Peter Bailey (Respiratory medicine)
Anne Ramsay Bowden (Clinical genetics)
Supervisors for OOPE: Professor Steve Jackson and Dr Julian Sale
Supervisor for PhD: TBC
Elizabeth Goode (Gastroenterology)
Supervisor: Dr Carl Anderson
Emily Lees (Immunology)
Supervisor: Professor Gordon Dougan (TBC)
Ludovica Marando (Haematology)
Supervisor: Dr Brian Huntly (TBC)
Norman Shreeve (Obstetrics and gynaecology)
Supervisor: Dr Francesco Colucci
Ondrej Suchanek (Immunology)
Supervisor: Dr Menna Clatworthy TBC)
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Nirupa Desai (Haematology)
Supervisor: Prof Venki Ramakrishnan (LMB) â ACF
Clare Burdett (Cardiothoracic surgery)
Supervisor: Ruth Cameron & Serena Best (Materials Science & Metallurgy) â ACF
Limy Wong (Renal medicine)
Supervisor: Prof Ken Smith (CIMR)
Dan Greaves (Infectious disease)
Supervisor: Prof Paul Lehner (CIMR) â ACF, CMT
Harveer Dev (Surgical oncology)
Supervisor: Vincent Gnanapragasm (Hutchison/MRC) [Starting 2016] â ACF
Nicola Thompson (Medical oncology)
Supervisor: Prof David Adams (Sanger) â ACF
Grace Collord (Paediatric haematology)
Supervisor: Prof George Vassiliou (Sanger)
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Sarah Aitken (Histopathology)
âInvestigating the interplay between CTCF haploinsufficiency and DNA stability using genomic and proteomic approachesâ
Supervisor:Dr Duncan Odom (CRUK) â ACF
Ciaran Hill (Neurosurgery)
âTraumatic axonal injury and the role of neuroinflammation in progressive neurodegenerationâ
Supervisor: Prof David Menon (Anaesthesia) â ST
Imran Noorani (Neurosurgery)
âGenome-wide screening for co-operative driver genes and chemotherapeutic resistance genes of glioblastoma using transposon and CRISPR-cas9 mediated mutagenesis.â
Supervisor: Prof Allan Bradley (Sanger) â AFY
Johannes Reinhold (Cardiology)
âMitochondrial regulation of inflammation in atherosclerosisâ
Supervisor: Prof Martin Bennett (Cardiovascular Medicine) â ACF
Stephen Sammut (Oncology)
âThe circulating genomic landscape of early stage breast cancer.â
Supervisor: Prof Carlos Caldas (CRUK) â ACF
Kirsten Scott (Neurology)
âThe role of B lymphocytes in the development of Parkinsonâs disease and its associated dementiaâ
Supervisor: Prof Roger Barker (Brain Repair) â ACF
Michelle Toleman (Medical Microbiology)
âA comparison of standard infection control practice, whole-genome sequencing and infection tracking software to optimise the detection of Methicillin Resistant Staphylococcus aureus transmission in health care facilitiesâ
Supervisor: Prof Sharon Peacock (Medicine)/Prof Julian Parkhill (Sanger)
Faisal Basheer (Haematology)
âThe role of EZH2 in the induction and maintenance of acute myeloid leukaemiaâ
Supervisor: Brian Huntly (CIMR) â ACF
Ranna El Khairi (Paediatric Endocrinology)
âUse of human pluripotent stem cells to model monogenic diabetesâ
Supervisor: Ludovic Vallier (Sanger)
Saad Idris (Haematology)
âThe role of the B cell receptor and downstream signalling pathways in Non Hodgkins Lymphomaâ
Supervisor: Klaus Okkenhaug (Babraham)/Paul Kellam (Sanger) â ACF
Wajid Jawaid (Paediatric Surgery)
âResolving early mesodermal fate decisions at the single cell level to identify differentiation pathways and novel regulatorsâ
Supervisor: Prof Bertie Gottgens (Haematology)
Simon Johnston (Medical Oncology)
âBiological characterisation of FoxA1 regulatory factorsâ
Supervisor: Jason Carroll (CRUK)/Ultan McDermott (Sanger) â ACF
Oliver Mytton (Public Health)
âEnvironmental approaches to walking and cycling: interventions, mechanisms and health benefitsâ
Supervisor: David Ogilvie (MRC Epi Unit) â ACF
Mabel Teng (Medical Oncology)
âThe genetic landscape of circulating tumour cells and disseminated tumour cells in breast cancerâ
Supervisor: Peter Campbell/Thierry Voet (Sanger) â ACF
Zaeem Cader (Gastroenterology)
âCharacterizing the role of GPR35 in inflammatory bowel diseaseâ
Supervisor: Arthur Kaser (Dept of Medicine/Sanger)
Cristina Dias (Clinical Genetics)
âUnravelling the BAFopathies: high throughput molecular phenotyping of models of BAF complex mutations associated with intellectual disabilityâ
Supervisor: Darren Logan (Sanger)
Wendy Jones (Clinical Genetics)
âFrom monogenic to oligogenic: expanding the search for inheritance models in intellectual disabilityâ
Supervisor: Jeff Barrett (Sanger)
Thomas McKerrell (Haematology)
âThe prevalence and significance of clonal selection in healthy haematopoietic stem cells and its relationship to myeloid leukaemogenesisâ
Supervisor: George Vassiliou (Sanger)
Marko Nikolic (Respiratory Medicine)
âDevelopmental studies of murine and human lung development towards differentiation of human induced pluripotent stem cells to lung epithelial progenitorsâ
Supervisor: Emma Rawlins (Gurdon)
Rameen Shakur (Cardiology)
âElucidating the development of ventricular tachyarrhythmias in familial hypertrophic cardiomyopathiesâ
Supervisor: Derek Stemple (Sanger)
Tom Turmezei (Radiology)
â3D modelling of the hip joint from clinical imaging dataâ
Supervisor: Graham Treece (Engineering)/Ken Poole (Dept of Medicine)
PhD extension to March 2016
Constantine Alifrangis (Medical Oncology)
âEvaluation of combinatorial drug strategies to combat de novo and acquired drug resistance to targeted molecular therapyâ
Supervisor: Ultan McDermott (Sanger)
Neil Barrett (Paediatric Oncology)
âA study of the developmental biology of MLL-AF4 associated infantile leukaemia in a mouse modelâ
Supervisor: Katrin Ottersbach (CIMR)
Sam Behjati (Paediatrics)
âGenomic profile of radiation-induced cancerâ
Supervisor: Mike Stratton (Sanger) WTSI funded
Marc-Philip Hitz (Cardiovascular)
âGenetic determinants in left ventricular outflow tract obstructionâ
Supervisor: Matthew Hurles (Sanger)
Clara Podmore (nee Kelliny) (Metabolism)
âIron metabolism and its association with type 2 diabetesâ
Supervisor: Claudia Langenberg (MRC Epidemiology Unit)
Extension to PhD for maternity leave
James (Jimmy) Peters (Rheumatology)
âRegulation of gene expression in immune cell subsets in health and diseaseâ
Supervisor: Ken Smith (CIMR) MPhil in 1st Yr (4 yr funding)
Lucy Yates (Clinical Oncology)
âCharacterisation of the evolving genomic landscape in cancer relapse and metastasisâ
Supervisor: Peter Campbell (Sanger) WTSI funded
Supervisor: Steve Jackson
Functional characterization of responses to DNA damage in human cells
Failure of accurate DNA damage sensing and repairing mechanisms manifest as a variety of human diseases including cancer. Cytotoxic chemotherapy and radiotherapy remain the most beneficial in terms of cancer treatments and largely act through the generation of DNA damage. Research in Professor Steve Jacksonâs lab focuses on cellular responses to DNA damage, in particular, DNA double strand breaks.
Accuracy and efficiency of DNA damage detection and repair requires the recruitment and subsequent post-translational modification of various proteins. Ubiquitylation and sumoylation are highly dynamic and reversible enzymatic processes that play crucial roles during the execution of DNA damage sensing and repair. Further characterization of the enzymes involved in these processes is required in order to fully understand how the DNA damage response (DDR) is regulated and has the potential to provide new therapeutic targets.
My project centres around the functional characterization of putative SUMO E3 ligases that to date, have not been linked to the DDR.
Supervisor: Peter Jones
Advisor: Glyn Lewis
Investigating early life immune and metabolic function and psychotic symptoms
I am a psychiatrist and epidemiologist interested in early life risk factors, neurodevelopment and later schizophrenia, together with common links in childhood between chronic adult diseases, physical and neuropsychiatric.
Schizophrenia is characterised by mental phenomena but is also known to be associated with immunological and metabolic abnormalities. It has been proposed that these may contribute to causation of the neuropsychiatric disorder, and that there may be causes in common with chronic physical illnesses without obvious psychiatric components such as obesity and cardiovascular disease. There is evidence people who experience psychotic symptoms (e.g. hallucinations or delusions) may be at higher risk of developing schizophrenia. Therefore, studies of psychotic symptoms may increase our understanding of the development of psychotic disorders, and help to elucidate aetiological mechanisms.
My project is based on a prospective birth cohort of over 5,000 individuals born in the Bristol area in the early 1990s (ALSPAC). I aim to explore the effects of early immune and metabolic dysfunction in relation to psychotic symptoms (PLIKS), and childhood neurocognitive development. In the future, I aim to investigate this association further by incorporating genetic information, as well as linking our data with ongoing studies of structural brain imaging in individuals with PLIKS.
Supervisors: Kay-Tee Khaw & Paul Foster
The epidemiology of glaucoma
Glaucoma is one of the leading causes of blindness worldwide, second only to cataract. However, unlike cataract, visual loss from glaucoma is irreversible. Uncorrectable loss of vision is associated with threats to independent living, safety and emotional well-being, resulting in increased dependence on social and community services. It has been estimated that if 10% of glaucoma sufferers received earlier treatment that arrested significant visual loss, the United Kingdom economy would benefit by ÂŁ555 million. Currently, intraocular pressure (IOP) is the only known modifiable risk factor for glaucoma, and all treatment modalities are aimed at reducing IOP. Identification of lifestyle factors associated with glaucoma may enable public health strategies as well as new treatments to help prevent this disabling condition. EPIC-Norfolk is an established population study which this project will form part of. Extensive lifestyle data from multiple time points are available and the last health check included a comprehensive ophthalmic examination. The primary goals of this project are to describe IOP, optic nerve measures and glaucoma in the EPIC-Norfolk cohort, and to determine nutritional, lifestyle and biological measures associated with the presence of glaucoma and associated physiological measures.
MSc in Computational Biology
I am spending the first year of the programme doing an MSc in machine learning at UCL, which is the first time the optional masters has been undertaken at an institution other than Cambridge. Both the Wellcome Trust and those stewarding the programme in Cambridge were extremely helpful in facilitating this, reflecting the open-minded, forward-looking and scientific emphasis of this programme. Machine learning largely concerns automatic inference from data and has applications in almost all data-rich fields. A few medically relevant ones are automatic diagnosis, robotic surgery, genomics, and the study of the brain, the last of which I am principally interested in and hope to pursue in the subsequent PhD.
I would recommend the programme at Cambridge to anyone primarily motivated by scientific curiosity and keen to bridge divides between different scientific disciplines as well as those separating the clinic and the lab.
Supervisor: Pentao Liu & Colin Watts
Investigating the functional role of induced pluripotent stem cell technology in Type 1 Neurofibromatosis and its Neuro Oncological Complications
Type 1 Neurofibromatosis is a multisystem genetic disorder with cutaneous, orthopaedic, neurological and oncological manifestations. Animal models of NF1 have provided crucial insights into the biology of the NF1 mutation however, the failure of knockout mice to develop tumour spectra similar to the human condition reflects the major limitation of first-generation knockout modelling strategies.
To date, no group has attempted to model the pathogenesis of this condition using iPS cell technology. I aim to produce an in vitro / vivo neural differentiation model of NF1 using patient specific iPS cells. This will facilitate investigation of neuroglial development, variable expressivity and oncogenic transformation in the disease state. This approach in studying cancer development in a human cell line of combining cellular reprogramming, gene targeting, forward genetics and in vivo tumorgenicity assessment is at the frontier of molecular oncology. Furthermore, accurate reproduction of the abnormal neurodevelopmental program in NF1 and subsequent oncogenic transformation would represent a âpromising cellular tool for future drug screening and personalized treatment
Supervisor: Doug Fearon
Defining the origin and fate of Fibroblast Activation Protein (FAP) expressing cellsÂ in health and disease
Fibroblast activation protein (FAP) is a cell surface glycoprotein, which marks a subset of stroma cells in all human adenocarcinomas. We have shown that ablation of the FAP expressing cells from stroma results in immune dependent acute hypoxic necrosis of the tumour.
We have also found FAP expressing cells in some normal tissues such as skeletalÂ muscle and the bone marrow where they have essential roles in maintaining muscleÂ mass and haematopoesis. Furthermore FAP+ cells are present in the developingÂ embryo, in healing wounds and at sites of inflammation. These observations raise theÂ possibility that FAP+ cells may form a lineage, with a fundamental role in regulatingÂ inflammation and tissue regeneration and maintenance.
The aim of my project is to determine whether the expression of FAP marks a cellularÂ lineage and therefore the cells at these different sites are developmentally linked. I willÂ use a genetic fate mapping approach where FAP+ cells will be irreversibly marked in vivo at various stages of development and their fate then determined. Gaining a betterÂ understanding of these cells will have implications for modulating inflammation and tissue regeneration or repair.
Supervisor: Gordon Dougan, Ken Smith and Rob Kingsley
Hypervariable loci in a clonal pathogen: Characterisation of a two-component regulatory system in Salmonella enterica
Salmonella Typhi is the causative agent of typhoid fever, a bloodstream infection, which infects 27 million people a year worldwide and results in more than 200,000 deaths per year. The bacteria have adapted and many are now resistant to common antibiotics making it harder to eradicate this disease. Previous studies identified hypervariable genes in S. Typhi that may be involved in recent adaptation. These include a locus encoding a putative two-component regulator family protein for which the function is currently not known. These regulatory systems operate by exploiting a signal-sensing domain on a histidine protein kinase that autophosphorylates and then transfer the phosphoryl group to a cognate response regulator that mediates the activity of gene expression, in response to particular environmental signals. This project will explore the role by which natural variants of these genes influence the biology of S. Typhi, impacting on phenotypes such as virulence, metabolism and antibiotic resistance. The significance of this work is that through understanding how these genes operate we can develop new strategies to combat this ever-increasing threat to public health.
MPhil in Epidemiology
I qualified in medicine from the University of Edinburgh in 2003 and I went on to junior medical posts in Oxford. I am currently a Specialist Registrar in Geriatric Medicine. Older people as a whole represent a very heterogeneous population. As a geriatrician, I am interested in those that become frail. In frailty, multiple homoeostatic systems become less adaptable, especially in the face of physiological stress. This is particularly true of cognitive function in ageing. In the face of unprecedented demographic pressures, I’m attracted to the contribution of epidemiological methods to the study of ageing and dementia.
Longer term, I intend to stay on in Cambridge and undertake a PhD in cognitive epidemiology. I’ll continue having a small clinical commitment throughout my time in Cambridge and I eventually envisage a research career alongside a clinical appointment.
Supervisor: Mike Stratton
Exploring the cancer genomes of tumours derived from germline BRCA1 and BRCA2 mutations carriers
Cancers carry somatic mutations. Few are thought to be driver mutations that confer selective clonal growth advantage; the vast majority are passenger events that do not contribute to cancer development. The acquisition of complete catalogues of somatic mutations (drivers and passengers) from individual cancers by second generation sequencing techniques offers insight into the exogenous and endogenous factors that have influenced the cancer genome. Recently, massively parallel sequencing technology has been used to demonstrate how environmental factors like tobacco-smoke and ultra-violet exposure brands the cancer genome with characteristic mutational patterns.
Breast cancer is common with an incidence of 1 in 9 in the UK population. Germline mutations in BRCA1 and BRCA2 confer a significantly increased lifetime risk of breast and ovarian cancer over that of the general population.
Using second generation sequencing technology, a selection of tumours derived from germline BRCA1 and BRCA2 mutation carriers will be sequenced to explore the mutational load encumbered by germline defects of relevant DNA repair pathways. This will be compared and contrasted to the mutational burden of other common breast tumours. Mutational patterns will be sought; signatures characterised and factors such as surrounding sequence context and genomic architecture will be considered. This will hopefully yield insights into the mutational processes – DNA damage, repair processing, mutation and selection – in the evolution of these tumours.
Supervisor: Bill Harris
The role of microcephaly-associated genes encoding centrosomal proteins in neurogenesis and growth of the developing brain
Primary microcephaly (MCPH) is an autosomal recessive congenital disorder characterised by significantly reduced brain size (>3 SD below the age- and sex-related mean) occurring by 32 weeks gestation, along with mental retardation. The condition is genetically heterogeneous with 7 known loci and mutations identified in five human genes. Interestingly, four of these: ASPM, CDK5RAP2, CENPJ and STIL, encode centrosomal proteins whilst MCPH1 encodes a protein involved in DNA-damage repair that also associates with centrosomes during part of the cell cycle. In addition, mutations in PCNT, encoding another centrosomal protein, Pericentrin, have recently been identified as a cause of both Seckel syndrome and Majewski Osteodysplastic Primordial Dwarfism (MOPD II), conditions characterised by severe congenital microcephaly and reduced body size.
These conditions illustrate the importance of the centrosome and its associated proteins in human brain growth and development. The reduction in brain size in these diseases is thought to be due to reduced production of neural progenitors during neurogenesis. However, the specific roles of the associated genes during neural proliferation and the cellular effects of the mutations are not known.
My project aims to investigate the cell-biological basis of abnormal neurogenesis and reduced brain size caused by mutations in these genes, using the Zebrafish retina as a model system due to its accessibility and amenability to genetic manipulation and live imaging. I will examine the effects of altering the activity of these genes on cell proliferation and neurogenesis, via both morpholino knockdown and expression of mutant variants.
As mutations in ASPM are the most common cause of primary microcephaly in humans I am investigating this protein in particular detail via a collaborative project with Professor David Glover in the Department of Genetics. I will be using Drosophila embryos and human cell lines to identify the interactors of Drosophila Asp and human ASPM and to analyse the functional domains of these proteins. We hope that these studies may lead us to new potential candidate microcephaly genes which we could go on to study in our Zebrafish retina model system.
Supervisor: Allan Bradley
Natural and modified variations in human induced pluripotent stem cells
Human induced pluripotent stem cells (hiPSCs) have revolutionized stem cell biology. By genetic manipulation, fibroblasts have been shown to re-program to a pluripotent state similar to human embryonic stem cells. This would allow for patient specific hiPSCs, generating models for disease as well as immune compatible cell therapies. However, there are still many problems hampering both hiPSC derivation and differentiation. The knowledge gained from these genetic and cellular mechanisms would optimize strategies towards clinically relevant therapies.
Chong Yew Tan
Supervisor: Antonio Vidal-Puig
Role of fatty acid chain length on energy balance and adaptive thermogenesis
The overall theme of our research is to investigate the relationship between obesity and metabolic complications. Our aim is to understand the role of lipotoxicity and how this can be reversed either through a modification of lipid metabolism or an increase in lipid oxidation.
In infant humans and small mammals, brown adipose tissue (BAT) functions as a tissue for thermoregulation. This is achieved through its ability to uncouple oxidative metabolism; thus converting caloric energy, especially fats, into heat. BAT is present in both lean and obese adults and the possibility of activating BAT as a means of increasing caloric loss in obese states becomes an attractive option.
When BAT is activated, there is a simultaneous increase in both fatty acid oxidation and synthesis. In addition, the newly synthesized fatty acids are extensively modified, including acyl-chain elongation and desaturation. Our hypothesis is that the ability of BAT to modify fatty acids is crucial to its function. Specifically, fatty acid chain length and saturation helps determine its intracellular fate; either towards oxidation, storage or other cellular compartments. The aim of my project is to investigate the role of fatty acid composition on brown adipose tissue (BAT) metabolism and asses the impact of this alteration on whole body energy balance and thermoregulation.
Supervisor: Magdalena Zernicka-Goetz
Chromosome abnormalities and cell fate in pre-implantation development
Chromosome abnormalities in early development are responsible for a widerange of reproductive health problems including subfertility, miscarriage and the birth of an abnormal child. Up to 50% of human pre-implantation embryos created during IVF contain cells with chromosome abnormalities in a mosaic distribution, however a significant proportion of these embryos can undergo normal pre-implantation development. There is some evidence to suggest that in some cases these embryos may be able to self-correct, or regulate their development such that the pregnancy can continue without complication. Possible mechanisms for regulation include sequestration of abnormal cells to the extra-embryonic lineages, and apoptosis of the aneuploid cells within the inner cell mass population, thus depleting the abnormal cells from the future fetal lineage. The project objectives are to develop models of embryonic chromosome mosaicism and to develop and in-vivo chromosome marker and to use these tools to investigate aneuploid cell fate in early embryo development.