PhD studentship in Northern Institute for Cancer Research: Investigation of the effects of DNA repair inhibitors in pre-clinical models of neuroblastomas with ATM, MYCN and TP53 abnormalities

Number of awards:

1

Start date and duration:

October 2017 for 3 years.

Application closing date:

31 July 2017. Interviews week beginning 14 August 2017.

Overview:

Cancer is associated with increased expression of oncogenes and loss of tumour suppressor genes. Many proteins in the DNA damage response (DDR), are tumour suppressors, e.g. TP53. The DDR is a complex network of DNA repair and cell cycle checkpoint proteins and defects in the DDR are common in cancer.

High risk neuroblastoma (NB) is one of the most difficult childhood cancers to cure. Around 50% of high risk NB have amplification of the MYCN oncogene which promotes DNA replication and hence cell proliferation, but also causes replication stress. Loss of ATM, a key component of DDR, which signals to cell cycle checkpoints and DNA repair and loss of TP53 function are also common in NB. These aberrations are potentially exploitable by targeting complementary aspects of the DDR. Targeting the DDR is an exciting new development in cancer therapy with PARP inhibitors, including rucaparib that was developed in Newcastle, now licenced for certain cancer types associated with specific DDR defects. ATR inhibitors are a promising new development that are in early clinical trials. The replication stress caused by MYCN amplification causes sensitivity to ATR inhibition and loss of ATM confers sensitivity to PARP and ATR inhibitors in other cell types.

The first aim of this research is to determine if NB cells harbouring MYCN amplification and/or ATM or other DDR defects are more sensitive to ATR and PARP inhibitors as single agents and in combination with conventional therapy. The second aim is to develop predictive biomarkers to identify those patients most likely to respond to ATR and PARP inhibition.

Sponsor:

Children’s Cancer and Leukaemia Group, Little Princess Trust

Name of supervisor(s):

Professor D Tweddle (http://www.ncl.ac.uk/gnch/staff/profile/deborah.tweddle) and Professor N Curtin, Northern Institute for Cancer Research (http://www.ncl.ac.uk/cisban/people/profile/nicola.curtin)

Eligibility Criteria:

You must have, or expect to achieve, at least a 2:1 Honours degree in biology, biochemistry, biomedicine, or a related area. A further qualification such as an MSc or MRes is advantageous.

This award is available to UK/EU applicants. If English is not your first language, you must have IELTS 7 with at least 6.5 in the written component, or equivalent.

How to apply:

You must apply through the University’s online postgraduate application system. To do this please ‘Create a new account’ (http://www.ncl.ac.uk/postgraduate/apply/).

Only mandatory fields need to be completed. However, you will need to include the following information:

insert the programme code 8300F* in the programme of study section
select ‘PhD in the Faculty of Medical Sciences – Cancer Research’ as the programme of study
insert the studentship code CR081 in the studentship/partnership reference field
attach a covering letter and CV. The covering letter must state the title of the studentship, quote the studentship reference code CR078 and state how your interests and experience relate to the project
attach degree transcripts and certificates and, if English is not your first language, a copy of your English language qualifications

*The online application system will only allow one application using the programme code 8300F. If you are applying for TWO or more projects using that code then you will need to email our Postgraduate Admissions Service ([Email Address Removed]) with the following information:

your applicant number (from the first project application that you submitted online)
the second studentship code and its corresponding title
a two page covering letter for the second project

Our Postgraduate Admissions Service will then forward this information to the relevant selector in the Faculty of Medical Sciences.