School of Medicine, Dentistry
and Biomedical
Sciences
DEL Postgraduate Research Opportunity for
September 2011 – Subject to Funding
Centre for Cancer Research and Cell Biology
Predicting MCL-1 Addiction in Mesothelioma and sensitivity
to the BH3 Peptidomimetic, Obatoclax
Supervisors:
Dr. Dean Fennell (email d.fennell@qub.ac.uk)
Dr. Dan Longley (email d.longley@qub.ac.uk)
Candidates should have or expect to obtain a 2:1 or higher Honours degree or
equivalent in Microbiology, Biochemistry or other relevant Biology degree.
Further information is available on the School website at
http://www.qub.ac.uk/schools/mdbs/ (Click on Postgraduate Studentships).
Potential candidates are encouraged to contact the supervisor prior to submitting an
application.
Abstract
Evasion of programmed cell death (also known as apoptosis) is a hallmark of cancer. It is also a
major cause of resistance to cancer therapies. Mesothelioma is a particularly aggressive cancer
which is caused by asbestos, is increasing in incidence worldwide. We have found that a
frequently expressed gene called MCL1 is required for survival of mesothelioma cells, and
therefore represents a potential therapeutic Achilie’s heel. This translational research project will
be focused on understanding how addiction occurs at a biochemical level, and how to optimally
target this addiction using a novel small molecule inhibitor of MCL1 called obatoclax. We are
planning a large European multicentre clinical trial to evaluate its activity in mesothelioma,
however the mechanisms that determine its sensitivity, and importantly, its resistance in
mesothelioma are not known. In collaboration with the Wellcome Sanger Institute in Cambridge
and the Institute of Cancer Research in London, this project will aim to discover the key genetic
determinants of sensitivity and resistance to this drug. MCL1 which is encoded at 1q21.2 in the
genome, is one of the most amplified genes in cancer, and its amplification in mesothelioma could
confer hypersensitivity to obatoclax. Accordingly, the relationship between 1q21.2copy number
and obatoclax efficacy will be explored not only in cell lines, but also uniquely, in mesothelioma
cells obtained directly from patients. Finally, resistance genes identified by high throughput cell
screening and whole genome RNA interference screening will be explored as potential biomarkers
for tailoring therapy for patients with mesothelioma in a future clinical trial.
CLOSING DATE: Friday 11 February 2011
Eligibility for both fees and maintenance (£13,590 in 2010/11) depends on the applicants being either an ordinary
UK resident or those EU residents who have lived permanently in the UK for the 3 years immediately preceding
the start of the studentship. Non UK residents who hold EU residency may also apply but if successful may
receive fees only.