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We have a range of exciting and diverse PhD projects at our 3 partner university institutions of Birmingham (UoB), Leicester (UoL) and Nottingham (UoN) which are now open for application for a September 2024 start.
Projects with an industry partner (iCASE projects) offer a unique opportunity to undertake translational research.
The deadline for submitting applications is midday (GMT) Friday 12 January 2024. Please ensure that your application is submitted with all required documentation as incomplete applications will not be considered. Applications should include:
- completed application form
- a CV consisting of no more than 2 sides of A4
- a transcript of module marks
- completed ED&I form
Shortlisted applicants will be contacted by 9 February 2024 via email. If you don’t receive an email by this date then your application has not been shortlisted and you will not be invited for interview. Unfortunately, due to the number of applications the DTP receives, we will not be able to provide feedback on unsuccessful applications.
Interviews will take place during the week commencing 26 February 2024 and will be held via Zoom. Please ensure you are available for the whole week as if you are invited for interview, we are unable to offer any alternative interview dates/time. Candidate who are invited for interview/on the interview reserve list will be invited to an online interview information session with the DTP Leads/student representatives which will take place 14:30 – 15:30 (GMT) Friday 16 February 2024.
We strongly encourage you to contact the supervisor(s) of the project(s) you are interested in before submitting an application.
Due to stipulations from the funders, recruitment for international candidates to the DTP is capped at 30% of the whole cohort.
Applicants must hold, or be about to obtain, a First or Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in a relevant subject. A master’s qualification in a related area could be beneficial, as could additional relevant research experience.
More details can be found on the MRC website
The DTP Leads are holding two applicant webinars for prospective candidates interested in applying to the DTP on Monday 11 December at 18:30 GMT and Wednesday 13 December 2023 at 11:00 GMT. Both sessions will last no longer than 1 hour and will be held via Zoom. If you are thinking of applying to the DTP, you are encouraged to attend one of these sessions. As well as having the opportunity to ask questions, the session will provide information on the application process as well as information about the AIM DTP.
If you are interested in attending the webinar on Monday 11 December please complete the short registration form available here before 16:00 (GMT) 11 December.
If you are interested in attending the webinar on Wednesday 13 December please complete the short registration form available here before midnight (GMT) 12 December.
How to apply
Applications should include:
- completed application form
- a CV consisting of no more than 2 sides of A4
- a transcript of module marks
- completed ED&I form
You may apply for a maximum of 3 projects.
Birmingham applications to be submitted to firstname.lastname@example.org
Nottingham applications to be submitted to email@example.com
Applications need to be submitted by midday (GMT) Friday 12 January 2024. Late applications will not be considered and will not be responded to.
What happens after you have submitted your application?
After the closing date, midday (GMT) Friday 12 January 2024., the project supervisors will review all applications submitted for their project and shortlist a maximum of two candidates for interview.
Shortlisted applicants will be contacted by 9 February 2024 via email. If you don’t receive an email by this date then your application has not been shortlisted and you will not be invited for interview. Unfortunately, due to the number of applications the DTP receives, we will not be able to provide feedback on unsuccessful applications.
Shortlisted candidates will then be invited for interview during the week commencing 26 February 2024. Please ensure you are available for the whole week as if you are invited for interview, we are unable to offer any alternative interview dates/time.
Candidates who are ranked highest at interview will be offered a place on the DTP and will be recommended for the PhD position. Successful candidates will then be sent details of how to make the formal application at the project host institution and will be subject to standard admissions checks which is standard procedure. The host institution admissions team will then send out formal offer letters and details of how to complete the registration process.
Our available projects are detailed below.
Prof Laura Gray (UoL), Dr Joie Ensor (UoB), Dr Lucy Teece (UoL) and Prof Kamlesh Khunti (UoL)
This exciting project aims to update the Diabetes UK “Know your Risk” tool (https://riskscore.diabetes.org.uk/start) which is based on the Leicester Diabetes Risk Score. This tool asks for information about seven risk factors and assigns points to each answer, the total score reflects the individual’s risk of having undiagnosed type 2 diabetes or prediabetes. It is recommended that those with a high score visit their doctor for a diabetes test. Early identification of diabetes promotes early treatment, improving health outcomes.
This project looks to update the Leicester Diabetes Risk Score by:
- Reviewing published validations and updates of the score and assessing their performance.
- Assessing potential updates to the score algorithm and the risk factors included.
- Validating the score using primary care data.
This project is part of an exciting collaboration with the University of Birmingham, with supervisors based at both institutions. The student undertaking this project will have the opportunity to use their statistical skills to make improvements to this tool, impacting care and improving outcomes for people at risk of diabetes. This project would suit someone with a mathematical background. This opportunity will give skills in systematic reviewing, risk prediction modelling, and using real-world data.
Prof Chris Bayliss (UoL), Dr Chris Holmes (UoL), Prof Luisa Martinez-Pomares (UoN) and Prof Chris Brightling (UoL)
Non-typeable Haemophilus influenzae (NTHi) significantly contribute to human disease including chronic obstructive pulmonary disorder (COPD). This complex disease involves numerous host immune modulators. Replication of NTHi bacteria in the diseased lung is associated with chronic disease but it is not clear how these bacteria survive host immune responses. Multiple NTHi genes undergo rapid ON and OFF switching, called phase variation (PV), due to hypermutable repetitive DNA tracts. Two phase-variable genes drive addition of negatively (sialic acid) and positively (phosphorylcholine) charged epitopes onto the lipooligosaccharide. These molecules influence bacterial interactions with host immune cells. This project focuses on investigating how PV affects immune evasion in model systems and clinical samples from chronic disease patients. Led by Prof. Chris Bayliss and Dr. Chris Holmes, molecular approaches will be utilized to monitor whether NTHi PV facilitates immune evasion. Immunological assays, such as resistance to neutrophils, will be developed during sessions at the University of Nottingham with Prof. Luisa Martinez-Pomares. Analysis of clinical COPD samples will be overseen by Prof. Chris Brightling. These studies will help explain the extent to which PV of surface molecules underlies elicitation of host immune responses and ability of NTHi to survive and cause inflammation in complex chronic diseases.
Dr Shin-Yi Chloe Chiou (UoB), Prof Ales Holobar, Prof Zubair Ahmed (UoB), Prof Dario Farina (ICL) and Dr Paul Strutton (ICL)
Spinal cord injury (SCI) has significant impact on patients’ physical and psychological well-being. There are an estimated 1.2 million new cases worldwide each year. Such injuries disrupt the communication between the brain and body, causing loss of motor function below the injury. In the early stages following injury, repair processes are extensive in the spinal cord to restore these communication channels. Studies in rodents with SCI showed injury-induced axonal sprouting and functional recovery. With advanced technology, we are now able to measure axonal sprouting and reinnervation in human SCI using non-invasive high-density surface electromyography (HDEMG) system. Paraspinal muscles are directly innervated by the spinal nerves near the spinal cord where the injury is. We hypothesise that properties and behaviours of motor unit action potentials in the paraspinal muscles, assessed via HDEMG, in human with SCI can reveal the repair processes in the spinal circuits and predict outcomes of recovery. The project offers research training in a variety of techniques and methods, clinical training, and research networks across institutions nationally and internationally. The supervisory team provides divers expertise; the host institution is a leading research-intensive University in the UK. The student will be well supported and developed through the programme.
Prof Andrea Cooper (UoL), Dr Helen McGettrick (UoB) and Dr John Pearl (UoL)
In this exciting joint PhD project between the University of Leicester (UoL) and the University of Birmingham (UoB), the student will join a collegiate international consortium investigating lung immunity to tuberculosis (TB) and driving innovation in the TB vaccine pipeline. Development of an effective vaccine is the single most effective tool to reduce the worldwide TB. The multi-million Euro consortium brings together fundamental immunologists, clinical specialists, experts in non-human primate models and vaccine developers and manufacturers. The student will investigate the fundamental aspects of immune protection using immunology, immunohistology, flow cytometry, bioinformatics analysis and will learn in vivo imaging and spatial transcriptomics. The project will focus on the the ability of T cells to undertake adhesion and migration into the lung of TB-infected mice (UoL). At UoB, multi-cellular in vitro models of leucocyte adhesion and migration will used to dissect the role of specific molecules in T cell migration. A unique aspect of this studentship is the ability to undertake in vitro and in vivo models in the context of complementary human and non-human primate data. This is a super opportunity because of the range of techniques and approaches, the networking and the potential for internationalization of the student’s experience.
Prof Joao Pedro de Magalhaes (UoB) and Dr Amanda Sardeli (UoB)
Ageing is arguably the major biomedical challenge of the 21st century with the incidence of age-related diseases expected to increase dramatically in the coming decades. Interventions that extend lifespan and healthspan, and protect against ageing diseases, are therefore of immense interest. Given the intrinsic difficulties and costs of performing ageing studies in humans and even in mammalian animal models, however, developing predictive bioinformatics methods is of utmost importance.
In this project we aim to employ a machine learning approach to predict, among existing drugs, which ones have the greatest probability of being suitable for retarding human ageing and for targeting age-related diseases. As such, we will identify new drugs with potential for targeting ageing and age-related diseases and predict those with the greatest potential for human translation. Follow-up will be performed in human cohorts, such as UK Biobank. Moreover, worms and human cells may be employed for the experimental validation of the machine learning findings in this project.
Overall, this project will potentially accelerate the development of medicines for ageing diseases and open opportunities for future translational research.
This is a highly multidisciplinary and collaborative project involving computational biologists and experimentalists, providing a rich and diverse training in several state-of-the-art methods.
Dr Amy Naylor (UoB) and Prof Liam Grover (UoB) with Dr Katie Hansel and Dr Gareth Davies from industrial partner AstraZeneca
Worldwide, populations are aging. The risk of osteoporosis increases with age and currently ~200 million people are affected. Osteoporosis is characterised by bone weakening, resulting in fractures that reduce patients’ quality of life and independence and can be life-threatening. Therapeutic drugs that can increase bone mass are badly needed.
High-throughput screening (HTS) is the proven cornerstone of drug discovery. To identify compounds that translate into effective therapeutic drugs, HTS-assays must be as biologically relevant as possible. We have developed a biologically relevant bone cell-culture system. By combining cutting-edge biology and materials science knowledge from the University of Birmingham (3D bio-printing, transcriptomics, proteomics, metabolomics, and cell imaging technologies) with a placement at a state-of-the-art HTS robotics facility, you will miniaturise and optimise this system and use it to screen novel compound libraries to search for active molecules that could become the next generation of therapeutics.
This PhD project will provide training in cutting-edge “omics” technologies including metabolomics and proteomics. In addition, you will develop expertise in bioinformatics/coding, materials science, cell biology and high-throughput screening (HTS) robotics automation platforms. The project is part of a doctoral training programme, ensuring broader training and transferable skills are embedded in the PhD experience.
Prof Bethan Phillips (UoN), Prof Leigh Breen (UoB)_, Prof Jon Lund (UoN) and Dr Eleanor Jones (UoN)
Following surgery for cancer, older patients lose significant muscle mass and function due to the physiological insult of surgery and physical inactivity in the postoperative period. These losses cause delayed recovery from surgery and return to normal activities and are associated with significant physical and psychological upset. Although exercise rehabilitation after surgery is recommended, and sometimes delivered, this does not begin until the surgical wound has healed- several weeks after surgery. Similarly, although exercise prehabilitation has shown great potential, many older adults are unable to complete this. Emerging evidence suggests that a single bout of resistance exercise (sRET) before surgery may have potential to reduce postoperative losses of muscle mass and function in older cancer patients. However, how this strategy may be optimised, including interactions with nutrition is not yet known. This PhD will use state-of-the-art mass-spectrometry and novel imaging techniques to: i) identify the best form of sRET to promote muscle anabolism during subsequent immobilisation; ii) determine the impact of adjuvant protein nutrition on sRET-induced anabolism; and iii) determine the impact of optimised sRET in older colorectal cancer patients. This project will provide the successful candidate with varied skills and experience across the translational research pathway (i.e., bench-to-bedside).
Prof David Withers (UoB) and Dr Rebecca Drummond (UoB) with Dr Simon Dovedi from industrial partner AstraZeneca
We now understand that manipulation of the immune response can drive curative treatment of cancer. However, currently licenced immunotherapies only work in some patients. In colorectal cancer, the UK’s second most common cancer type, the vast majority of patients fail to benefit from these treatments. This failure appears to reflect the presence of numerous inhibitory mechanisms acting within the tumour microenvironment to impede the T cell response from becoming established. The solution probably lies in combinatorial therapies where multiple inhibitory pathways within the cancer can be targeted in concert. This PhD studentship is focused on interrogating some of the key inhibitory mechanisms that block the immune response in colorectal cancer and then investigating combination therapies designed to overcome them. To achieve this, cutting-edge in vivo approaches will be combined with the most physiologically-relevant colorectal cancer models to generate a new level of insight. This studentship will provide extensive training in cancer immunology, bioinformatics and the use of novel in vivo models at the forefront of tracking immune responses in tumours. Furthermore, through working closely with leading experts at AstraZeneca, this studentship will bridge fundamental cancer immunology research with experience of how industry seeks to progress the next generation of immunotherapies.
Prof Bindi Brook (UoN), Dr Amanda Tatler (UoN), Dr Jinming Duan (UoB) and Prof Ian Sayers (UoN)
One of the key characteristics of asthma is the irreversible structural changes that occur in the airway wall, termed airway remodelling. This typically consists of increased amounts of airway smooth muscle and increased extracellular matrix among other changes. Recent evidence suggests that forces transmitted by contracting smooth muscle cells to airway tissue can activate growth factors that cause airway remodelling in asthmatics, worsening the condition. The link between tissue mechanics and biology in vivo is not well understood but is key to developing a complete understanding of airway remodelling. In this project we will bring together an experimental ex vivo model called precision-cut lung-slice (PCLS; in which cells maintain their contractile ability in their native environment) with histological staining (to identify different cell types and proteins), machine learning to enable automatic detection of airway constituents from stained PCLS, spatial transcriptomics and predictive mathematical models to predict sites of growth factor activation within the airway wall. You will join a multidisciplinary team that values collaboration and team working. You will have the opportunity to develop both cutting-edge wet-lab skills working with animal and human PCLS as well as computational quantitative skills in developing predictive mathematical models and machine learning approaches.
Dr Laura Sidney (UoN), Dr Felicity de Cogan (UoN), Dr Anna Peacock (UoB) and Dr Darren Ting (UoN)
Ocular surface disease is a significant cause of blindness. Current treatments relying on repeat dosing of steroids show poor levels of patient compliance. Alternative treatments such as corneal or amniotic membrane transplantation require complex surgery. This gives a clear unmet clinical need to address in this project.
In this project the student will develop a novel cell therapy using mesenchymal stromal cells applied to the eye via a modified contact lens. The cells respond to the wounded environment to deliver signalling molecules that cause anti-inflammatory action and wound healing.
The project will cover 4 main objectives: 1) Working with industrial partners to generate and characterise a contact lens functionalised with synthetic peptides to allow cell attachment; 2) Assessing the effect of the functionalised contact lens on the metabolism and phenotypes of stem cells in tissue culture; 3) Building an ex vivo inflammation model of the ocular surface; 4) Assessing the efficacy of the functionalised contact lens in the ex vivo model. It is a wet-lab project incorporating methodologies from chemistry, materials science, molecular biology, human tissue handling and high-throughput protein assays and will provide the student with training in many different translational skills.
Prof Thomas Yates (UoL), Dr Francesco Zaccardi (UoL) and Dr Alex Rowlands (UoL) with Dr Richard Russell and Dr Kishan Bakrania Reinsurance Group of America
How we lead our lives effects our health, yet this information is typically not considered when predicting future risk of chronic disease or mortality. For example, an individual with a high genetic risk of a disease or a high risk based on routine clinical data is placed in the same high risk pool regardless of how physically active they are, despite the fact that physical activity can modify much of this risk for some long-term conditions and mortality outcomes. The studentship will include training in cutting edge analytical approaches for using data gathered from wrist worn accelerometers (similar to those found in smart watches and physical activity trackers) in generating patterns of physical behaviours, ranging from sleep to physical activity. The relevance of these novel metrics to predicting the onset of common chronic disease or early mortality will then be explored using flexible parametric models, which will include developing new risk prediction tools.
Dr Robert Owen (UoN), Dr Alexandra Lordachescu (UOB), Prof Felicity Rose (UoN) and Prof Ricky Wildman (UoN)
New approaches to bone repair are essential to meet the clinical need for tissue substitutes in many pathologies. This project aims to create a new type of bone graft that harnesses the ability to control cell behaviour through their physical environment. It is known that cells respond to cues (e.g. shape) in their environment, however this is not yet translated therapeutically due to many technical limitations. With novel advancements and the opening of the University of Nottingham’s new Additive Biofabrication Laboratory within the Biodiscovery Institute, we can now employ state-of-the-art 3D printing technology to address this complex question. The project combines unique biomanufacturing and analytical capabilities both at Nottingham and in the University of Birmingham’s School of Chemical Engineering’s Healthcare Technologies Institute.
Working with experts in 3D biomanufacture and mammalian cell/in vitro tissue culture, this interdisciplinary project will allow you to work at the interface of engineering and biology disciplines. You will have the opportunity to develop skills in high-resolution 3D printing, engineering tissue analogues, biochemical assays, and advanced imaging techniques. With these skills, you will discover how we can tune materials to promote bone formation and manufacture these into a new type of medical device.
Dr Maria Dauvermann (UoB), Prof Rachel Upthegrove (UoB) and Dr Mohammad Zia Ul Haq Katshu (UoN)
In this project, we will develop a new model using structural equation modelling to examine interrelationships between different factors that may contribute to depressive symptoms in individuals with early psychosis or psychotic experiences, including cytokine levels, structural brain measures and cognitive deficits. We will test and replicate this model in three existing large datasets. The student will engage with interdisciplinary researchers of a psychologist, cognitive neuroscientist, psychiatrists and a radiologist. The student will gain computational skills (Matlab and R), coding their own scripts and analysis structural brain scans.
Prof Jason Parsons (UoB), Prof Colin Watts (UoB), Dr Victoria Wykes (UoB) and Professor Stuart Green (UHB)
Glioblastoma (GBM) is the most common brain cancer in adults, but where survival rates remain extremely poor largely due to the inherent resistance of the tumour to therapies, including radiotherapy. However, the emergence of precision targeted proton beam therapy (PBT) and boron neutron capture therapy (BNCT) offer alternative modes of radiotherapy that can significantly reduce the side effects observed with conventional X-ray radiotherapy, whilst also being more effective in tumour cell killing. Despite this, there are still biological and clinical uncertainties with PBT and BNCT, requiring research in appropriate preclinical GBM models to derive the optimal radiotherapy strategy that can be used in the clinical for the benefit of GBM patients.
This exciting DTP studentship will develop novel radiation biology research investigating the impact of PBT and BNCT, versus X-rays, in overcoming the radioresistance of GBM. This will be delivered through the unique radiotherapy facilities available in Birmingham, in combination with GBM cell lines, 3D spheroids/patient-derived organoids and a chick embryo tumour model. This research is at the interface of translational and clinical medicine, and along with the expertise of the team in radiation biology, physics, and oncology, has high probability for improving outcome of GBM patients with radiotherapy.
Dr Alba Llibre (UoB), Prof Claudio Mauro (UoB) and Prof Andrea Cooper (UoL)
Tuberculosis is a major public health problem and new treatments are urgently needed. New drug-discovery approaches focus on changing the way our immune system reacts to
infection, helping it to fight back.
During an infection, our immune cells engage on glycolysis to rapidly produce energy to mount an efficient response. This results in lactate formation, first considered a waste product, now recognised as a modulator of immune responses, a concept we seeded in the research community. The way in which lactate exerts this effect is not known.
This project will 1) investigate the mechanisms behind lactate-mediated driven immune functions, trying to understand exactly how lactate impacts immune function and infection outcome. We will use state-of-the-art techniques, including high resolution microscopy at the single cell level, and immune cells from human lung, a rare and precious resource; 2) assess the therapeutic potential of targeting lactate to treat tuberculosis. The candidate will infect human/mouse lungs with Mycobacterium tuberculosis ex vivo and mice in vivo, manipulate cell responses to lactate through specific inhibitors, and determine infection resolution.
This project represents a unique opportunity to ease the pathway towards novel treatments for an ancient disease, using cutting-edge science in an excellent, supportive research environment.
Dr Clare Davies (UoB), Prof Eva Petermann (UoB), and Prof Abeer Shaaban (UHB)
The arginine methyltransferase PRMT1 is upregulated in breast cancer and is a major drug target for pharmaceutical companies. Despite this, it is still poorly understood how PRMT1 promotes cancer, particularly in context to DNA replication.
Using quantitative proteomics, we have identified a novel PRMT1 substrate, that is a chromatin-interacting protein. Whilst this protein is also upregulated in breast cancer and is known to regulate gene expression, our data now suggests that is also plays a role in DNA replication. The mechanism by which this occurs is completely unknown, nor is it understood if PRMT1 inhibitors synergises with drugs that target replication fork stability and G2 checkpoint, or if cells that are dependent on methylation of our novel protein are more sensitive.
Using a range of molecular and cell biology approaches, this project will address these important questions. These include DNA fibre analysis, replication and damage associated foci, checkpoint signalling and proteomics. Translational potential will be assessed using in vitro proliferation assays and mouse models of breast cancer. Together, this project could reveal new approaches in which PRMT1 inhibitors can be used in combination with replication stress-inducing agents or checkpoint inhibitors for breast cancer therapy.
Dr Rahul Mahida (UoB), Dr Amanda Tatler (UoN), Dr Aaron Scott (UoB) and Dr Dhruv Parekh (UoB)
Progressive Pulmonary Fibrosis (PPF) is a devastating condition which causes worsening breathlessness and disability, with a high mortality rate. Macrophage metabolic reprogramming and dysfunction are implicated in PPF pathogenesis, however the mechanisms remain unclear. The aim of this studentship will be to determine the role of extracellular vesicles in mediating macrophage dysfunction and reprogramming in PPF. The objectives will be to characterise the function and metabolic profile macrophages from PPF patients, determine the biological effect of extracellular vesicles on macrophages in vitro and using ex-vivo human lung slice models of fibrosis, and determine whether these effects can be reversed. This is an exciting and highly topical project, which could identify new therapeutic targets for PPF. A range of translational research skills will be taught, including flow cytometry, fluorescence microscopy, qPCR, Luminex, Seahorse metabolic profiling, macrophage functional assays, electron microscopy, mass spectrometry proteomics, microRNA profiling, digital spatial transcriptomics, and Western blotting. This project benefits from access to human lung tissue from surgical resections; the student will learn how to isolate primary macrophages from tissue and use precision-cut lung slices in models of pulmonary fibrosis. The student will work collaboratively with an integrated team of discovery scientists and translational clinical academics.
Prof Dorothee Auer (UoN), Prof Richard Bowtell (UoN), Dr Peter Harvey (UoN) and Dr Martin Wilson (UoB)
Glioblastoma is the deadliest brain cancer with poor survival rates despite improved understanding of its genetic causes; novel treatments in lymphomas offer survival benefits for some people with lymphomas, but when treatments fail, the median survival time is ~5 months. One reason for these poor treatment responses is the complex way in which cancer cells adapt their energy production, through a process called metabolic reprogramming. A lot of current research is therefore focused on producing a better understanding of metabolic reprogramming, so as to inform the development of effective treatments.
MRI is usually based on signals from hydrogen in water and fat, but it is also possible to make images based on signals from deuterium. As there is only a very small amount of naturally occurring deuterium in our bodies, after feeding someone with a compound containing deuterium the signal we detect mainly comes from ingested material. Measuring deuterium signals following ingestion of labelled glucose allows us to track metabolic processes involved in energy production in brain tissues. We have implemented this deuterium metabolic imaging (DMI) approach on our 7T scanner, and this PhD project will focus on applying DMI to understanding metabolic reprogramming in aggressive glioblastoma and lymphoma tumours.
Prof Ian Sayers (UoN), Dr Robert Hall (UoN), Prof Louise Wain (UoL) and Dr Nick Shrine (UoL)
We have made significant advances in identifying genetic variants that increase the risk of lung function impairment and chronic obstructive pulmonary disease (COPD), including recently 26 genetic variants that are potentially deleterious to protein structure/function.
The aim of this PhD studentship is to focus to these potential deleterious coding variants/genes and use a combination of genetic epidemiology, molecular biology, primary cell/tissue models to provide insight into disease mechanisms and identify potential therapeutic opportunities.
We will investigate predictive models for the impact of variants on protein structure. Candidate genes will be prioritised for functional work based on predicted protein alterations, single cell and spatial gene and protein expression profiling and scope for targeting by drugs. We will prioritise a subset of candidates for functional evaluation in a series of in vitro models ranging in complexity including primary cell, multicellular, lung tissue models in combination with genome editing to understand the role of the proteins and variant proteins in cell homeostasis and initiate studies to target altered mechanisms.
This studentship is part of a collaboration involving the Universities of Nottingham, Leicester, and Cambridge and will include training and skills development in genetic epidemiology, bioinformatics, genome editing, molecular biology, cell biology and imaging.
Prof Simon Woodward (UoN), Dr Isolda Romero-Canelón (UoB) and Dr Huw Williams (UoN)
A 4-year PhD studentship is currently available in a Chemistry-Pharmacy-Bioscience team coordinated by Simon Woodward, Huw Williams and Isolda Romero-Canelón to be filled as soon as possible, for an October 2024 start.
The student will be based in both the Universities of Nottingham and Birmingham and involved in research leading to a multidisciplinary PhD involving the optimisation and understanding of a unique anti-pancreatic cancer pro-drug.
Recently, we have discovered a new and unusual titanium-based compound that shows dramatic activity against therapeutically highly challenging pancreatic cancer cell lines (link1, link2). Preliminary evidence suggests our compound achieves this by a complex cell signalling process. This MRC-backed PhD will untangle how this is achieved, giving the candidate exceptional skills in medicinal chemistry, cancer biology and ultra-high field multi-nuclear biological NMR in a new and exciting area.
Training will alternate between Birmingham and Nottingham leading to skills in practical chemistry and biology, advanced instrumentation and theory.
The successful candidate will come from a background in chemistry, pharmacy, bioscience or medicine and will be curious to explore new avenues in cancer biology and advance unusual agents towards their use in the clinic.
Dr Christian Jenul (UoL), Dr Katrin Schilcher (UoL) and Dr Freya Harrison (UoW)
This project seeks to understand how bacterial pathogens from polymicrobial infections interact with each other and how these interactions shape infection progress and outcome. We will use bacterial pathogens that frequently co-infect the lungs of people with a genetic condition called cystic fibrosis (CF). These bacterial pathogens secrete metabolites into the infection environment, which allow them to compete or cooperate with other microbial organisms. We will use a unique porcine ex vivo lung model to re-create the CF lung environment and subsequently apply microscopy, mass spectrometry guided metabolite analysis and bacterial genetics to i) unravel how co-infecting bacterial pathogens influence each other’s behaviour, ii) how this influences the dynamics of the infection and iii) how these processes are stirred by secreted metabolites. The successful student will receive hands-on training in bacterial genetics, mass spectrometry and metabolite analysis and get the chance to work with an established ex vivo lung model. Understanding the dynamic processes that shape the interaction between bacterial pathogens will ultimately help the development of new treatment strategies for polymicrobial infections.
Prof Sue Jowett (UoB), Prof Guiqing Lily Yao (UoL), Dr Semira Manaseki-Holland (UoB) and Dr James Hall (UoB)
Severe floods are an increasing annual problem in parts of India and South Asia, worsened by global warming. Medical responses to floods traditionally have yet to include NCD services in India and many low and middle-income countries, and patients and health care professionals require need more structured plans. Our NIHR-funded project in Kerala aims to develop and evaluate a model of health service and community preparedness and response that would improve outcomes of NCD patients affected by floods.
A PhD studentship is available at the University of Birmingham for a PhD researcher based in Birmingham, UK to assist in conducting an exploratory and highly novel decision model-based health economic analysis to assess the longer-term cost-effectiveness of a complex-intervention to improve NCD care and outcomes in flooding events. The research will also involve relevant systematic reviews, and resource use and health outcome data collection. The UK health economics candidate will travel to India to gain context and collect data.
This project is a collaboration between the University of Birmingham, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum in Kerala, Indian Institute of Technology Roorkee, Mahavir Cancer Research Centre, and Doctors for You in Bihar.
Prof Sylwia Bujkiewicz (UoL), Prof Richard Riley (UoB) and Dr Sam Khan (UoL) with industry partner Dr Daniel Jackson (AstraZeneca)
When new cancer therapies are developed, they are evaluated in clinical trials assessing treatment’s impact on patients’ outcomes. Long-term survival is an outcome typically of interest to decision-makers, who recommend which new treatments should be available on NHS. However, modern cancer therapies are often targeted to small subsets of patients who harbour a particular biomarker. Therefore, data from clinical trials evaluating the effectiveness of therapies in a cancer subtype may be limited. Other sources of data; based on alternative outcomes, study types or other cancers, may need to be synthesised efficiently for reliable policy decisions. You will apply a range of modern tools from biostatistics (including Bayesian statistics, meta-analysis and survival analysis), epidemiology and data science and develop novel approaches for evaluation of cancer therapies.
This project is part of an exciting collaboration with University of Birmingham and AstraZeneca. You will benefit from an experienced supervisory team with expertise in statistics and oncology and an industry partner. This PhD in Biostatistics will provide you with an opportunity to develop advanced analytical skills, gain insight into drug development and decision-making processes and influence important decisions in healthcare. A suitable candidate will have MSc in Statistics, Medical Statistics or a related discipline.
Dr Anvesha Singh (UoL), Prof Csaba Sinka (UoL), Prof Susan Francis (UoN) and Prof Gerry McCann (UoL)
There is a global pandemic of type-2 diabetes. Diabetic cardiomyopathy is a well-recognised complication, which manifests with early alterations in left ventricular (LV) structure and function. Its pathophysiology and management remains poorly understood. This inter-disciplinary (Engineering, Cardiology, Physics) and cross-institution (Universities of Leicester and Nottingham) project aims to develop a state-of-the-art computational model of the heart in a healthy individual and those with diabetic cardiomyopathy. The starting point is a multi-physics based computational framework coupling the differential equations describing the constitutive behaviour of heart muscle, transmembrane potential, conductance and active stress leading to the contraction of the myocardium. Calibration of the constitutive model parameters will be carried out using cardiac magnetic resonance (CMR) imaging and electrocardiographic (ECG) data. The project will focus on the study of the nature of the active stress and its mechanical description as the current formulations are relatively simplistic. We will develop a direct coupling parameter which includes cardiac microstructure information for both healthy and diabetic patients. Development of an ex-vivo model of diabetic cardiomyopathy will increase our understanding of the pathophysiology of remodelling and allow testing of potential therapies.
Dr Hyojin Park (UoB), Dr Jack Rogers (UoB), Prof Rachel Upthegrove (UoB), Prof Matthew Broome (UoB), Dr Elizabeth Liddle (UoN) and Prof Peter Liddle (UoN)
This is an exciting opportunity to undertake a PhD in a cutting-edge collaborative project situated at the crossroads of the CHBH and IMH, University of Birmingham and Institute of Mental Health, University of Nottingham, in CHR individuals.
Our focus is on individuals at CHR for psychosis, where disorganised thoughts, evident in atypical speech processing and auditory hallucinations, represent fundamental symptoms that often precede the first episode of psychosis. This project will investigate the neural mechanisms governing the influence of speech rhythms and vocal emotions on both intelligible speech processing and emotional states within CHR individuals. Our goal is to pave the way for the development of efficient neurobiological markers capable of identifying those at risk of developing psychosis.
We will use state-of-the-art techniques, including OPM-MEG, DWI, and non-invasive rhythmic stimulation, in tandem with cutting-edge deep learning/machine learning algorithms based on Large Language Models. As a part of this project, you will gain invaluable experience in leading neuroimaging projects, mastering the aforementioned techniques. You will also actively participate in the recruitment process and conduct psychometric assessments. Furthermore, your statistical skill-set will flourish as you handle large datasets and receive training in advanced multivariate statistical analyses.
You will be supported by a diverse and accomplished supervisory team, comprising world-leading experts from the Centre for Human Brain Health and the Institute for Mental Health at UoB and UoN. Our interdisciplinary communities are open to individuals from diverse backgrounds, fostering an environment where collaboration thrives, and members are encouraged to forge new partnerships while contributing to the broader mission of our centres.
Dr Davinia Fernández-Espejo (UoB) and Dr Sang-Hoon Yeo (UoB)
Prolonged disorders of consciousness (DOC), caused by the most severe brain injuries, lead to catastrophic disability and complex care needs. While DOC patients are considered to be entirely unconscious, some are in fact conscious but simply unable to show it because they also have damage to the parts of their brain that control movement. Consequently, many patients survive for years ‘trapped’ in their unresponsive bodies. This project will use cutting-edge non-invasive brain stimulation and neuroimaging methods (including focused ultrasound stimulation -FUS- and magnetic resonance imaging -MRI-) to develop an intervention that can help repair these movement control brain networks. We will conduct a series of well-controlled studies in healthy volunteers first, before translating our methods to DOC patients themselves. By combining FUS with MRI, and using advanced analysis methods, we will characterize the effects of FUS over networks of interest and investigate whether specific characteristics of the brain anatomy or function can predict the degree to which an individual will respond to the stimulation. If successful, our intervention will have a profound impact on patients’ quality of life and level of recovery by allowing them to interact with their external world for the first time since their injury.
Prof Mark Humphries (UoN) and Dr JeYoung Yung (UoN) and Dr Jonathan O’Keefe from industrial partner Machine Medicine Technologies Ltd (London)
Parkinson’s disease has debilitating motor symptoms of tremor in the limbs, slowness of movement, and freezing, unable to move. A highly effective treatment is electrical stimulation deep in the motor regions of the midbrain. But surgery for this deep brain stimulation is only offered to around 2% of all patients, and about a quarter of those who receive it have poor outcomes. Optimising the selection of patients for deep brain stimulation will widen access to treatment, improve treatment outcomes, and prevent harm. The goal of this project is to test how fusing clinical data, neuroimaging, and video assessments could optimise the selection of patients. The project will be in collaboration with MachineMedicine (London), a MedTech company specialising in Parkinson’s disease, and the movement disorders clinical team at St George’s Hospital, London. The goal of the collaboration is to build an app used in-clinic for patient selection. MachineMedicine are leading the app development, building on their existing app for capturing movement video in-clinic. The clinical team at St George’s are running a trial of Parkinson’s patients to acquire the essential clinical data on patient symptoms, neuroimaging (including fMRI of spontaneous brain activity), and video capture of movements. In joining this collaboration, the PhD student will be trained in data-science and machine learning tools, including how to extract and analyse MRI and fMRI data, in fusing data across modalities, and in developing a machine-learning pipeline for predicting patient outcomes. These predictions will be tested against the 12-month follow-up data from the St George’s trial patients. The student’s further training will include a 3-month placement at MachineMedicine, and visits to St George’s clinic
Prof David Brook (UoN), Dr Aditi N Borkar (UoN), Dr Emma Hesketh (UoL) and Dr Christopher Parmenter (UoN)
We aim to uncover the molecular mechanisms underlying RNA misfolding diseases, particularly focusing on myotonic dystrophy (DM). In DM, both voluntary and involuntary muscles progressively degenerate in the body, affecting normal functioning of the eye, heart, endocrine system and central nervous system. DM is caused when repetitive CUG motifs in the DMPK mRNA fold abnormally and form RNA-protein condensates with the MBNL proteins in the nuclei of muscle cells. This process inhibits MBNL’s regular function in mRNA splicing and results in DM symptoms.
DM has been extensively studied over the past several decades. Yet, we don’t fully understand the molecular interactions between the disease state DMPK mRNA and MBNL proteins that lead to the observed pathophysiology. To address this gap in knowledge, we will employ a multidisciplinary approach involving cell biology, various microscopy techniques, and structural biology methods to directly study native DMPK mRNA-MBNL interactions in the disease state and in the presence of small molecule inhibitors.
This research holds profound implications for millions of people facing life-altering symptoms due to RNA misfolding diseases. By shedding light on their molecular intricacies, the project will contribute to collaborative publications of global significance, novel drug development, clinical applications, and intellectual property advancements.
Dr James Turner (UoB), Prof Leigh Breen (UoB), Prof Iskandar Idris (UoN) and Dr Oluwaseun Anyiam (UoN)
This project will establish whether adipose tissue inflammation and immune system deterioration exacerbates declining skeletal muscle mass and function with ageing and obesity. This topic is important, because populations worldwide are ageing, and the number of people worldwide who are obese is increasing. In this project, by recruiting younger and older overweight and obese people, we will examine whether inflammatory molecules in serum, or secretions from immune cells and adipose tissue, influence skeletal muscle properties in-vitro. In addition, we will examine how bariatric surgery changes the properties of adipose tissue, and we will design a randomised-controlled-trial that tests whether exercise combined with a low-calorie diet, counters adipose tissue inflammation and improves skeletal muscle properties invitro and in-vivo. The successful candidate will work within a cutting-edge research environment, with exposure to clinical procedures in the NHS, helping to develop a range of skills important for a scientific career, such as research design, participant recruitment, assessing diet and body composition, and working with blood and adipose tissue samples. Advanced laboratory skills will be developed, including cell culture, western blotting, and flow cytometry. Supervisors will provide expert training in data analysis, writing for publication, and disseminating findings to a variety of audiences.
Prof Tania Dottorini (UoN), Dr Michelle Baker (UoN), Prof Julie Morrissey (UoL), Dr Stephen Heeb (UoN) and Prof Hany Elsheikha (UoN)
Antimicrobial resistance (AMR) poses a major global health threat. Among respiratory infections, Staphylococcus aureus and Pseudomonas aeruginosa caused around 360,000 and 139,000 deaths, respectively, due to antibiotic resistance. Unfortunately, there is a stark lack of new drugs in the pipeline to treat these resistant infections, making it imperative to research new targets. In this project, we will develop an artificial intelligence (AI) approach to discover potentially new S. aureus and P. aeruginosa druggable proteins and to identify lead drugs inhibiting the target by a deep learning approach fed with 3D modelling. Taking large genomic data sets we will use cutting edge AI approaches to identify genes linked to antibiotic resistance. We will then experimentally validate these using CRISPR/Cas9 and transcriptomics technologies. Finally for confirmed drugs targets we will identify and experimentally test, drug compounds that could be developed into new treatments for AMR infections. This project based within an international research group, is at the frontier of AMR research taking a multi-disciplinary approach to explore a full pipeline from bacterial sequence to drug discovery.
Dr Christopher O’Shea (UoB), Prof Andre Ng (UoL), Prof Claudio Mauro (UoB), Dr Davor Pavlovic (UoB) and Dr Katja Gehmlich (UoB)
Chronic kidney disease (CKD) is a major and growing health concern. By 2040 it is likely to be the 5th biggest killer worldwide. CKD often results in cardiac dysfunction, and it is cardiac complications that most commonly lead to mortality in CKD patients. What is unique about CKD-induced cardiac disease, and therefore how best to treat it, is not fully understood. Current research focuses on end stage CKD, but by then it is often too late to reverse any cardiac disease. In this studentship, we will model early CKD, how this detrimentally effects the heart, and whether we can treat CKD-associated cardiac disease. CKD causes systemic inflammation, and we believe this plays a key role. We will therefore fully profile the inflammatory state of early CKD. We will then use cutting-edge techniques to study the structure of the heart, and map electrical behaviour across the entire organ. We will then translate our findings towards the clinic using more human models, and human cardiac cells differentiated from induced pluripotent stem cells. This research will offer insights into inflammation’s role in early CKD-associated cardiac disease and provide evidence for novel preventive treatments for patients.
Prof Willem van Schaik (UoB) and Dr Andrew Millard (UoL)
The human gut harbours a complex microbial ecosystem, termed the ‘gut microbiome’ that is stable in healthy individuals. However, in critically ill patients, the gut microbiome is often highly dynamic and is characterised by an overgrowth of opportunistic, antibiotic-resistant pathogens, like Escherichia coli and Enterococcus, which can cause difficult-to-treat infections. In this project we will characterise whether bacteriophages (viruses that infect bacteria) against these opportunistic pathogens are present in the gut microbiome of patients and whether the bacteriophages can infect and kill these bacteria in a model gut microbiome system. We will also determine whether there is a risk that bacteriophages can integrate microbial DNA in their own genomes and then transfer this to other strains of the same species, as this could potentially contribute to the rapid dissemination of important biological traits, including antibiotic resistance and virulence. With this project you will develop skills in microbiology, including in phage biology, and in DNA-sequencing based methodologies (metagenomics and bioinformatics). The data generated in the project may be used for the development of novel phage-based therapies to prevent and treat overgrowth of the gut by opportunistic pathogens.
Dr Sovan Sarkar (UoB), Prof Timothy Barrett (UoB) and Prof Daniel Tennant (UoB)
Nervous system disorders include common diseases like dementia, and rare genetic disorders, often childhood-onset. However, finding cure for ~150 rare diseases is challenging because of their rarity, low commercial incentive, and limited knowledge of disease process. We aim to establish shared disease mechanism for developing a common therapy to improve the health of children with rare, early-onset forms of neurodegeneration like Niemann-Pick type C1 (NPC1) disease and Wolfram syndrome (WS).
Autophagy, a cellular homeostatic process essential for cell survival and human health, is commonly deregulated in neurodegenerative diseases including NPC1 and WS. We showed that loss of autophagy reduces cell viability via depletion of a metabolite called nicotinamide adenine dinucleotide (NAD), which mediates mitochondrial depolarisation and cell death.
In this project, we will utilize disease-affected cortical neurons generated from patient-derived induced pluripotent stem cells (iPSCs) to establish defective autophagy-NAD axis as a shared patho-mechanism in two rare diseases. We will then determine the best combination of FDA-approved autophagy-inducing drugs and NAD precursors used as nutritional supplements for achieving greater therapeutic efficacy and demonstrating generalisability.
The project will involve iPSC culture, neuronal differentiation, metabolomics, high-content imaging, drug testing, and cell biology and biochemical studies for autophagy, mitochondrial function, and cell death.
Dr Gabriela da Silva Xavier (UoB), Dr Nick Hannan (UoN), Dr Ildem Akerman (UoB) and Prof Tarek Hiwot (UHB)
Want to make a difference? Want to engage with cutting edge research and gain skills that will be highly sought after?
This PhD project will suit a candidate who is driven to search for a cure for a rare disease called Alström syndrome for which there is currently no disease modifying treatment. As a PhD student you will extend our preliminary work on human pancreatic beta-cells (the cells that make insulin), which indicate that beta-cell dysfunction is a primary defect in Alström syndrome and could lead to many of the complications observed in patients living with Alström syndrome.
You will generate a human embryonic cell line using CRISPR-CAS9 technology to model Alström syndrome. You will apply a cell differentiation protocol, to generate pancreatic beta-cells. You will use these beta-cells to dissect the mechanisms through which Alström syndrome affects function, using a combination of biochemical and cell biology techniques, cutting edge microscopy, and next generation sequencing to assess cell function and differentiation status. You will then assess the efficacy of small molecules to correct dysfunction. All of this whilst working with experts in the techniques you will be using, based at the Universities of Birmingham and Nottingham.
Interested? Please email firstname.lastname@example.org
Sophie Joanisse (UoN), Prof Kostas Tsintzas (UoN), Dr Amy Naylor (UoB) and Prof Simon jones (UoB)
Osteoarthritis (OA) is a degenerative joint disorder affecting synovial joints, its occurrence increases with age and, it is more common in women. Worryingly, OA is accompanied by a peri-articular loss of muscle mass which can further exacerbate the inevitable age-associated loss of muscle mass. This loss of muscle can precipitate frailty leading to increased risk of falls and fractures in addition to increasing the risk of developing co-morbidities. The overall aim of the studentship is to determine the underlying causes of muscle loss of people with OA. We hypothesize that factors released by the affected bone (e.g., local environment) will drive muscle loss observed in OA.
This PhD studentship will provide interdisciplinary training in a wide range of cell techniques including human primary (bone and muscle) cell isolations (OA/controls) and culture, the use of novel in vitro models (self-structuring bone model (SSBM)/osteoblast mechanical stress) and the establishment of novel co-culture models (SSBM and myoblasts/myotubes) to study bone-muscle crosstalk. The student will also be trained in a variety of molecular biology techniques. In addition, the student will spend time at both the Universities of Nottingham and Birmingham to gain essential skills and further establish their interdisciplinary network.
Prof Derek Irvine (UoN), Prof Don Sharkey (UoN) and Prof Alexander Morgan (UoN) with Jonathan Waggott from industrial partner Angel Guard Limited
Hospital Acquired Infections (HAI) are a leading cause of death and/or severe long-term illness in premature babies. Preterm infants acquire HAI’s during prolonged residence in intensive care units (ICU), often transferred from medical equipment such as their incubator or water-based aerosols from washing/cleaning. This project will develop new sustainable materials of construction for ICU equipment, that will both resist microbial colonisation (reducing infections and improving outcomes) and reduce the healthcare sectors dependence on petrochemicals (reducing carbon-footprint).
This is a multidisciplinary project lead by Nottingham’s Centre for Additive Manufacturing (Engineering), comprising ~100 researchers hosted in state-of-the-art facilities. The team also includes a neonatologist (School of Medicine), a biomaterials scientist (Faculty of Science) and our industrial collaborator (Angel Guard Ltd).
The student will develop the new materials and test them in-use, working closely with Angel Guard. There will be opportunities to train at the Harwell Research Complex learning cutting edge analytical skills and spend time at research-active neonatal ICU to better understand the clinical needs. This PhD will suit a highly ambitious chemistry/engineering graduate, wishing to undertake a truly translational clinical/industry linked project. The student will be well placed to secure follow-on funding for clinical trials or on-going development/commercialisation.
Dr Michelle Buckner (UoB), Dr Michael Cox (UoB), Dr Fiona Whelan (UoN) and Prof Alice Turner (UoB)
Antimicrobial resistance (AMR) causes significant morbidity and mortality. The key driver of AMR is the use and misuse of antimicrobials. The human conditions responsible for the highest levels of antibiotic prescriptions is chronic obstructive pulmonary disease (COPD). COPD is a chronic inflammatory disease which results in difficulties breathing. Importantly, a disordered lung microbiome has been implicated in worsening symptoms of COPD. Surprisingly though, little is known about the levels of AMR that reside within the COPD lung microbiome. We hypothesise that the frequent use of antibiotics in this patient population will drive the evolution of antibiotic resistance and select for the transmission of AMR genes between lung microbiome members. This project will use a unique combination of whole genome sequencing, culturomics, and phenotypic analysis to investigate a pre-existing collection of COPD microbiome isolates to determine the levels of AMR within these bacteria and their potential to be transmitted between strains.
We provide an interdisciplinary supervisory team of bioinformaticians and microbiologists, scientists and clinicians. This project provides an excellent opportunity for the student to build on their existing skills in microbiology and to develop skills in highly sought after areas, including AMR, genomics, respiratory disease, microbiome science, statistical analysis and bioinformatics.
Prof Steve Bull (UoL), Dr James Hodgkinson (UoL) and Prof Martin Dyer (UoL) with Dr Lurdes Duarte from industrial partner Isogenica
The startling statistic that 1 in 2 people are predicted to develop some form of cancer during their lifetime means there is an urgent need to develop new cancer therapeutics. However many cancer drugs adversely affect healthy cells which can cause serious side effects in patients that prevent these drugs from progressing into the clinic. To overcome this, this studentship will target the preparation and evaluation of novel antibody-drug conjugates (ADCs) for the targeted delivery of inhibitors of key MCL1 proteins that are critical for malignant B-cell proliferation in leukaemia. MCL1 is an important cancer drug target, however clinical trials with current MCL1 inhibitors have been halted due to safety issues. Antibody mediated delivery of these MCL1 inhibitors to malignant B-cells using ADCs could harness the high therapeutic potential of these MCL1 inhibitors, whilst removing potential safety concerns. In this studentship you will be involved in a highly interdisciplinary chemical biology project, involving the chemical synthesis of novel MCL1 antibody-drug conjugates to treat B-cell malignancies that cause leukaemia. This studentship will provide you with many of the chemical biology skills required to pursue a career in the life sciences in academia/biotech or carry out drug discovery in the pharmaceutical industry.
Dr Robert Mahen (UoL), Dr Gianmarco Contino (UoB) and Prof Andrew Fry (UoL)
Centrosomes are microtubule-based organelles with important functions in diverse cellular processes. They are critical for cell division, cell migration and cell shape changes – all of which are important to the development of cancer. Centrosomal abnormalities have long been recognised in cancerous tissue, and evidence is growing that they directly drive carcinogenesis. However, how centrosomes become defective in tumor tissue, and how this might contribute to the development of specific types of cancer is still mysterious.
In this project we will tackle this mystery by using cutting edge forms of microscopy and genomics to understand how centrosomes assemble and function, both in healthy and cancerous cells. We will investigate how abnormal centrosomes contribute to the development of a lethal form of cancer – oesophageal adenocarcinoma. Overall, this project is an exciting opportunity to receive interdisciplinary training in different types of advanced imaging, genomics and cellular models of cancer, and you will have the opportunity to work in different labs at both the University of Leicester and the University of Birmingham.
Dr James Hodgkinson (UoL), Prof John Schwabe (M), and Dr Emma Hesketh (UoL) with Alex Brown, Duncan Smith and Valerie Pye for industrial partner Sygnature Discovery (Peak Proteins)
This PhD project is an exciting opportunity to explore the innovative drug strategy involving proteolysis targeting chimeras (PROTACs) using Cryo-Electron microscopy, a cutting-edge structural biology technique, at the University of Leicester. The project is in collaboration with a world-leading drug discovery CRO. PROTACs are novel bi-functional drugs that promise to ‘drug the undruggable’ by marking target proteins for degradation rather than inhibition. The proteins SOS1, a guanine nucleotide exchange factor, and LSD1, a lysine histone demethylase, are important cancer therapeutic targets with substantial prospects for future drug development.
SOS1 plays an essential role in the KRAS signalling pathway. Inhibitors of SOS1 have shown considerable potential for targeting RAS-driven tumours. LSD1 plays a critical role in the endothelial to mesenchymal transition that is a key step in allowing tumours to metastasize. Inhibition of LSD1 has been shown to be a promising treatment for melanoma. To determine the structure-activity relationship of these PROTACS, you will use state of the art cryo-electron microscopy at the regional facility based at Leicester, and chemically synthesise novel PROTACs for evaluation using cryo-electron microscopy. In partnership with the drug discovery CRO you will learn interdisciplinary techniques in medicinal chemistry, protein expression/purification and structural biology amongst industry experts.
Dr Christopher Switzer (UoL) and Prof Melanie Madhani (UoB)
Embark on an exhilarating journey at the forefront of cardiovascular research by joining this cutting-edge PhD program in collaboration with the University of Birmingham, specifically focused on the dynamic interplay of Reactive Sulfur Species (RSS) in the aftermath of acute myocardial infarction (AMI). AMI, a global health concern, triggers a cascade of events, including inflammatory responses that impact cardiac function. Led by world-renowned experts Prof Madhani and Dr Switzer, our research explores the enigmatic role of RSS in this critical scenario. Prof Madhani’s discovery of RSS in oxygen-deprived cardiac cells sets the stage, while Dr Switzer’s revelations of the dual nature of RSS, possessing both cyto-protective and pro-inflammatory attributes, add an intriguing dimension to whether RSS can influence the inflammatory response after AMI. Cutting-edge techniques, such as live cell imaging and mass spectrometry, will unveil the impact of RSS on inflammatory signalling and gene expression in cardiac cells. The anticipated outcomes of this ground-breaking research will not only enrich our understanding of RSS but also pave the way for transformative strategies to mitigate tissue damage in myocardial infarction patients. You will contribute to unravelling the secrets of an unexplored realm in redox biology, making a lasting impact on cardiovascular science.