We are excited to offer a number of PhD projects with supervisors at Kent as part of the South Coast Biology Doctoral Training Partnership (SoCoBio DTP).
These projects are divided into standard studentships and CASE studentships – the main difference being that the CASE studentships will involve a short period (~3months) based in an industrial company. If you are interested in any project we suggest you speak to the academic supervisors. Further information on eligibility, and how to apply can be found here.
Primary Supervisor: Professor Dan Mulvihill
Supramolecular Self-associating Amphiphiles are a new class of molecule invented by J. Hiscock, and developed collaboratively with D. Mulvihill, which exhibit multifaceted antimicrobial functionality, and are now ready to be developed out of the lab to have a real world use with your help.
Primary Supervisor: Dr Rebecca Hall
Filamentous fungi of the order Mucorales are ubiquitous in the environment and their spores are easily spread by aerosols leading to contamination of food products like soft fruits and vegetables. It is estimated that fungal contamination can result in a loss of up to 50% of some food products. In addition to causing food spoilage, fungi also secrete toxins that can cause sickness if contaminated food is consumed. Therefore, preventing fungal growth and contamination is essential to decrease the rate of spoilage of these food products. However, many of these fungi are resistant to commercially used antifungals, indicating that a novel approach to eradicate these fungi is required.
This project will identify soluble chemical mediators that have the potential to be used post-harvest to protect against fungal spoilage. The discovery of such molecules has the potential to have a large impact on food sustainability.
Primary Supervisor: Dr Campbell Gourlay
Amyotrophic lateral sclerosis, also known as motor neurone disease (MND) is a devastating and incurable disease. Significant research efforts have increased our understanding of the cellular dysfunction that underpins ALS pathology, but we have much to learn. Recent findings suggest that metabolic defects play an important role in the onset and progression of ALS, offering the tantalising prospect of new avenues to therapy. The project is multi-disciplinary and offers training in a wide range of cutting edge cell biological, microbiological, computational and biochemical techniques within the labs of Dr. Campbell Gourlay (Kent) and Prof. Majid Hafezparast (Sussex). The outcomes of this research will lead to a significant increase in our understanding of the metabolic dysfunction associated with ALS.
Primary Supervisor: Dr. Andrew Lawrence
Enzymes from the B12-dependent radical SAM (rSAM) superfamily catalyse wide ranging and chemically challenging reactions, including the methylation of unactivated carbon centres. They have emerged as significant players in the biosynthesis of many important natural products from bacteriochlorophyll to many antibiotics and anticancer agents such as pactamycin, mitomycin C, fosfomycin, polytheonamide and quinomycin. Despite their importance they remain poorly characterised.
The aim of this project is to purify and characterise a selection of B12-dependent rSAM enzymes involved in the biosynthesis of vitamins and antibiotics. The project spans synthetic biology and structural biology and a broad training will be provided in molecular biology, microbiology, protein purification, enzymology, structural biology and handling oxygen sensitive proteins and reagents. The successful candidate will be expected to spend time at both institutions, with 1 year of the project being based at the University of Southampton.
Primary Supervisor:Dr Simon Moore
Agriculture is worth about £24 billion to the UK bioeconomy, but it is threatened by rising levels of pest resistance, through to global warming and extreme conditions. Synthetic biology aims to design and engineer new life, using standardised parts and devices tested through the design-build-test-learn cycle approach.
This project aims to engineer symbiotic Streptomyces soil strains to release growth-stimulating factors and antimicrobials, to stimulate growth and eliminate disease threats, respectively. This project will study the potential of synthetic biology to engineer wild symbiotic Streptomyces bacteria with value-added potential to benefit growth and resist invasive pathogens.
Primary Supervisor: Dr Mark Wass
Viruses pose a continuous threat to humans, animals and plants. The threat to humans is currently illustrated by SARS-CoV-2, but there are many others as well. With advances in sequencing technologies the genome sequence of viruses can now easily be obtained, however understanding the virus biology is much more difficult. This proposal will further develop a methodology for the comparative analysis of related viruses displaying different phenotypes, which Wass and Michaelis have established over the last six years (Sci Rep 2016;6:23743).
Given the threat to human, animal and plant health posed by viruses it is essential that methods, in particular those that make efficient use of the increasing amount of sequencing data, are developed to enhance our understanding of virus biology and pathogenicity. This project therefore has the potential for far reaching impact across the biological sciences as it will enable our DCP approach to be generally applied by the scientific community to any type of virus.
Primary Supervisor: Dr Wei-Feng Xue
Amyloid fibrils are highly polymorphic structures formed by many different protein sequences. They provide biological functions but also abnormally accumulate in numerous human diseases such as Alzheimer’s and Parkinson’s diseases. The physical principles of amyloid polymorphism are not understood due to lack of structural insights at the single-fibril level. To understand the fundamental origins of fibril polymorphs and to quantify the level of heterogeneity is essential to decipher the precise links between amyloid structures and their functional and disease associated properties such as toxicity, strains, propagation and spreading. This project will produce a systematic series of short peptide sequences originating from a range of disease associated and functional amyloidogenic proteins, designed with systematically varied amino acid sequences and peptide length.
Primary Supervisor: Dr. Jerome Korzelius
Ageing involves the functional decline of cells, tissues and organs over time, leading to disease and death.Loss of proteostasis, the balance between the synthesis and degradation of proteins, is a hallmark of ageing and plays a causal role in many age-associated diseases, such as Alzheimer’s and Parkinson’s disease. The protein complex known as the proteasome plays a key role in maintaining proteostasis via selective degradation of damaged and unwanted proteins.
Our recent work highlighted a crucial role of the proteasome in brain ageing. However, how proteasome composition and its interaction with other proteins change with aging remains largely unknown. In this project, we will monitor proteasome composition and interactions in vivo in the fruit fly Drosophila melanogaster.
Primary Supervisor: Professor Michelle Garrett
Supramolecular Self-associating Amphiphiles (SSAs) are an exciting new class of molecule invented by JH (patent No. PCT/EP2018/069568) that have previously been shown to self-assemble and demonstrate activity as broad-spectrum antimicrobials and antimicrobial adjuvants. Excitingly, we now have preliminary data that shows at low non-cytotoxic concentrations, some SSAs can also enhance the anticancer activity of cisplatin in ovarian cancer cells.
The project aims to identify the mechanism by which SSAs enhance cisplatin activity; determine if this activity is can be extended to other classes of cancer drugs; and understand/develop/assess the structure activity relationship (SAR) of SSAs as next generation enhancers of current cancer treatments.
Primary Supervisor: Dr Christopher Mulligan
The alarming global progression of antimicrobial resistance threatens to propel humankind into a post-antibiotic era where illnesses and injuries that are currently trivial to treat become life-threatening conditions.
Even now, in the EU alone there are ~25,000 deaths per year directly associated with drug resistant bacteria. Unchecked, the global death toll could exceed 10 million deaths per year by 2050, even exceeding cancer-related deaths.
Developing new antibiotics is essential, but this is slow and expensive, and the chances of bacteria developing resistance to these new drugs is high. An extremely promising, complementary approach to help combat resistance is to reduce resistance itself. By identifying pathways that, when disrupted, sensitise resistant bacteria to antibiotics, we could breathe new life into drugs rendered obsolete, and boost the potency of newly developed drugs. In this project, we will use a multipronged approach to illuminate the physiological role of the DedA family.
Primary Supervisor: Ben Goult
This project aims to test a novel theory for how memories might be stored in the brain. Our research has identified a, previously unrecognised, expansive network of mechanical binary switches that are built into each and every synapse that we hypothesise have the potential to store information, and to alter the synaptic impedance to allow control of synaptic activity.
This project will provide the PhD student with a cutting-edge multidisciplinary training in biophysics and biochemistry (Goult) with cellular assays and neuroscience of synapse function (Staras) to test the hypothesis that synaptic signalling drives changes in the conformational patterns of the synaptic scaffold protein talin in a way that encodes information. Successful completion of this project will establish a new paradigm for how information is stored and processed in the brain.
Primary Supervisor: Dr Marta Farré
Structural genomic variants (SVs) have been studied going back to the discovery of chromosomal inversions in Drosophila in the early 20th century.
In this project, the student will develop a new approach to detect SVs in plant and animal genomes using state-of-the-art long-read Oxford Nanopore sequencing. This project will not only produce important biological insights, the methodology developed during this project will have a great impact in the agricultural and farm sectors by being able to detect SVs in a rapid and affordable manner for livestock and horticultural species.
Primary Supervisor: Professor Adrian Podoleanu
As a barrier to moisture loss, the epidermis and epicuticular waxes play a critical role in maintaining cell turgor while providing structural support combined with plasticity to respond to pressures associated with fruit expansion during development and ripening.
Access to non-destructive hand held devices that afford greater granularity in defining changes in cell turgor, wax deposition and vascular connectivity during develop will help shape future breeding and selection of fruit and vegetables by providing a better understanding of how epidermal cells respond to changes in the rate of fruit expansion and then shrinkage after harvest.
Primary Supervisor: Dr Jenny Tullet
Over-eating can lead to serious health complications So understanding satiety regulation (when to stop eating) is important. This project focuses on how these biological decisions work so that they can be harnessed to improve human health and fitness.
This project uses a variety of techniques: genetics, behavioural assays, molecular biology, and a variety of microscopy (including confocal and TEM) to delve into the underlying genetic and biological processes involved. The student will map the neuronal circuits, identify novel genetic interactors of SKN-1, and fully explore the physiological effects of disrupted satiety. As Nrf is expressed in regions of the mammalian brain important for regulating food-related behaviour, this project will provide a step change in the way we view Nrf function.
Primary Supervisor: Gary Robinson
The composition and influence of the microbiome has become a major focus of research in many areas of biomedicine in humans and many other species.
Different microbes within the microbiome may modify their environment (e.g. maintain a lower pH – Lactobacilli) or produce compounds that are bioactive (e.g. antimicrobials such as Streptomyces) therefore perturbing host processes. Understanding the normal and abnormal reproductive microbiomes and their effects on sperm function is likely to lead to diagnostic and treatment breakthroughs for both natural and assisted reproduction. Such insights can be extended to microbial bioactives (i.e. potential contraceptives or fertility supplements) that affect factors such as sperm motility and physiology.
This study will be facilitated by a newly-established diagnostic suite within the School of Biosciences capable of studying sperm vitality, motility, DNA fragmentation and DNA oxidation.
Primary Supervisor: Dr Marina Ezcurra
Recent research suggests that gut microbes can affect many aspects of human physiology, including function of the brain, impacting cognitive function, mental health and neurodegenerative diseases. Understanding the mechanisms underlying host-microbiome effects on the brain can result in the development of interventions to improve neuronal health.
To accelerate this line of research and identify novel bacterial molecules with beneficial effects on health, the Ezcurra lab uses a new model system to study host-microbiome interactions using the model organism C. elegans combined with an experimental microbiome. This model enables us to address important questions about how the microbiome affects host health in a way that is difficult to do in mammalian model systems. Magnitude Biosciences has developed high-throughput automated approaches to monitor C. elegans health beyond the capacity of traditional academic labs. The combined expertise and approaches of the Ezcurra lab and Magnitude Biosciences enables a unique innovative academic-industrial collaboration with the goal to identify microbiome-based interventions with translational potential to promote health of the nervous system.
Primary Supervisor: Peter Ellis
Developing germ cells within the testis show a suite of unusual characteristics, including high proliferation rates in pre-meiotic spermatogonia, genome-wide genetic rearrangement and tolerance to DNA damage in spermatocytes, and extensive cellular remodelling and metabolic rewiring in post-meiotic spermatids.
These aspects of germ cell biology must be tightly regulated in order to keep cell division in check and prevent harmful over-proliferation. Preliminary research in our laboratory suggests that in some cases, virus infection may induce a limited soma/germline transition that alters cell division checkpoints and facilitates survival. In other words, these viruses hijack elements of the meiotic programme to drive their own proliferation. This in turn may lead to cancer formation since the normal safeguards on cell division have been bypassed.
This project represents an interdisciplinary collaboration between reproductive medicine, cancer and bioinformatics groups. While the principal outcomes here are a better understanding of the basic science of how meiotic genes act when wrongfully expressed in non-meiotic cell types, there are also potential downstream applications in both diagnosis and treatment of malignancies.
If you require more information about the SoCoBio DTP and how to apply, please contact the academic leads from Kent:
Prof Colin Robinson: C.Robinsonemail@example.com
Dr Jenny Tullet: firstname.lastname@example.org