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MRC WIMM PRIZE STUDENTSHIPS 2023 The new admissions cycle for entry in 2023 is now open.

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Antanaviciute Group - Computational biology and machine learning for characterising spatial tissue niches and cellular signalling across space and time of human immune system development

Our research group interests lie at the intersection of computational biology and human immunology, in particular in the applications of ‘omics, single cell and spatial technologies for the better understanding of tissue microenvironment, local tissue dynamics and cellular interactions, how they are established during development, and the molecular perturbations and tissue remodelling that occurs in disease states, in particular in autoimmune and autoinflammatory conditions. In order to address these types of questions, our group focuses on inter-disciplinary expertise in both biology and computational biology to both to extract relevant biological insights from complex datasets and to develop domain-tailored machine learning models and novel computational methods for high-dimensional sequencing data analysis.

Bannard Group - Development and Maturation of Antibody-dependent Immune Responses

We study the cellular interactions and molecular events that lead to the development of high affinity and protective antibodies during humoral immune responses. Our main focus is the germinal centre reaction.

Chapman Group - Genome Diversification in Cancer and Adaptive Immunity

Research in the Chapman laboratory aims to better understand the biological pathways that allow for genome diversification as a physiological process, and those that lead to GI in cancer. We also work towards devising strategies to exploit the GI-driving pathways as vulnerabilities to selectively kill cancer cells.

Chakraverty Group - Design of advanced haematopoietic stem cell and T cell therapies

This is an exciting opportunity for a highly motivated graduates to join a new DPhil research programme in Oxford, the NIHR-funded Blood & Transplant Research Unit (BTRU) in Precision Cellular Therapeutics.

Davis Group - Therapeutic opportunities emerging from studies of immune checkpoints

Our focus has been on the cell biology of the T-cell surface. We developed general methods for crystallizing glycoproteins and determined the structures of key T-cell surface proteins including the first adhesion protein (CD2) and its ligand CD58, the costimulatory receptor CD28 and its ligand CD80, the large tyrosine phosphatase CD45, and most recently a ligand-bound T-cell receptor (TCR). We also worked out how weak, specific recognition is achieved by these types of proteins and obtained the first insights into the overall composition of the T-cell surface. Most importantly we proposed, with PA van der Merwe, one of the most complete and best-supported explanations for leukocyte receptor triggering, called the kinetic-segregation model (youtube.com/watch?v=HygSTSlycok).

de Bruijn Group: Developmental Haematopoiesis

Our aim is to obtain a mechanistic insight into the birth of hematopoietic stem and progenitor cells in embryonic development and determine the contribution of these cells to the emerging hematopoietic and immune systems of the embryo.

Dong Group - Human T Cell responses against viruses and cancer

Identification of key determinants affecting the quality of human cancer specific cytotoxic T cells

Drakesmith Group - Iron and Immunity

We study how iron and anaemia influence immunity and infectious diseases. Our research inspires therapies that control iron physiology to improve immunity, combat infections and treat disorders of iron metabolism. We work across the disciplines of immunology, haematology and global health, utilising in vitro, in vivo and human studies, and collaborate extensively to translate our mechanistic discoveries into clinically relevant progress.

Goriely Group - Clinical Genetics

De novo mutations (DNMs) are a significant contributor to human disease, affecting ~1:300 new births. We study the mechanisms by which these spontaneous mutations arise in the first instance, concentrating on the tissue where most originate, the human testis. We aim to understand why some pathogenic mutations arise more frequently than others and how the mechanisms regulating the production of sperm influences this process.

Higgs Group - Laboratory of Gene Regulation

Our laboratory is interested in the general question of how mammalian genes are switched on and off during lineage commitment and differentiation. We use the most recent genomics technologies and computational approaches to study both the entire genome and individual genes in detail. We study all aspects of gene expression including the key cis-regulatory elements (enhancers, promoters and insulators), the transcription factors and co-factors that bind them, the epigenetic modifications of chromatin and DNA, and the role of associated phenomena such as chromosome conformation and nuclear sub-compartmentalisation using state-of-the-art imaging techniques. These studies are performed both in cell systems and in model organisms as well as in material from human patients with various inherited and acquired, genetic and epigenetic abnormalities. The translational goal of our work is to develop new ways to modify gene expression during blood formation with the aim of manipulating gene expression and ameliorating the clinical phenotypes of patients with a variety of blood disorders.

Koohy Group - Applications of multi-omics and AI to better understand T cell immunity and antigen-specificity

An effective T cell response is orchestrated upon T cell recognition of MHC-presented antigens on the surface of infected cells or specialized antigen-presenting cells. A deeper understanding of the rules underpinning T cells recognition of antigens would allow further harnessing of the adaptive T cell immunity and may lead to the development of new personalized vaccines and other immunotherapeutic strategies. The research interests in the Koohy’s group are focused on development of machine-learning and statistical model to help us better understand the grammar of adaptive T cell immunity. Here are a few examples showcasing a few active research projects:

Mead Group - Haematopoietic Stem Cell Biology

The overarching focus of my research group is to characterise genetic and cellular heterogeneity in myeloproliferative neoplasms (MPN) with the ultimate goal to improve the diagnosis, risk-stratification and treatment of these largely incurable forms of blood cancer.

MRC Enterprise Studentship - Imaging-based analysis of signaling pathways triggered by immune checkpoint receptors

LEAD SUPERVISOR: PROFESSOR SIMON J. DAVIS, RADCLIFFE DEPARTMENT OF MEDICINE Co-supervisor: Dr Oliver Bannard, Nuffield Department of Clinical Medicine Commercial partner: MiroBio Ltd / Gilead Sciences, Oxford

Nerlov Group - Single Cell Biology of Hematopoietic Stem- and Progenitor Cells in Blood Cancer and Ageing

The Nerlov laboratory studies the fundamental processes by which blood stem cells sustain blood cell production throughout life, and how ageing and haematological malignancies perturb this process.

Patel Group - Origins of Genotoxic metabolism and the DNA damage response in stem and cancer cells

Our work has shown that metabolism both generalized and intrinsic to blood stem cells unleashes reactive metabolites such as the aldehydes – formaldehyde and acetaldehyde. Such metabolites damage DNA causing the stem cells to die or to accumulate cancer causing mutations. Fortunately, a two-tier protection mechanism ensures that these aldehydes do not irreversibly damage these stem cells.

Rehwinkel Group - Nucleic Acid Sensing During Virus Infection

Virus infection is a constant threat to the cells of all living organisms. To counter this threat, cellular receptors detect virus presence and activate potent antiviral immune responses. Some of these sensors of virus presence signal for the activation of innate immune genes, which in humans include type I interferons. These cytokines then alert neighbouring, uninfected cells and induce the expression of hundreds of genes, many of which encode proteins with direct antiviral function. Viruses in turn have developed strategies to counteract and evade detection and control by the innate immune system. As such, cells and viruses are in a dynamic arms race in which host defence mechanisms and viral counter-measures rapidly co-evolve. Our aim is to investigate the molecular mechanisms by which mammalian cells recognise and respond to infection by viruses.

Twigg/Wilkie Group - Building the skull – normal and abnormal development

Using a combination of patient samples and mouse models, we study the causes and developmental origins of skull malformation. The work ranges from screening human DNA for new mutations, to use of genome editing and single cell transcriptomics to model the developmental causes of these malformations in mice. Projects on offer would particularly appeal to students interested in genetics, genomics and developmental mechanisms and for whom clinical application is a key motivator. There will be particular opportunities to learn core bioinformatics skills, perform single cell analysis, and use genome editing to generate and characterise mouse models to understand disease mechanisms.

Wilkinson Group - From basic biology to novel translational applications of haematopoietic stem cells

The Wilkinson group focuses on the biology and translational applications of blood-forming haematopoietic stem cells (HSCs). In cancer evolution and its therapy, HSCs may play the part of the villain or the hero. As a long-lived stem cell population, HSCs gradually accumulate genetic mutations and are therefore thought to be a cell-of-origin for several haematological malignancies. This has recently been strikingly seen in the clinical observation of Clonal Haematopoiesis of Indeterminate Potential (CHIP), where the peripheral blood cells become increasingly derived from a single HSC clone. CHIP is considered a pre-malignant state because it increases the risk of myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML), and it is also a major risk factor for therapy-related myeloid malignancies. The genetics of this pre-malignant state are now well characterized, however, the cellular and molecular mechanisms are still incompletely understood.