PhD studentship - Characterising the biology of high-risk group 4 medulloblastoma to develop novel and risk-adapted therapies

Number of awards:

1

Start date and duration:

4 year PhD starting December 2018/January 2019.

Overview:

High-risk cancers are a major cause of death in childhood; there is an urgent need for innovative therapies which could lead to improved outcomes. Our research focuses on the most common central nervous system tumour of childhood, medulloblastoma. Although survival rates have improved, there remains groups of patients for whom current multimodal treatments are ineffective. The largest molecular subgroup of medulloblastoma (MBGrp4; ~45% of patients), has recently been identified by us to harbour further discrete molecular subtypes; MBGrp4-LowRisk, defined by frequent characteristic cytogenetic aberrations and favourable survival outcomes and MBGrp4-HighRisk, with a paucity of recurrent cytogenetic aberrations and poor survival outcomes. This studentship will focus on the biological and functional characterisation of these subtypes, enabling the identification of novel treatment options and disease targets and will investigate the interplay between a hypothesised mutation-driven defective chromatin remodelling phenotype and sensitivity to chemo- and radiotherapeutic treatments.

We will first investigate the molecular pathology of MBGrp4 by integrative analysis of large scale -omics datasets derived from state-of-the-art technologies, including RNA-sequencing, DNA methylation profiling, and NGS mutational panels. Evidence of correlation between these data and associated clinico-pathological information will be sought to identify and validate biologically-relevant, clinically actionable targets. Patient derived xenograft (PDX) disease models will be established for the in vivo assessment of identified targets. Finally, these models will be used to investigate the mechanistic basis of MBGrp4 subtype response to current chemo- and radiotherapeutic regimens in terms of their differing chromatin remodelling phenotypes, or other, identified phenotypes/genotypes. The Northern Institute for Cancer Research (NICR) is the focus of research excellence in translational cancer research at Newcastle with an annual research income of ~£10m and >250 personnel, including over 60 post-graduate research students.

Sponsor:

Cancer Research UK

Name of supervisor(s):

Dr D Hicks, Northern Institute for Cancer Research (https://bit.ly/2CsskXo)
Dr E C Schwalbe, Northumbria University and Northern Institute for Cancer Research (https://www.northumbria.ac.uk/about-us/our-staff/s/edward-carl-schwalbe)
Professor S C Clifford, Northern Institute for Cancer Research (https://www.ncl.ac.uk/nicr/staff/profile/steveclifford.html#background)

Eligibility Criteria:

Candidates must have a BSc in an appropriate biological sciences discipline at first or 2:1 level, or a Masters degree in a relevant subject (e.g. cancer research).

How to apply

You must apply through the University’s online postgraduate application form (https://bit.ly/2Qwk2Rn). 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 CR087 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 CR087 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.

Contact:

For further details please contact Dr Debbie Hicks (https://bit.ly/2CsskXo) ([Email Address Removed]), Dr Ed Schwalbe ([Email Address Removed]) or Professor Steve Clifford ([Email Address Removed])