The University of Sheffield
Faculty of Medicine, Dentistry & Health
Department of Oncology
Next-Generation Sequencing into practice: Identifying functionally important aberrations in
NF-1 (Neurofibromin-1)
Supervisors: Dr Gill Wilson, Head of Oncology Genetics for Sheffield Diagnostics
Genetics Service and Dr Sarah Danson, Reader in Medical Oncology from the Academic
Unit of Clinical Oncology, University of Sheffield.
Project:
In human biology, Neurofibromin (NF-1) is a tumour suppressor, linked to regulation
of the Ras/Raf/MEK/ERK pathway. It is a large gene, with a high number of low frequency
genetic variants. Somatic mutations in NF-1 have been reported in Non-small cell lung
cancer (NSCLC) patients and we hypothesise that NSCLC clinical samples would provide
enriched set of NF-1 genetic variants that can be utilised to assess linkage of a
variety of genetic variants to activation or inhibition of cellular pathways. A
complete understanding of the functional consequences of somatic NF-1 aberrations is
lacking, particularly at the level of protein expression and intracellular pathway(s)
regulation. Linkage of specific genetic aberrations to changes in protein expression
and MEK pathway activation in individual subjects is novel and of wide scientific
interest.
Recent technological advances in genetic testing, including next-generation sequencing
(NGS) are creating ever increasing volumes of genetic data, but in many cases there
is minimal data linking observed genetic polymorphisms with functional outcomes at
the cellular or whole organism level. Additionally, the analytical validation,
including reproducibility and sensitivity has often not been well established for NGS
platforms.
We are advertising for a CASE studentship from BBSRC and AstraZeneca. This will provide
doctoral training to develop expertise in NGS sequencing and variant annotation to a
extremely high standard of analytical robustness. In addition, they will be trained
in cellular techniques of IHC, mRNA analysis and bioinformatics to identify cellular
pathways activated in subjects carrying different somatic variants of a tumour
suppressor gene. The skills developed will equip the student for a future career in a
wide range of biomedical and biotechnology settings.
Entry Requirements:
Candidates must have a first or upper second class honors degree or significant
research experience.
Enquiries:
Interested candidates should in the first instance contact Gill Wilson
(Gill.Wilson@sch.nhs.uk or 0114 271 7016 or Sarah Danson (s.danson@sheffield.ac.uk or
0114 226 5235).
How to apply:
Please complete a University Postgraduate Research Application form and attach at
least two references to your application. To complete the application form please
visit: www.shef.ac.uk/postgraduate/research/apply.
Please clearly state ‘Dr Danson’ and select ‘Oncology’ as the department.
Website: http://www.shef.ac.uk/oncology
Closing date: Monday 16th June 2014