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PhD Studentship - 'Modelling the Cross-communication of Childhood Brain Tumours with Healthy Brain'

University of Nottingham - Medicine

Qualification Type: PhD
Location: Nottingham
Funding for: UK Students, EU Students
Funding amount: £15,009 per annum
Hours: Full Time
Placed On: 12th April 2021
Closes: 30th May 2021
Reference: MED1589

Location: UK Other

Project:

Atypical teratoid/rhabdoid tumours (AT/RT) are the most common malignant brain tumours in children under 6 months of age and account for 20% of cases in children 3 years old and younger. Median survival is approximately 1 year with no current standard treatment. The high frequency of AT/RT in patients younger than 3 years old complicates the use of radiotherapy following surgery. There is therefore an urgent need to develop more effective chemotherapy treatment regimens, predicated on a better understanding of underlying biology.

This 3-year PhD project funded by the Little Princess Trust, aims to model the interaction of AT/RT cells with healthy brain cells from the cerebellum, to better understand how signals from the tumour microenvironment promotes the survival and propagation of recurrent AT/RT post-surgery. A panel of patient-derived AT/RT cells will be co-cultured with fluorescently-tagged cerebellar astrocytes and decellularised human brain extracellular matrix (ECM). This will ensure that this 3D model (which we term ‘Tumoursphere Matrix’) is physiologically-accurate, where AT/RT cells receive signals from healthy astrocytes and brain-specific ligands from the ECM. 

Upon co-culture, fluorescence-activated cell sorting will be used to separate AT/RT and astrocyte cell populations, which genome-wide gene expression analysed by RNA sequencing. This will reveal transcriptomic changes in AT/RT which are induced by communication with the healthy brain, some of which will be putative therapy targets. The Tumoursphere Matrix model will finally be used as a screen to assess a library of drug compounds to identify repurposed therapeutics which impair tumour growth and invasion.

Environment:

The Children’s Brain Tumour Research Centre (CBTRC) brings together multidisciplinary researchers from clinical, translational and basic science arenas focused upon testing hypotheses generated by the clinical needs of the child or young person, presenting with a tumour of the central nervous system. The Centre links researchers from ten departments across the University and Nottingham University Hospital Departments conducting clinical and scientific research directed at increasing our understanding of the biological nature of childhood brain tumours and using this knowledge to optimize the health outcomes for the child and family.

CBTRC is housed within the University of Nottingham’s flagship Biodiscovery Institute (BDI). The recently completed £23M expansion that opened in Dec 2019 extends BDI to a £100M interdisciplinary complex of four interconnected buildings at the heart of main campus to house nearly 1000 academic, clinical and support staff, as well as very strong postgraduate student representation.

The PhD project will be supervised by Dr. Ruman Rahman (Associate Professor of Molecular Neuro-Oncology) and Prof. Richard Grundy (Professor of Paediatric Neuro–Oncology and Cancer Biology).

Applicants should hold, or expect to hold, a first or upper second class degree in one of the following disciplines: Molecular/Cellular Biology, Genetics, Developmental Biology or Biochemistry. MSc graduates are also encouraged to apply. 

This studentship is available from October 2021 for a period of 3 years. Fees will be covered with a stipend of £15,009 per annum. The studentship is only available to UK students due to funding restrictions.

To apply, students should send a 2-page CV and cover letter to ruman.rahman@nottingham.ac.uk.

Please quote ref: MED1589

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