assays, are costly and not always suitable for antibiotic development. This research aims to validate and commercialize a novel high-throughput drug uptake assay using a plate-based flow system and fluorescence reporter technology. Key objectives include expanding drug compatibility, validating the system for antimicrobials, and developing a commercialization strategy. By creating a cost-effective, scalable solution, this project will enhance drug development efficiency, improving the success rate of new treatments for infections and diseases.

Elucidating fungal immune evasion strategies
Supervisor: Dr Rebecca Hall
Course: Microbiology

Innate immunity is key for protection against fungal pathogens, providing selective pressure on fungi to evolve immune evasion strategies. Candida albicans is a commensal and opportunistic fungal pathogen, that can evade the immune system by remodelling its cell wall to prevent recognition of glucan, or by inactivation of the alternative complement system. However, C. albicans has other, yet to be discovered, mechanisms to avoid detection from our immune system. In this project you will combine host-pathogen interaction screens and fungal molecular biology (i.e. CRISPR) to determine how C. albicans evades the immune system. This all-encompassing project will provide a step-change in our understanding of fungal pathogenicity and will lead to the identification of new therapeutic targets which can be exploited to restore immune recognition and prevent infection.

Investigating the Mucorales host-pathogen interaction
Supervisor: Dr Rebecca Hall
Course: Microbiology

Mucormycosis is a deadly infection caused by fungi belonging to the Mucorales order. Although once a rare infection, the SARS COVID-19 pandemic resulted in a surge of mucormycosis infections, especially in India. Despite the severity of this infection, we still have a limited understanding of the pathobiology of these fungi. In this project you will combine host-pathogen interaction assays, cell biology, microbiology and microscopy techniques to further our understanding of the interaction of this order of fungi with the innate immune system.

The role of circadian rhythms in microbial infection
Supervisor: Dr Rebecca Hall and Professor Gurprit Lall
Course: Microbiology, Cell Biology

The circadian rhythm is a natural internal body clock that regulates biological and behavioural activities on a 24-hour cycle. Various aspects of the innate immune system are regulated by the circadian rhythm including the activity and number on innate immune cells such as macrophages and neutrophils. These innate immune cells are essential for combatting fungal infections. Therefore, understanding the link between the circadian rhythm and fungal innate immune responses is vital for combating fungal infections. In this project you will develop circadian reporter systems and combine host-pathogen interaction assays with fungal molecular biology to understand the role of the circadian rhythm in anti-fungal immune responses, and how disruption of this clock can affect our risk of developing infections.

Examining the drug resistance properties of clinically relevant biofilms
Supervisor: Professor Gurprit Lall
Course: Microbiology

Biofilms, complex communities of microorganisms encased in a self-produced extracellular matrix, play a critical role in persistent infections. In clinical settings, biofilm-associated infections are particularly challenging to treat due to their heightened resistance to antimicrobial agents. This resistance arises from multiple factors, including limited drug penetration, altered metabolic activity, and the presence of persister cells. Understanding the mechanisms that drive drug resistance in biofilms is essential for developing more effective therapeutic strategies. In this project we will explore how host proteins, such as amylase and haemoglobin are assimilated into polymicrobial biofilms and explore novel approaches to their prevention.

Employing probiotic lipids to prevent biofilm formation on medical devices
Supervisor: Professor Gurprit Lall
Course: Microbiology

Biofilm formation on medical devices, such as catheters, prosthetic joints, and implants, presents a significant challenge in clinical settings due to its strong resistance to antimicrobial treatments. These biofilms, composed of microorganisms embedded in a protective extracellular matrix, limit drug penetration, alter microbial metabolism, and harbor persister cells, making infections difficult to eradicate. As a result, biofilm-associated infections can lead to prolonged treatments, device failure, and increased patient risk. In this project we will follow a promising new approach that employs pro-biotic lipid formulations to coat medical devices to prevent biofilm formation.

Caught in a TRAP: probing the mechanism of tripartite ATP-independent periplasmic (TRAP) transporters as new antimicrobial targets
Supervisor: Dr Chris Mulligan
Course: Microbiology, Biochemistry

The uptake of nutrients from the environment is an essential requirement of all cellular life. In certain bacterial pathogens, host-derived nutrients can be used for growth during infection but can also be used to enhance colonisation and virulence. Pathogens such as Haemophilus influenzae and Vibrio cholerae take up sialic acid from the host and can present it on the cell surface, which allows the bacteria to evade the innate immune response. Therefore, these sialic acid uptake routes are prime targets for the development of inhibitors to treat and prevent bacterial infection. In this project, we will interrogate the structure and mechanism of the sialic acid-specific TRAP transporter from H. influenzae. TRAP transporters have an extremely fascinating, but poorly understood mechanism, which employs a unique combination of an essential soluble substrate binding protein and a Na+-driven, elevator-like movement of the transmembrane domain to facilitate transport across the membrane. This project will probe the interaction of the substrate binding protein with the membrane component and assess the contribution of selected amino acids to the transport mechanism. To do this, we will use a combination of molecular biology, biochemical and microbiological approaches.

The path to least resistance: probing the mechanism of integral membrane transport proteins essential for antimicrobial resistance in bacteria
Supervisor: Dr Chris Mulligan
Course: Microbiology, Biochemistry, Cell Biology

Antimicrobial resistance is a major global health concern. One of the most effective mechanisms bacteria have developed to resist the effects of antimicrobial agents is to use drug efflux transporters to pump them out of the cell before they can do any damage. Understanding the structure and function of these proteins will lay the foundation for the development of future inhibitors, which could be used to enhance the efficacy of current antimicrobials and breathe new life into antimicrobials rendered ineffective due to the development of resistance. In this project, we will elucidate the functional mechanism of a family of integral membrane transport proteins that strongly influence the antibiotic resistance of several bacterial pathogens. This project will take an integrated approach to probing the structure and function of these membrane proteins, which will include protein biochemistry, biophysical approaches and microbial phenotypic assays.

Cancer Biology and Ageing


Understanding the sex-specific role of SKN-1B/Nrf in appetite regulation and metabolic health
Supervisor: Dr Jenny Tullet
Course: Cell Biology, Genetics

Our lab uses the nematode worm C. elegans to study a molecule called SKN-1B. This is a transcriptional regulator and the C. elegans homologue of the mammalian Nrf proteins. Recently we discovered that SKN-1B acts in specific neurons to controlling the feeding behaviours and metabolism of C. elegans. Moreover, SKN-1B seems to act differently in hermaphrodite compared to male animals. We have a number of ongoing projects in our lab suitable for Master’s level projects. We are examining the molecular function of SKN-1B and its interaction with other genes/molecules/signalling pathways, the neuronal circuits it employs, its metabolic impact on age-related health, and understanding how it works in a sex-specific manner. We use a combination of genetic tools (mutants, RNAi, CrispR), behavioural assays (exploration, satiety, chemotaxis), physiological tests (lipid/glycogen measurements, mitochondrial imaging), together with a variety of microscopy (light, confocal) and molecular techniques to answer these questions. Master’s projects are designed on a case-by-case basis to suit the interests of the student and the laboratory as a whole. Please do come and discuss these with me if you are interested.

Investigation of drug-adapted cancer cell lines
Supervisor: Professor Mark Wass and Professor Martin Michaelis
Course: Cell Biology

We host the Resistant Cancer Cell Line (RCCL) collection, the worldwide largest collection of drug-adapted cancer cell lines and models of acquired drug resistance in cancer at Kent. In this project, drug-adapted cancer cell lines will be characterised and investigated to gain novel insights into the processes underlying resistance formation and to identify novel therapy candidates (including biomarkers).

Using cancer genomics to identify biomarkers of cancer resistance
Supervisor: Professor Mark Wass and Professor Martin Michaelis
Course: Cell Biology

At Kent we host the Resistant Cancer Cell Line (RCCL) collection, the largest collection of cancer cell lines worldwide that have been adapted to anti-cancer drugs. These cells represent a model of drug resistance in tumours. This project will analyse exome sequencing data of a set of cell lines to identify mechanisms of resistance and biomarkers.

Cold-shock, translational reprogramming and development of treatments to prevent neurodegeneration and cancer
Supervisor: Dr Mark Smales
Course: Cell Biology, Biochemistry

With colleagues we have shown that mammalian cells respond to cold-shock by reprogramming protein synthesis, particularly by utilising transcripts with different codon usage. Some of these proteins whose synthesis is regulated can be neuroprotective. This project will look to further explore the mammalian responses to cold-shock and how these could be harnessed for the development of treatments in the clinic.

Cleaning up the rubbish in the cell: the role of the proteasome in healthy ageing
Supervisor: Dr Jerome Korzelius
Course: Genetics

Damaged proteins in the cell end up in the proteasome: the cell’s rubbish bin. The proteasome makes sure damaged proteins are properly broken up and recycled. If this does not happen, damaged proteins can aggregate and clog up the cell. In the brain for instance, this build-up of aggregated proteins is a leading cause of diseases like Alzheimer’s and dementia. Increased age is the major risk factor for these diseases due to the fact that the proteasome does not function properly anymore at advanced age. You will study the proteasome in different tissues and at different ages in the fruit fly (Drosophila melanogaster). We will use in vivo proximity labelling, that will label the proteasome and its interactors and identify regulators of this protein complex. In collaboration with Dr. Alessandro Ori (FLI-Leibniz institute on Aging, Germany), you will identify novel proteasome regulators that change with ageing and test these for their effect on proteasome function. Techniques include fly genetics, immunohistochemistry, protein purification and Western blotting.

Developing a novel therapeutic approach to treat cancer
Supervisor: Professor Michelle Garrett and Professor Jennifer Hiscock
Course: Cell Biology

Cancer kills over 160,000 people per year in the UK with 10-year survival being only 50%. Treatment includes chemotherapy and molecular targeted therapies, but often there is limited effectiveness due to inadequate cellular uptake. Supramolecular Self-associating Amphiphiles (SSAs, inventor Prof Jen Hiscock) are a new class of molecule that act as anticancer agents and enhancers of anticancer agent efficacy (doi: 10.1039/d1ra02281d). The aim of this MSc project is to investigate the use of newly developed SSAs to increase the efficacy of cancer drugs e.g. cisplatin and olaparib, in ovarian and/or bladder cancer cells and provide a route to clinical trial for SSAs in cancer patients. This project will be part of a wider ongoing collaboration between Garrett/Hiscock on the use of SSAs in cancer. Techniques that the student will learn include human cell culture, cell proliferation assays, western blot analysis , cell cycle analysis by flow cytometry and fluorescence microscopy.

Disease, Diagnostics and Therapeutics


Protein LAMPS: Shining a light on disease
Supervisor: Dr Dave Beal
Course: Biochemistry, Chemistry

Diagnostic devices are incredibly important tools in the control of disease. Whilst PCR based methods are excellent for sensitivity and exploring genetic changes, protein-based tools rely on enzymatic reactions, or the colour/fluorescence of molecules attached to targeting molecules i.e. antibodies. Isothermal amplification techniques are a new PCR based technique for the simple and effective detection of pathogens/disease states by looking for specific DNA/RNA sequences. In this project we will develop DNA/protein conjugation strategies to produce antibody DNA conjugates that can be developed for diagnostic purposes, Protein LAMPs. This project will focus on the production of these conjugates as well as an investigation of their sensitivity. Skill developed: Biochemistry, bioconjugation, analytical chemistry.

Wildlife Diagnostics
Supervisor: Dr Dave Beal
Partner: Biomolecular Diagnostics for Conservation Network Group
Course: Biochemistry, Chemistry

SARS CoV-2 highlighted the importance of diagnostics for the prevention of virus spread. Diagnostic tools are also incredibly important for the protection of wildlife on a local and global scale. The new Biomolecular Diagnostics for Conservation Network Group are looking students to develop projects focused on protecting wildlife and the environment. These include the development of rapid diagnostics for determination of the exposure of wild Amur Tigers and Leopards to Canine Distemper Virus (CDV), detection of avian influenza and the determination of pathogens/toxic chemicals in animal samples. This project is broad with many people interested in different aspects. This project would be ideal for students wanting to combine an interest in conservation with biochemistry/molecular biology and chemistry. Skills developed: Biochemistry, molecular biology, analytical chemistry.

Development of New Technologies for the Diagnostics Development
Supervisor: Dr Dave Beal
Course: Biochemistry, Chemistry

To protect public health, it is imperative to have diagnostic tools which are able to detect infection/disease rapidly. A key methodology in the production of diagnostics is bioconjugation, the process of attaching functionality, like a method of detection, to a targeting molecule like an antibody. Examples of these functionalities are gold nanoparticles for lateral flow assays and horseradish peroxidase for enzyme linked immunosorbent assay (ELISA). In this project we will develop new methodologies for the attachment of diagnostics tools to targeting molecules. This project with Prof. Mark Smales and Prof. Martin Warren will investigate Vitamin B12/BtuG conjugation or cobalt (III) mediated polyhistidine tag conjugation. Skills developed: Biochemistry, bioconjugation, analytical chemistry.

Development of diagnostics and potential vaccines for Mycoplasma bovis
Supervisor: Professor Mark Smales
Course: Biochemistry, Cell Biology

Mycoplasma bovis is a pathogen that is found globally in the bovine (cattle) population and results in respiratory disease and calf pneumonia. Antibiotic resistant strains are also emerging and this, along with the movement of cattle and people, a lack of a vaccine or low cost rapid diagnostic tests that can be used to monitor and detect the disease in the filed have combined to present a significant problem. This project will look to recombinantly produce Mycoplasma bovis antigens (proteins) so that they can be used in the development of rapid diagnostics for the presence of the pathogen in infected animals in the field and as potential vaccine candidates. The project will involve training in bioinformatics, molecular biology/cloning, recombinant protein expression, purification and characterisation and assay development.

New modalities and better design principles for RNA Therapeutics
Supervisor: Professor Tobias von der Haar
Course: Biochemistry, Cell Biology, Computational Biology, Genetics

The Covid vaccines were the first clinically approved RNA Therapeutics, and established that RNAs can be used to deliver therapeutic proteins into patient cells in the clinic. A wide portfolio of new RNA Therapeutics are now being proposed, including further vaccines, cancer therapeutics, protein replacement therapies for hereditary diseases, and many more. While RNA Therapeutics clearly work, they are also still very young and there is scope for developing the technology to enable new and different types of treatments, and to enter into new fields (for example, veterinary medicine). My lab is interested in developing the technology base for RNA Therapeutics, often by working with partners on specific products which we use to test how well our solutions work. As an MSc student in the lab you would explore and develop specific design ideas that emerge from this work, using approaches from biochemistry, cell biology and/ or computational biology.

Identifying bottlenecks in gene therapy delivery mechanisms and developing novel strategies to enhance AAV production
Supervisor: James Budge
Course: Biochemistry, Cell Biology, Genetics

Recent advances in gene editing and manipulation techniques have paved the way for exciting new gene therapies and it is estimated that over 2,000 gene-based medicines are currently undergoing various stages of clinical development. Whilst the future of gene therapies holds enormous potential, challenges still remain in this developing area. Current gene therapy delivery strategies such as adeno-associated virus (AAV) vectors have a limited DNA cargo size and have proved difficult to synthesise in existing hosts such as human embryonic kidney (HEK) cells. This project will use novel approaches to 1) enhance understanding of cellular processes which lead to constraints in production and delivery of gene therapies 2) develop new strategies to enhance AAV production in HEK cells.

Engineering Biology


Synthetic biology approach to self-assembled fibrous bio-materials for degradation of microplastics
Supervisor: Dr Wei-Feng Xue
Course: Biochemistry, Computational Biology

The aims for this project is to design and produce functional amyloid fibrils displaying a specific structural organisation or a selection of enzymes or small molecule/metal binding motifs, and to evaluate the structure and of these fibrils using cutting-edge AFM imaging analysis, as well as the designed function of these fibrils. Accumulation of microplastic waste in the environment is a costly and ongoing societal challenge that can potentially be addressed through the recent discovery of enzymes that are able to degrade Polyethylene terephthalate (PET) and recycle it into its constituent building blocks. However, no efficient materials applications currently exist that utilise these enzymes. This project will use a synthetic biology approach to engineer a novel biomaterial based on linking PET degrading enzymes onto functional amyloid fibrils. Amyloid fibrils are a type of protein structures with a characteristic fibrous shape. Some amyloid fibrils are well-known to be associated with diseases such as Alzheimer’s disease, Parkinson’s disease, and systemic amyloidosis. However, many amyloid structures are beneficial, or ‘functional’ in that they fill essential biological roles. We intend to functionalise amyloid fibrils and imbue them with PET degrading functionality in this project.

Understanding PROTAC metabolism
Supervisor: Dr Dave Beal and Professor Mark Smales
Partner: York Bio
Course: Biochemistry, Chemistry

Proteolysis Targeting Chimeras (PROTAC) are new class of therapeutic agent, which instead of inhibiting a specific enzyme like traditional drugs, are able to target them for degradation. These molecules have three parts, one which binds to the target of interest, one which targets a part of the proteasome and a linker to hold the two together. There is a wide variety of ways of producing these molecules and the aim of this project is understand which one is best. Working in conjunction with Yorkbio at Discovery Park we will focus on how different PROTACs are metabolised by the body. Skills Developed: Synthetic organic chemistry, analytical chemistry, biochemistry.

Production of Bifunctional Antibodies
Supervisor: Dr Dave Beal and Professor Mark Smales
Course: Biochemistry, Chemistry

Recombinant protein production has been an important innovation that has allowed antibodies to be utilised as therapeutic and diagnostic agents. The classic IgG molecule with two identical antigen binding domains is commonly produced in mammalian host cell systems. New innovations in the field have shown that bi and trispecific antibodies which can bind to different antigens are powerful new methodologies. Unfortunately, these molecules are much more difficult to make using cell-based production. In this project we will utilise a chemical linker to combine two and three different antibody fragments to produce novel bi and trifunctional antibody surrogates. This is an exciting project in the area of biotechnology. Skills developed: Biochemistry, bioconjugation, analytical chemistry.

Development of a Versatile Antibody for Drug Conjugate Production
Supervisor: Dr Dave Beal and Professor Mark Smales
Course: Biochemistry, Chemistry

Targeted therapeutics, or magic bullets, have been an important aim in drug discovery for a long time. Antibody Drug Conjugates (ADC) are a relatively new methodology that enable a drug molecule to be directed to a specific cell by the action of antibody targeting. These molecules have already had an impact in the clinic but still have some shortfalls in terms of side effects. A recent innovation in ADC development has been the production of poly-drug ADC, antibodies with different drugs attached. This technology requires site specific antibody modification and the use of trifunctional linkers. This project could look at 2 different aspects: the production of a enzymatically modified IgG molecule for attachment of drug molecules or the development of a trifunctional linker for attachment of the drug molecules. This is a really exciting project at the interface of chemistry and biology. Skills developed: Chemistry, biochemistry, molecular biology, analytical chemistry.

Development of Analytical Methods for Antibody Drug Conjugate Analysis
Supervisor: Dr Dave Beal and Professor Mark Smales
Partner: York Bio
Course: Biochemistry, Chemistry

Antibody drug conjugates (ADCs) combine both small molecule therapeutics and antibodies together into a single molecule. They are made by chemical modification of antibodies and, depending on method, can give rise to mixtures of products. It can be very difficult to analyse these structures which complicates their development. ADC usage in the pharmaceutical industry is expanding rapidly and analysis of them as a product as well as what happens to them when the body metabolises them is incredibly important. This project is a collaboration with Yorkbio at Discovery Park and will investigate chromatographic and mass spectrometry based analytical methods for the determination drug to antibody ratio and pharmacokinetics. Skills developed: Biochemistry, bioconjugation, analytical chemistry.

Generation of Coronavirus protein antigens, diagnostics and vaccines
Supervisor: Professor Mark Smales
Course: Biochemistry, Cell Biology

This project will build upon the on-going work to recombinantly produce key protein antigens from the coronavirus and then utilise these in diagnostics and the development of new vaccine candidates. Candidates will be involved in the cloning, expression and characterisation of the major protein components of the virus and various truncations and modifications thereof, and subsequent attachment of these to bacterial microcompartments such that these can be used to generate proof-of-concept data on the utility of this approach to elicit an appropriate immune response indicative of good vaccine candidates. Such technologies will also be explored for application into other areas of vaccine need in collaboration with colleagues in the UK and abroad.

Making Super Mammalian Cell Factories for the Production of Biological Drugs – Biotherapeutic Proteins and Gene Therapy Applications
Supervisor: Professor Mark Smales
Course: Biochemistry, Cell Biology

Mammalian cells are a major expression system for the production of biotherapeutic recombinant protein drugs used to treat a range of diseases and for the generation of gene therapies. The Chinese hamster ovary (CHO) cell is the current industrial system of choice for the expression of complex, post-translationally modified recombinant biopharmaceutical proteins for use in humans in the clinic to treat a variety of diseases. Current CHO host cells have been manipulated and ‘optimised’ for the commercial manufacture of monoclonal antibodies (mAbs) in particular, however many new protein biologics in development are difficult to express (DTE) in these systems. As such the product yields and quality are not sufficient to be used in the clinic and potentially life changing and saving drugs thus never reach the market. The programme of work here will take a novel approach to solving this challenge and provide a fundamental understanding of the impact of metabolic engineering on the CHO and HEK cell factories and their ability to produce biotherapeutic proteins and gene therapies at high yield and quality, particularly those that are DTE in CHO cells or any other system. The project will particularly involve training in molecular biology (particularly new approaches to cloning), protein analysis and characterisation, analytics, cell culture, genome/cell editing/engineering and microscopy.

Engineering the Microbiome of Black Soldier Fly Larvae for Regenerative Agricultural Practices
Supervisor: Dr Anastasios Tsaousis
Course: Microbiology

This project aims to explore and enhance the microbiome of Black Soldier Fly larvae to improve waste decomposition and nutrient cycling, pivotal for sustainable agricultural systems. By manipulating microbial communities within the larvae, the project seeks to increase the efficiency of organic and plastic waste conversion into valuable biomass, supporting regenerative agriculture. Techniques will include microbiome analysis, microbial genetic engineering, and experimental bioassays in controlled environments to assess impacts on waste degradation (including plastics) and nutrient profile improvements.

Enhancing a microbial solution to drastic plastic pollution
Supervisor: Dr Chris Mulligan
Course: Biochemistry

Phthalic acids (PA) are major constituents of plastics, acting as either part of the polymeric structure (e.g. in polyethylene terephthalate, PET) or as essential non-covalently associated plasticisers. PA plasticisers, which have carcinogenic properties, readily leach out of waste plastics leading to contamination of the environment, and are classified as major man-made priority pollutants due to their ability to cause ill health in both humans and animals. The development of microbes to take up and degrade PA plasticisers would provide a cost effective and environmentally friendly solution to this growing problem. A critically important step in this bioremediation process is the efficient transport of the PA plasticisers from the environment into the bacteria where they can be broken down. Microbial degradation of PA plasticisers removes these pollutants from the environment, but also provides the opportunity to use them as a feedstock for high value chemicals. In this project, we will interrogate the structure and mechanism of predicted bacterial PA transport proteins that are currently very poorly understood. To do this, we will use an integrated approach combining molecular biology, biochemical and biophysical analyses, and microbiological approaches. The goal of this project is to further our understanding of the PA uptake mechanisms that bacteria employ to remove this major pollutant from the environment.

Design, synthesis and evaluation of DNA tools for genetic engineering of mammalian cells
Supervisor: James Budge
Course: Biochemistry, Cell Biology, Genetics

DNA transposons, or “jumping genes”, are DNA sequences that are able to change their position within a genome in a ‘cut and paste’ mechanism called transposition. These systems have been harnessed to facilitate highly efficient stable insertion of DNA into a host genome with applications in biotechnology, researching diseases and gene and cell therapies. A major advantage to using transposase systems is their ability to integrate large DNA cargo (reportedly up to 200kb) into host cells. Synthetic biological circuits facilitate reprogramming of cellular behaviours; combining synthetic biological parts to induce logical functions where a desired output is dependent on a specific input. Such circuits have been designed and applied to biosensing and diagnostics, drug discovery and biotherapeutics. This project aims to develop and evaluate DNA tools based on transposon integration technology which will facilitate stable introduction of synthetic circuits and metabolic pathways into cultured mammalian cells. These tools will be instrumental in enhancing production of biotherapeutics and developing biosensors for diagnostic purposes.

Genomics, Evolution and Reproductive Biology


Understanding genome evolution in mammals
Supervisor: Dr Marta Fare Belmonte
Course: Computational Biology, Genetics

Most species, even closely related species, exhibit differences in terms of their chromosomes. This phenomenon, combined with the observation that chromosomal rearrangements can lead to a reduction in the fertility of heterozygous hybrids, suggests that chromosomal changes have the potential to drive speciation. However, how these changes occurred and its impact on species evolution is still unknown. In this project the student will focus on a type of chromosome rearrangement, Robertsonian fusions (Rbs), and will investigate the mechanism that led to this rearrangement. Combining long-read nanopore sequencing of animals with and without Rbs with bioinformatic analysis of the fusion points, the project aims to pinpoint to the mechanism of Rb fusions. In this project the student will gain expertise in state-of-the-art genomics and bioinformatics, two of the most sought-after skills in the workplace.

Evolution of the muscle sarcomere. A bioinformatics approach to the interaction between myosin and myosin binding protein-C
Supervisor: Professor Mark Wass
Course: Computational Biology, Genetics

Following on from a study of how muscle-type myosins have adapted, over evolutionary timescales, for different types of muscle contraction, we will explore the co-evolution of myosin and the myosin binding proteins C. MyBP-C is well known to carry mutations linked to inherited heart disease.

Integrated understanding of health


Nano-imaging and structural biology of amyloid assemblies at the individual molecular level
Supervisor: Dr Wei-Feng Xue
Course: Biochemistry, Computational Biology

A number of human disorders, for example Alzheimer’s disease (AD), Parkinson’s disease (PD), type 2 diabetes, and transmissible spongiform emcephalopathies (TSEs), are associated with the abnormal folding and assembly of proteins. The aim of this project is to identify and understand the structural organisation and structural polymorphism of amyloid aggregates using nano-scale imaging methods. This project will include training on atomic force microscopy (AFM) and electron microscopy (EM), and cutting-edge image analysis methods developed in the Xue laboratory.

In-cell structural biology: CLIC1 structure, function and drug binding inside tumour cells
Supervisor: Dr Jose Ortega Roldan
Course: Biochemistry

CLIC1 is a chloride channel that gets upregulated in different tumour cells and whose inhibition has been shown to halt tumour progression. Using a range of in-silicone, structural biology and cellular methods we have already been able to develop novel drugs that inhibit CLIC1 function in cancer cells. The aim of this project is to develop optimised inhibitors of CLIC1 function. The project would involved further characterisation of the activation and inhibition mechanisms with atomic detail using a range of structural biology techniques, including NMR, X-Ray crystallography and fluorescence microscopy.

Decoding Immune Dynamics: How Molecular Flexibility Shapes Disease Defense
Supervisor: Dr Jose Ortega Roldan
Course: Biochemistry

MHC-I molecules are key to immune defense, presenting protein fragments (peptides) to CD8+ T lymphocytes, which recognize and eliminate threats like viruses, bacteria, and tumors. The interaction between MHC-I and T-cell receptors (TCRs) determines immune responses. While structural biology has provided static images of these complexes, the role of dynamics in recognition remains unclear. Our research combines X-ray crystallography, which captures molecular structures, with solution NMR, which reveals how proteins move and adapt. By studying peptide flexibility and MHC-I conformational changes upon binding, we aim to understand how dynamics influence TCR recognition. This deeper insight could improve immunotherapy design, enabling more effective and universal treatments for diseases by optimising immune responses.

Investigating the role of chaperones in the stability and assembly of multi-protein complexes
Supervisor: Dr Mohinder Pal
Course: Biochemistry

Heat Shock Protein 90 (HSP90) is a molecular chaperone and is an essential protein for cell survival. It is involved in the folding and assembly of several proteins called clients of HSP90. Some of these client proteins cause several diseases in humans, such as cancer, making HSP90 a potent anti-cancer target. The interaction of HSP90 with its client proteins does not occur directly. Instead, it relies on helper proteins called “co-chaperones of HSP90”, which bind and recruit client proteins for their folding and assembly. Upon recognising the client proteins bound to its co-chaperone, HSP90 utilises its ATPase activity to facilitate the folding and activation of its clients. Despite the structural and biochemical work, it is still unknown how HSP90 interacts with a variety of its client proteins via its diverse co-chaperones. In these two projects, we will investigate how HSP90 interacts with and recognises its client protein presented by its co-chaperone. Research questions: In these two projects, we will investigate how HSP90 interacts with its co-chaperones when bound to different client proteins and how these clients are activated by HSP90 molecular chaperone? To answer these questions, we will employ biochemistry and structural biology techniques such as single particle cryo-electron microscopy (Cryo-EM) and X-ray crystallography to determine the three-dimension structure of HSP90 bound co-chaperone-client protein complexes at the highest possible resolution. The learning outcome for potential students: Students will learn protein over-expression using bacterial and eukaryotic expression systems. They will have hands-on biochemistry techniques such as affinity and size exclusion chromatography and protein-protein interaction studies using pull-down and Iso-thermal Titration Calorimetry (ITC). For structural work, students will learn X-ray crystallography and single-particle cryo-electron microscopy (Cryo-EM) techniques to determine high-resolution structures of multi-protein complexes.

Probing the mechanism of INDY (I’m not dead yet) transporters: a target for the treatment of cancer, diabetes and obesity
Supervisor: Dr Christopher Mulligan
Course: Biochemistry

In eukaryotic cells, disrupting the activity of INDY transporters can extend lifespan, reduce cancer cell proliferation, and protect against metabolic disease such as diabetes and obesity. To develop inhibitors for INDY proteins, we first need to understand their transport mechanism. In this project, we will investigate the mechanism of the bacterial representative of this family, VcINDY. We will probe substrate and inhibitor interactions, and proteins dynamics using biochemical and biophysical approaches. The student will receive training in molecular biology techniques, such as site-directed mutagenesis, integral membrane protein expression and purification, transporter characterisation, protein biochemistry and biophysical techniques.

The molecules underlying microbiome health benefits
Supervisor: Dr Marina Ezcurra
Course: Cell Biology, Microbiology, Genetics

The gut microbiome profoundly impacts human health, but how it does this is largely unknown.  Studies suggest that the microbiome acts through the transcription factor Nrf, a regulator of stress-responses, lifespan and appetite. A major challenge in studying host-microbiome interactions is the difficulty and cost of mammalian models and the complexity of the human microbiome. This project will use a simple and versatile organism C. elegans to explore the molecular basis of the gut-brain-axis by which the microbiome and Nrf impact health. Training: Microbiology, molecular-biology, immunology, biochemistry, microscopy, genetics, bioinformatics.

Sustainable agriculture and food


Jumping Genes: How Transposons and Small RNAs Shape Plant Development
Supervisor: Dr Sara Lopez-Gomollon
Course: Biochemistry, Cell Biology, Genetics

Cells with identical genomes can differentiate into distinct cell types through differential gene expression. Transposable elements (TEs) play a key role in this process by altering gene expression when they insert into genes. Some TEs are activated during development, and our research shows that they can be processed into small RNAs, which regulate gene expression. In petunia, specific TEs cause visible changes in flower colour patterns. These TEs are processed into small RNAs by the RNA silencing machinery. During this master’s project, you will explore how transposons and their derived small RNAs regulate gene expression in plant development. You will use Next-Generation Sequencing techniques like sRNA-seq, molecular biology methods, and bioinformatics tools. Your research will contribute to understanding plant development and highlight the genetic roles of transposons, often considered “junk DNA,” with potential applications in agricultural biotechnology.

More info in references: PMID: 35597968; PMID: 35710830, PMCID: 7496347

Decoding Dormant Viruses: A Path to Food Security
Supervisor: Dr Sara Lopez-Gomollon
Course: Biochemistry, Cell Biology, Genetics

By the end of the century, global temperatures are expected to rise by 3.5°C, leading to a 10% reduction in crop yields per degree increase. This, combined with the threat of new pathogens, poses a major food security challenge. Plants harbour dormant viruses known as Endogenous Pararetroviruses (EPRVs), which can be activated by abiotic stress, potentially causing viral diseases. The specific conditions leading to EPRV activation are not fully understood, but plants defend against these infections by activating RNA silencing to cleave viral RNA into small RNAs. Our group recently discovered that these small RNAs are precisely 22 nucleotides long. During this project, you will analyse publicly available datasets to identify EPRV-derived 22-nucleotide small RNAs as a proxy for viral activation. This research will help identify the conditions under which EPRVs are activated, providing insights into how to develop strategies to control viral infections in crops, ensuring food security.

More info in references: PMID: 35597968; PMID: 35710830

Waking Up Dormant Viruses: A Synthetic Biology Approach to Plant Immunity
Supervisor: Dr Sara Lopez-Gomollon
Course: Biochemistry, Cell Biology, Genetics

Plants harbour dormant viruses called Endogenous Pararetroviruses (EPRVs), which can be activated under stress, potentially leading to viral diseases. The plant immune response involves RNA silencing, where viral RNA is cleaved into small RNAs. Our research identified Dicer-like 2 (DCL2) as the protein involved in this process, but how it specifically recognizes viral RNA is still unclear. During this master’s project, you will develop an inducible system to activate EPRVs on demand, using synthetic biology techniques. This ON-OFF mechanism will allow you to study viral activation independently of environmental stress. You will use this system in tomato plants to investigate other proteins involved in the viral response, monitor EPRV cleavage through fluorescence, and employ molecular biology, proteomics, and microscopy. This research will advance our understanding of plant immunity, helping develop strategies to protect crops from viral infections, with a significant impact on food security. More info in references: PMID: 35597968; PMID: 35710830.

Seaweed-Based Biostimulants for Sustainable Agriculture
Supervisor: Dr Sara Lopez-Gomollon
Course: Biochemistry, Cell Biology, Genetics

The overuse of chemical fertilizers in agriculture poses significant environmental risks, including soil degradation and water pollution. This project explores the potential of seaweed-based biostimulants as a sustainable alternative to enhance plant growth and resilience while improving soil health. By investigating how seaweed extracts influence seed germination, plant development, and stress tolerance, this research aims to reduce dependency on synthetic inputs, aligning with global sustainability goals. The project will involve a combination of physiological assessments and molecular techniques, such as gene expression analysis, to understand the underlying mechanisms of seaweed’s beneficial effects. Through this research, the student will gain valuable skills in experimental design, data analysis, and advanced plant science techniques, preparing them for a scientific career while addressing critical global challenges. More info in references: PMID: 36294984, PMID: 35360501

Boosting Plant Disease Resistance Through RNAi
Supervisor: Dr Helen Cockerton
Course: Computational Biology, Microbiology, Genetics

Plant pathogens can cause extensive damage to crops, and if left untreated, epidemics can lead to complete crop destruction. Host Induced Gene Silencing (HIGS) can be used to provide an environmentally friendly strategy for disease control. Through this project we will study the efficacy of HIGS through the construction of vectors containing hairpins that target plant pathogen genes. These vectors will then be transformed into the model plant Arabidopsis and pathogenicity assays will be conducted with two fungal pathogens (Botrytis and Verticillium) in order to assess the disease resistance status of Arabidopsis mutants.

Determining the mechanism of genotype specific AMF colonisation in strawberry
Supervisor: Dr Helen Cockerton and Dr Gary Robinson
Course: Computational Biology, Microbiology, Genetics

Arbuscular mycorrhizae fungi (AMF) colonies the roots of plants and provide nutrients in exchange for carbon. AMF are able to protect strawberry plants from drought stress and boost yields in low nutrient environments. Two cultivars of strawberry have been shown to have contrasting root system architecture. You will investigate the relative propensity of these cultivars to form mycorrhizal associations, in tissue culture and soil less substrate. You will then study the plasticity of root system architecture of the strawberry cultivars when grown in low and high nutrient environments and determine the impact of nutrient level on mycorrhizal association and root system architecture. Although largely aseptic we will also examine any associated microbiome and the metabolome of the rhizosphere in each cultivar. This project will require quantification of AMF levels both through microscopy and qPCR, supplemented with 16S amplicon sequencing and rhizosphere quantification by extraction and analysis.

Understanding the rules of life


Monitoring the Microbiome of Ruminants Colonised by Eukaryotic Microbes
Supervisor: Dr Anastasios Tsaousis
Course: Computational Biology, Microbiology

This research will focus on characterising and monitoring the microbiome dynamics in ruminants infected with eukaryotic microbes, such as protozoa and fungi. The project will investigate how these microbes influence the gut microbiome’s structure and function, potentially affecting host health and productivity. Methods will include next-generation sequencing, microbial culturing, and in vivo experiments to evaluate microbiome stability and its impact on digestive efficiency and immune response.

Long-term Colonization of Microbial Parasites in Animals at Wildwood Trust Zoo
Supervisor: Dr Anastasios Tsaousis
Course: Computational Biology, Microbiology

This project will examine the long-term effects of microbial parasites on host populations in a controlled conservation setting. By focusing on animals housed at the Wildwood Trust Zoo, the study will track changes in health, behaviour, and microbiome composition associated with parasite colonisation. The project will use longitudinal monitoring, parasitological examinations, and microbiome profiling to understand parasite-host interactions’ ecological and health implications in a wildlife conservation context.