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Graduate Studentships

 

 

MRC Cancer Unit - PhD Opportunities, 2020

The Medical Research Council Cancer Unit at the University of Cambridge is a leading centre for cancer research in the UK.  Our aim is to undertake research that advances our understanding of the earliest steps in the emergence of cancer, and to use this knowledge for early diagnosis, risk stratification and clinical intervention, through the development of innovative enabling technologies.  The Unit is based within the Hutchison/MRC Research Centre on the Cambridge Biomedical Campus, and possesses excellent research facilities, strong collaborations with clinicians and colleagues in other disciplines, and a vibrant and supportive working environment.

We have the following PhD projects on offer for entry in October 2020, with funding available through studentships from the Medical Research Council.  Eligibility and Funding criteria apply and are stated below.

 

Clonal dynamics of a metastatic benign cancer – Dr Ben Hall

Dermal cylindroma is a rare inherited disease of multiple benign, disfiguring tumors caused by inherited mutations in the gene CYLD.  These typically grow on the head and neck, causing extreme discomfort to patients.  The tumours that develop are highly heterogeneous and have distinct columnar structures.  Surprisingly, benign metastases have been reported suggesting that cylindroma may offer insights into the interaction of the tumour and the environment associated with metastasis in cancer more generally.

In this studentship the patterns of mutation observed in two key (DNMT3A and BCOR) taken from biopsies will be analysed to model the growth and development of cylindroma.  The student will build models of clonal growth and competition in the disease using data shared by clinical collaborators in the Nik-Zainal group.  Over the course of the PhD the student will identify the underlying hierarchy of cells, before investigating the role of different genes in the development and progression of the disease.

More information about the research undertaken in the Hall Group can be found here: https://www.mrc-cu.cam.ac.uk/research/benjamin-hall-folder

 

Oncogene-induced reprogramming of heterotypic cellular interactions

 Dr Alessandro Esposito and Dr Jacqueline Shields

The accumulation of mutations during the development of cancer subverts normal cell-to-cell communication and cellular decisions.  Deciphering the mechanisms that underlie cell decisions such as fate determination, cell cycle regulation and cellular migration is critical not only to identifying the molecular determinants of disease but also to the development of future cancer therapies.  In particular, our understanding of the role and mechanisms of heterotypic cellular interactions during oncogenesis and therapy is severely lacking, hampered by methodological challenges associated with monitoring cell-to-cell communication between individual cells over time.

Dr Alessandro Esposito and his team have established techniques to enable live imaging of biochemical activities with subcellular resolution, light-inducible control of enzymatic activities, tracking and modelling of cellular populations.  We are applying these unique tools to the study of how oncogenic KRAS mutations alter cell signalling and metabolism, and cellular phenotypes during early oncogenesis.  Dr Jacqueline Shields and her team investigate how the “normal cells” of the tumour microenvironment - the stroma - regulate immune activity from early stages of disease to promote carcinogenesis.  To do this, we examine both the primary tumour and draining lymph nodes developing complex culture systems and organ-on-a-chip models to monitor heterotypic cell interactions with low invasiveness.

This project will exploit these novel technologies to understand how oncogenic KRAS mutations alter cell-to-cell interactions between wild-type and mutant cells or between mutant cells and stroma contributing to the deregulation of tissue homeostasis during early oncogenesis.  The project will offer a unique opportunity to train across disciplines through a strong partnership between groups specializing in oncology, engineering and biophysics.

More information about the research undertaken in the Esposito and Shields groups can be found here: https://quantitative-biology.org

 www.mrc-cu.cam.ac.uk/research/Jacqui-Shields-folder

 

Uncovering the (epi)Genomic regulation of cancer forming processes using integrative computational genomics and deep learning approaches

– Dr Shamith Samarajiwa

Mutations in oncogenes and tumour suppressor genes, copy number changes and other genetic aberrations, together with anomalous epigenomic modifications all conspire to alter gene expression programmes, perturb normal cellular processes and promote tumour formation.  Perturbation of signaling pathways and networks, transcription factor binding patterns, reconfiguration of the three dimensional chromatin architecture, and changes in regulatory element activity and interactions enable tumour formation and cancer progression.  Understanding these processes will enable development of therapies as well as development of cancer early detection applications.

This project will use integrative computational approaches and large biomedical data-sets to develop and apply computational biology and machine learning (including novel deep learning solutions) methods to understand the complex systems involved in cancer formation and progression.

This project will bring together big data analytical, modelling, data-mining and visualisation approaches.

Novel integrative methods will be developed and applied to multi-omic cancer datasets.

Unique data integration approaches will be applied including modelling biological systems as knowledge graphs.

Cutting edge computational biology and genomics approaches will be combined with deep learning methods (Convolutional neural networks (CNNs), generative methods such as variational autoencoders (VAEs) and generative adversarial networks (GANs) together with other machine learning methods.

 

 

Requirements:

A masters degree in a quantitative field (data science, machine learning, deep learning, computational biology, mathematics, statistics or engineering) is required.  Candidates with Biomedical or Medical degrees with exceptional (R and/or Python) programming and analytical skills with a good understanding of cancer biology, immunology or metabolism are also welcome to apply.

More information about the research undertaken in the Samarajiwa group can be found here: https://www.mrc-cu.cam.ac.uk/research/Shamith-Samarajiwa-folder

Samarajiwa lab: https://www.samarajiwa-lab.org

 

Early detection of clinically-relevant mutational signatures

– Dr Serena Nik-Zainal

Mutational signatures in human cancers are the final outcome of combinations of DNA damage and DNA repair processes.  Direct DNA damage incurred by tobacco smoke, UV light or other environmental mutagens and direct abnormalities of a DNA repair pathway like homologous recombination (HR) repair or mismatch repair (MMR) leave characteristic imprints on the genome.  However, abnormal cellular processes like replication stress can result in mutagenesis as well, albeit indirectly.  Mutational signatures are therefore simply a read-out of a spectrum of cellular abnormalities and can thus be thought of and exploited in that way.  In this studentship, which shall be a combined wet-lab/dry-lab project, we aim to identify on-going mutational signatures that can be used as a surrogate for particular cancer development processes and determine signatures that may be informative for therapeutic intervention.  Apart from identifying clinically relevant mutational signatures, we aim to design mutational-signature-based clinical assays that could be used for early detection.  We will test our assays, optimize their performance and demonstrate how well they perform in a clinical screening setting.

More information about the research undertaken in the Nik-Zainal group can be found here: https://www.mrc-cu.cam.ac.uk/research/serenanikzainal

 

Eligibility and Funding

We welcome applications from those holding or expecting to obtain at least an upper second class degree (or equivalent) in a relevant scientific subject.  These studentships are funded by the Medical Research Council and are open to UK and EU applicants only.  Other international students are not eligible to apply.  UK applicants will be eligible to receive full funding of University and College fees and a stipend of £18,000 p.a.  EU applicants will be funded on a fees-only basis, unless they meet the MRC's eligibility criteria for residency (visit the MRC website for further details: www.mrc.ac.uk/skills-careers/studentships/studentship-guidance/student-eligibility-requirements/).  Successful applicants will be registered with the University of Cambridge.

How to apply

All applications will need to be made through the University Application Portal and will entail an application fee of £65.  Please visit: www.graduate.study.cam.ac.uk/courses/directory/cvcupdmsc/apply for further information about the programme and to access the Applicant Portal.  Please note that the course code for PhD applications to the MRC Cancer Unit is MDCU22.  Whilst making your online application please make it clear which project area(s) and principal investigator(s) you are interested in working with.  Your online application will need to include:

 

  • A CV, including full details of all University course grades to date.
  • Contact details for two academic or professional referees.
  • A personal statement outlining your interest in a specific project area, what you hope to achieve from a PhD, and your research experience to date.

 

The above information must be provided under relevant sections on the application portal.

Completing the Research section

If you are applying for one project only:  in the ‘Proposed title of Research’ textbox, insert the project title.  If you wish to apply for more than one project, insert ‘Cancer Research’.

If you are applying to more than one supervisor:  in the ‘Proposed Supervisor’ textbox, please insert the initials of the Supervisors you wish to consider your application and in the ‘Research Summary’ textbox, please insert the project titles being offered by those Supervisors.

Please describe your research experience in the appropriate textbox.

The closing date for applications is 15th November 2019, with interviews expected to take place in December.

Please contact studentships@mrc-cu.cam.ac.uk with any other enquiries concerning studentships or eligibility criteria.