Regenerating the genetic predisposition to medulloblastoma using human neuroepithelial stem cells

Medulloblastoma is the most common malignant brain tumour in children. Four distinct clinical groups of this tumour, with very different response to treatment and ultimate outcome (molecular subgroups) have been identified through large-scale sequencing studies.
Approximately one-third of patients have tumours with activation in the sonic hedgehog (SHH) pathway. Mutations in the SHH-receptor Patched (PTCH) are found in 25% of this sub-type and some patient also have activation of the N-MYC oncogene. There are essentially no new advances in brain tumour treatment that have increased survival for children with medulloblastoma in the last decade. In this project, we will genetically manipulate medulloblastoma precursor cells to produce medulloblastoma in culture and in vivo, and we will use novel small-molecule MYCN- and SHH-pathway inhibiting drugs to develop new treatments for this deadly disease.

The student will learn to use cutting-edge techniques in culture of stem- and progenitor-cells, and in CRISPR/CAS9 and other gene-editing technologies to induce precise genetic changes into these cells. The project will provide unique exposure to translational cancer drug development working with novel small-molecule discovery platforms in place at ICR, one of the largest centres for drug-development in the world. ICR and The Royal Marsden Hospital have delivered approximately 20 next generation cancer drugs to clinical trials in the last two decades, and the campus provides rich exposure to all relevant techniques that are utilised in modern cancer drug development, including in vitro and in vivo drug validation, cancer modeling, pre-clinical testing and medicinal chemistry.

The project will uncover mechanisms and therapeutic approaches useful to combat this fatal brain tumour in children and will provide a unique opportunity to acquire advanced techniques in therapeutic drug screens, target identification, and drug development, all core strengths of the ICR.

The Chesler laboratory is a pioneer in modeling and targeting of children’s solid tumours, and in clinical sequencing of paediatric malignancy, and has developed several precision-targeted cancer drugs now in first-in-child clinical trials for children with difficult-to-treat cancers.

Download a PDF of the complete project proposal: https://d1ijoxngr27nfi.cloudfront.net/docs/default-source/studying-at-the-icr/11_chesler_tailor_chopra_cruk-brain-tumour-studentship.pdf?sfvrsn=61eb5e69_2

Candidate profile
Candidates must have a first class or upper second class honours BSc Honours in biochemistry, neuroscience, stem cell biology, genetics or cancer biology

How to apply
Full details about these studentship projects, and the online application form, are available on our website, at: www.icr.ac.uk/phds Applications for all projects should be made online. Please ensure that you read and follow the application instructions very carefully.

Closing date: Monday 19th November 2018
Applicants should be available for interview 28h and 29th January 2019.

Please apply via the ICR vacancies web portal
https://apply.icr.ac.uk/