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Objective: The available post is for a Postdoctoral Position to support the investigator’s research programme in Cancer Biology and Apoptosis

Reporting to: Prof Jochen Prehn (Principal Investigator)

Project background and description: The Centre for Systems Medicine and the Department of Physiology and Medical Physics investigate apoptosis signalling pathways and stress pathways and their role as prognostic markers and novel targets for the treatment of cancer. It is funded by Science Foundation Ireland, the European Union, as well as the Irish Health Research Board.

In a study funded by the Health Research Board (APO-COLON), we identified the proteasomal subunit Rpt4 to be elevated in colorectal cancer tissue when compared to matched normal tissue. Furthermore, in vitro as well as in vivo xenograft studies using gene silencing approaches suggested that inhibition of Rpt4 function is an attractive new target for the treatment of cancer.

The project aims to further evaluate the future potential of targeting Rpt4 expression as therapies for cancer. Studies include: A) Analysis of Rpt4 expression in tumour samples to examine whether any acute changes can be observed in Rpt4 expression following neoadjuvant radiochemotherapy or during metastatic progression. B) In vitro characterization experiments investigating the specificity of Rpt4 inhibition towards cancer cell survival. C) Identifying small molecule inhibitors of Rpt4, including the development of high-throughput assays.

Further duties of this post will include:
• Complying with statutory legislation and Department rules and requirements in furtherance of your own and general staff welfare and safety
• Undergoing programmes of training and development as may be required from time to time
• Representing the best interests of the Department/RCSI at all times
• Performing such other duties as may be required from time to time.

Availability: The position will be available from October 1st.

Person Specification: The candidate should have a PhD in Biochemistry, Pharmacology or Cell Biology, ideally in the field of cancer biology, apoptosis, or proteasomal function. (S)he should have significant research experience in the subject areas described as documented by publications. (S)he needs to be able to independently plan and conduct the research project and to integrate into a interdisciplinary research environment. Grant writing skills and experience in the supervision of undergraduate students in research is of advantage.

Salary: The successful candidate will be appointed on the salary scale for postdocotrates at a point commensurate with qualifications and experience.

Application procedure: Please send a CV and names of at least two referees plus accompanying documentation (such as certificates, publications) to jprehn@rcsi.ie

Closing date: Applications must be received by Friday 21st of September, 2012.

Other information:
http://www.systemsmedicineireland.ie/
Recent publications:
Hector S, Conlon S, Schmid J, Dicker P, Cummins RJ, Concannon CG, Johnston PG, Kay EW, Prehn JH. Apoptosome-dependent caspase activation proteins as prognostic markers in Stage II and III colorectal cancer. Br J Cancer. 2012 Apr 24;106(9):1499-1505.
Laussmann MA, Passante E, Hellwig CT, Tomiczek B, Flanagan L, Prehn JH, Huber HJ, Rehm M. Proteasome inhibition can impair caspase-8 activation upon submaximal stimulation of apoptotic tumor necrosis factor-related apoptosis inducing ligand (TRAIL) signaling. J Biol Chem. 2012 Apr 27;287(18):14402-11. Epub 2012 Mar 9.
Hector S, Rehm M, Schmid J, Kehoe J, McCawley N, Dicker P, Murray F, McNamara D, Kay EW, Concannon CG, Huber HJ, Prehn JH. Clinical application of a systems model of apoptosis execution for the prediction of colorectal cancer therapy responses and personalisation of therapy. Gut. 2012 May;61(5):725-33.
McCawley N, Conlon S, Hector S, Cummins RJ, Dicker P, Johnston PG, Kay EW, McNamara DA, Prehn JH, Concannon CG. Analyzing proteasomal subunit expression reveals Rpt4 as a prognostic marker in stage II colorectal cancer. Int J Cancer. 2012 Aug 15;131(4):E494-500.
Tuffy LP, Concannon CG, D’Orsi B, King MA, Woods I, Huber HJ, Ward MW, Prehn JH. Characterization of Puma-dependent and Puma-independent neuronal cell death pathways following prolonged proteasomal inhibition. Mol Cell Biol. 2010 Dec;30(23):5484-501.
Concannon CG, Koehler BF, Reimertz C, Murphy BM, Bonner C, Thurow N, Ward MW, Villunger A, Strasser A, Kögel D, Prehn JH. Apoptosis induced by proteasome inhibition in cancer cells: predominant role of the p53/PUMA pathway. Oncogene. 2007 Mar 15;26(12):1681-92.