Download PhD studentship - Development of preclinical models of High Grade

PhD studentship - Development of preclinical models of High Grade Serous
Ovarian Cancer heterogeneity and response.
The Cancer Research UK Cambridge Institute (CRUK CI) is a joint venture between the Charity, Cancer
Research UK, and the University of Cambridge. The Institute has excellent state-of-the-art facilities and
research ranges from basic cancer biology and computational biology through to translational research and
clinical application.
Graduate students play a pivotal role in the continuing success of our research programmes and gaining a
studentship in the Institute is an excellent opportunity to start a research career in an environment
committed to training outstanding cancer research scientists of the future.
Dr James Brenton, Head of the Functional Genomics of Ovarian Cancer group, wishes to appoint a student
to work on the project entitled: Development of preclinical models of High Grade Serous Ovarian Cancer
heterogeneity and response.
Project details
High grade serous ovarian cancer (HGSOC) is the most common and lethal gynaecological cancer. A major
barrier to improving treatment choices for HGSOC is the extreme genomic heterogeneity observed between
cases and within a tumour [1]. Ubiquitous TP53 loss and common involvement of DNA repair pathways such
as BRCA1 and BRCA2 is accompanied by numerical and structural chromosomal abnormalities in HGSOC.
We proposed that early loss of TP53 may be permissive for the development of a wide range of mutator
phenotypes in HGSOC, and may explain its genomic diversity and intratumoural heterogeneity [2, 3]. Using
whole genome sequencing we showed how a novel mutator phenotype in HGSOC causes ongoing and
divergent evolution [4] and are now undertaking large scale sequencing studies on women with relapsed
disease.
Currently available HGSOC cell lines do not adequately model genetic and phenotypic heterogeneity of
HGSOCs. However, in vivo preclinical models were observed to maintain intratumoural heterogeneity and
functional characteristics of clinical patient samples [5]. While this is promising, in vivo preclinical models are
not appropriate for large scale discovery research using high throughput screening.
This project will develop preclinical models, such as short-term cultures of patient derived xenograft HGSOC
cells to perform mechanistic studies and in vitro drug screens [5]. It will test therapies against genomic
hallmarks of HGSOC, specifically centrosome amplification and metabolic vulnerabilities.
This project is ideal for candidates seeking experience in transitional research, who will work in a
multidisciplinary team of clinicians and scientists.
For up to date information about the research group, including their most recent publications, please see
their website at: http://www.cruk.cam.ac.uk/research-groups/brenton-group
Preferred skills/knowledge
Applicants should have excellent communication and team working skills. A strong background in genomics
and computational methods would be an advantage. The project will provide strong training in next
generation sequencing, bioinformatic analysis and experimental design.
Funding
This project is funded by a Cancer Research UK studentship that includes full funding for University and
College fees and a stipend of £19,000 per annum.
Eligibility
No nationality restrictions apply to Cancer Research UK funded studentships. Applications are invited from
recent graduates or final year undergraduates who hold or expect to gain a first/upper second class degree
(or equivalent) in a relevant subject from any recognised university worldwide.
How to apply
Please send your academic CV and a covering letter as attachments [email protected]
Your CV should include a list of the examinations taken at undergraduate level and if possible, your
examination results. Also the names and contact details of two academic referees who have agreed to act on
your behalf.
Your covering letter should explain why you wish to be considered for the studentship and which qualities
and experience you will bring to the role. Please also state how you learned of the studentship.
Deadline
The closing date for applications is 30 November 2016.
Further reading:
1.
Schwarz, R.F., et al., Spatial and temporal heterogeneity in high-grade serous ovarian cancer: a
phylogenetic analysis. PLoS Med, 2015. 12(2): p. e1001789.
2.
Cooke, S.L. and J.D. Brenton, Evolution of platinum resistance in high-grade serous ovarian cancer.
Lancet Oncol, 2011. 12(12): p. 1169-74.
3.
Cooke, S.L., et al., Genomic analysis of genetic heterogeneity and evolution in high-grade serous
ovarian carcinoma. Oncogene, 2010. 29(35): p. 4905-13.
4.
Ng, C.K., et al., The role of tandem duplicator phenotype in tumour evolution in high-grade serous
ovarian cancer. J Pathol, 2012. 226(5): p. 703-12.
5.
Bruna, A., et al., A Biobank of Breast Cancer Explants with Preserved Intra-tumor Heterogeneity to
Screen Anticancer Compounds. Cell.
Please quote reference SW10307 on your application and in any correspondence about this vacancy.
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