Funding and Finance

MRC Case MRes/PhD Studentship - Exploiting the ATR-CHK-1 Axis for Selective Cancer Therapy

  • Northern Institute for Cancer Research
  • Reference Code: NCR97


Closing Date: 26th March 2010

Details:

Lead supervisor: Professor Nicola Curtin
Institute: Northern Institute for Cancer Research
Sponsor: MRC Industrial CASE
Duration: 4 years (MRes Medical and Molecular Biosciences followed by a three-year PhD)

A bright and energetic student is sought to undertake studies within the DNA damage response group at the Northern Institute of Cancer Research.

The ATM and Rad3-related (ATR) and cell cycle checkpoint (CHK-1) kinases are key components of the DNA damage response (DDR). They signal DNA double strand breaks to S-phase and G2/M phase cell cycle checkpoints and to DNA repair by homologous recombination (HR). 

Many anti-cancer drugs act by inducing DNA double strand breaks and the effects of these agents is enhanced if ATR/Chk1 is not activated. Importantly, sensitisation is specific to replicating cells, in particular those defective in the G1 checkpoint. Loss of the G1 control is a characteristic of cancer, due to mutations in tumour suppressors, such as p53 and Rb, up-regulation of the G1 cyclins and CDKs and down-regulation of their inhibitors. Disruption of ATR/CK1 signalling should therefore be selective to cancer cells.

This PhD will investigate the effects of CHK1 and ATR modulation for chemo- and radio-sensitisation in genetically-defined cell lines, using molecular genetic and small molecule chemical biology approaches. Proof-of-mechanism (POM) and proof-of-concept (POC) pharmacodynamic biomarkers will be identified. Ultimately the research may lead to the identification and validation of new targets/drugs for cancer treatment.

The project will involve molecular and cell biology techniques including human cell culture and cytotoxicity assays, RNA-knockdown, flow cytometry and cell synchronisation, DNA damage and repair and cellular kinase assays by immunological and immunofluorescent microscopy

This project will start in September 2010.

Person Specification
You should have, or expect to achieve, a first-class or upper-second-class Honours degree, or MSc in a relevant subject.

Value of the Award and Eligibility
Depending on how you meet the MRC’s eligibility criteria, you may receive a full award (covers fees and an annual stipend of £13,290) or a partial award (covers fees only).

How to Apply
You must complete the University’s postgraduate application form, quoting the reference number NCR97, and attaching a copy of your CV and covering letter. Select “Master of Research/Doctor of Philosophy (Medical Sciences) – Cancer Research” as the programme of study.

Closing date for applications: 26th March 2010

Further Information
For more details, please contact Professor Nicola Curtin, n.j.curtin@ncl.ac.uk