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Characterisation of novel human disease proteins involved in chromosomal instability.

Project Description

Genome instability is a fundamental feature of cancer and can arise via many different pathological mechanisms. Deciphering how individual gene variants, especially those identified by whole exome sequencing, contribute to the disease phenotype and/or response to therapy is extremely challenging, particularly if the function of the gene is unknown and/or there are no relevant knockout animal models available. However, the study of rare human genome instability disorders provides a unique, naturally occurring model with which to study the pathological impact of single gene mutations on both development and cancer susceptibility.

Over the past few years our laboratory has characterised a number of novel genes with roles in DNA replication and/or genome instability (Mol. Cell 2018, 71, 25-41; Nature Genetics 2017, 49, 537-49 and 2016’ 48, 36-43; Mol. Cell 2015, 59, 462-77). We have identified a number of other candidate DNA repair genes whose mutation is likely to have fundamental effects on genome stability. It is the aim of this studentship to characterise one of these in detail.

During the course of this project, the student will use a range of laboratory-based, experimental techniques to assess the integrity of the cellular DNA damage response and mitotic progression, including Western blotting, immunofluorescence, immunoprecipitation, mass spectrometry, single molecule DNA fibre analysis, siRNA/DNA transfection, in vitro cell culture and a variety of widely used molecular biology techniques.

The deadline for applications is 4th October 2019. Successful applicants will have experience in laboratory research, and will be highly motivated and ambitious. They will have a collegiate mind set, and as well as benefitting from the diverse expertise, resources and opportunities the Centre studentship programme has to offer, they will be willing to work in partnership with Centre colleagues to promote and publicise the research of the Centre. As part of this, the studentship will provide opportunities for science engagement activities in the cancer area.

Person Specification
Applicants should have a first or upper second class BSc or Masters degree in a relevant subject, preferably within the field of DNA damage, repair and replication. Previous laboratory experience is essential. Applicants should have a strong commitment to research, strong interpersonal skills, and a willingness to take part in public engagement activities.

How to apply
Informal enquiries should be directed to Grant Stewart ()

Applications should be directed to David Piela ()

To apply, please send:
• A detailed CV, including your nationality and country of birth;
• Names and addresses of two referees, ideally who have supervised your laboratory research, but excluding proposed supervisors for the project;
• A personal statement highlighting your research experience/capabilities and your reason for applying for a PhD studentship at the CRUK Birmingham Centre;
• Copies of your degree certificates with transcripts;
• Evidence of your proficiency in the English language, if applicable.

Funding Notes

Funded by an ITN (Initial Training Network) Marie Sklodowska-Curie grant. Successful applicants will be university employees with an annual salary.

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