PhD Studentships in Epigenetics
Imperial Cancer Research UK Centre
Epigenetics Section, Division of Cancer,
Department of Surgery and Cancer
Imperial College London, Hammersmith Hospital Campus
Applications are invited from motivated individuals for a PhD studentship in Epigenetics,
focussing on the chemical biology of novel histone methyltransferase inhibitors. The post will
be based in Division of Cancer, Hammersmith Hospital Campus London. The primary
supervisors are Prof Robert Brown and Dr Nadine Chapman-Rothe, and collaboration with
Dr Matt Fuchter (Dept Chemistry) and Prof Eric Aboagye. Full details of the programme and
application forms can be found below.
The Polycomb Repressive Complex 2, PRC2, contains the histone methyltransferase EZH2,
which, together with EED and SUZ12, trimethylates histone H3 on Lysine 27 (H3K27me3)
and is associated with a repressive chromatin state 1. Many genes in cancer, including
tumour suppressor genes, are epigentically silenced by mechanisms associated with
H3K27me3 which can be independent of DNA methylation 2. Since H3K27me3 is somatically
inherited during cell division, this argues that it truly is an epigenetic mark that is maintained
and as such is a key target for reversing aberrant epigenetic silencing 3. There is increasing
evidence that the histone methyltransferase EZH2 could be an important target for inhibition
as a novel therapy strategy in cancer. EZH2 is over-expressed in many cancers and levels
of EZH2 correlate with poor prognosis 4,5. Furthermore, in animal models EZH2 has been
shown to be an important driver of metastasis and implicated in maintenance of tumour stem
cell cells 6.
In collaboration with Dr Matt Fuchter (Chemistry) and Prof Jim Snyder (Emory, USA) we
have identified novel small molecule inhibitors of histone methyltransferases (HKMTi). The
aims of the PhD project are to further characterise the biological activity of these
compounds, with the objectives of understanding their mechanisms of action and specificity
to HKMTi in tumour cells. As well as providing insight into this key mechanism of regulation
of gene expression, this will allow development of biomarkers which will aid the clinical
development of HKMT inhibitors.
The Epigenetics Unit’s strategic research goal is to study DNA methylation and chromatin in
four areas of translational cancer research: early diagnosis and risk prediction, prognostic
and drug resistance biomarker discovery, development of epigenetic therapies and ovarian
cancer stem cell biology. This research activity is based within a five star research institution
equipped with the latest technologies and facilities.
Imperial College has recently been awarded Cancer Research UK Centre status and the
position is funded from the Centre Training Grant. The studentship will form part of Molecular
Cell Biology and Immunology, Drug Discovery and Development theme within the centre. As
the UK’s first Academic Health Science Centre (AHSC) and largest NHS Trust, Imperial
College Healthcare stands at the forefront of the cancer research and patient care. Our
aspiration is to create a Cancer Research UK Centre that is globally competitive in the
development of treatments tailored to individual cancer patients. Imperial hosts an
impressive portfolio of cancer services and research and is committed to develop
interdisciplinary research programmes that translate basic, laboratory research into clinical
practice and point of care treatment.
Successful applicants will undertake a PhD, commencing in 2010. To be eligible, applicants
should hold or expect to obtain a first or upper-second class honours degree or equivalent in
a relevant biological science. In addition, for admission to a PhD research programme
Imperial College would normally expect you to hold or achieve a Master's degree.
Knowledge or experience in genetics, epigenetics or molecular medicine would be an
advantage.
The stipend for year 1 will be £ 17,500pa. Interested applicants should submit a curriculum
vitae, a personal statement and names of two referees. UK/EU citizens can apply: only
UK/EU student fees are available. For further information (and submission of CV etc) please
contact Prof Robert Brown: b.brown@imperial.ac.uk.
Closing date: 31st August 2010
References
1.
Cao, R. & Zhang, Y. Curr Opin Genet Dev 14, 155-64 (2004).
2.
Kondo, Y. et al. Nat Genet 40, 741-50 (2008).
3.
Margueron, R. et al. Nature 461, 762-7 (2009).
4.
Matsukawa, Y. et al. Cancer Sci 97, 484-91 (2006).
5.
Collett, K. et al. Clin Cancer Res 12, 1168-74 (2006).
6.
Min, J. et al. Nat Med 16, 286-94.