France :PhD Position In Cascade Profiling Of The Ubiquitin Proteasome System In Prostate Cancer
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PhD Position in Cascade Profiling of the Ubiquitin Proteasome System in Prostate Cancer, France Please mention www.bunchbay.us when applying for this position Ph.D. project: Cascade profiling of the ubiquitin proteasome system in prostate cancer A position is available for a motivated Ph.D. student to study the involvement of the ubiquitin-proteasome system in prostate cancer. The project relies on the application of RNAi screening and chemical proteomics to identify proteins implicated in cancer progression. Institution: Biomicslaboratory, Commissariat a l’Energie Atomique et aux Energies Alternatives (CEA), Grenoble, France Supervisor: Dr. M. Balakirev Application Deadline:April 2012. Funding Availability: Three-yearstudentship, Irtelis CEA, ~2000€/month Prostate cancer is the most common malignancy among men and is the second-leading cause of male cancer death in Western societies.The morbidity of this cancer results from the high incidence of an androgen-refractory form of the disease for which no treatment is available. This underlines the urgent need for new therapeutic strategies, though the only drug targets exploited to date involve the pathways of androgen signaling. Clearly, the discovery of alternative targets is the bottleneck for development of new prostate cancer treatments. from research over the past several years have led us to suggest a promising new target, the ubiquitin-proteasome system(UPS). The UPS targets proteins for degradation by the proteasomethroughthe covalentattachment of the small protein ubiquitin (”ubiquitylation”). This degradative process provides a means for rapid restructuring of protein networks and switching in cell fate, and as such, functions during cell cycle progression, differentiation,apoptosis etc. Ubiquitylation also has multiple non-proteolytic functions such as regulation of DNA repair and intracellular traffic. In addition, more than 10 other ubiquitin-like modifiers share a mechanism similar to that of ubiquitininsubstrate modification and subsequent cell regulation. Ubiquitylation, as mediator of molecular turnoverin a majority of key cellular functions, is tightly controlled. When deregulated,the UPS has been implicated in malignant transformation, and a number of individual components of the pathway have been identified as being directly involved in cancer.Expanded identification of these componentsand characterization of their drug susceptibility is therefore of clinical importance as it may lead to the discovery of new therapeutic targets. In the course of this Ph.D. project, we willdevelopand apply a novel systematic approach tothe functional profiling of the UPS in cancer. This approach, which we have named “cascade profiling”, takes as its starting pointthe cascade organization of the UPS and uses its hierarchical mode of function to facilitate the identificationof individual components. By combining high-throughputRNAi screening and activity-based proteomic profiling we hope to delineate ubiquitin conjugation pathways involved in prostate cancer. Specifically, we will apply cascade profiling to define UPS protein networks at various stages in the development of prostate cancer;e.g., cellular models for normal prostate epithelium, benign prostatic hyperplasia, and staged cancers, including androgen-refractoryforms. The main objectives are: (i) to identify UPS enzymes critical for cancer progression and the transition to androgen-refractory form; (ii) to understand the molecular mechanisms of their function; (iii) to evaluate their potential as cancer drug targets.The Ph.D. student will: 1) primarily focus on design and synthesis of new proteomic probes and their use for UPS profiling; and 2) participate in RNAi experiments, analysis of the protein interaction networks, and biochemical characterization of the identified UPS components. The research will be carried out in the Biomics laboratory/CEA-Grenoble/France (cancer cell lines, RNAi screening, synthesis of proteomic probes, UPS profiling) in close collaboration with the LEDyP laboratory/CEA-Grenoble/France(MS-proteomics) and Pr. Wilkinson’s laboratory/Emory University/USA (synthesis of proteomic probes, UPS profiling). The candidate will be enrolled in the Ph.D. program at the University of Grenoble (Universite Joseph Fourier). Profile of candidate‘s qualification: The successful candidate should have a qualified M.Sc. or equivalent degree in the life sciences, preferably chemical biology, biochemistry, molecular biology, or in a related field. The candidate will also deal withorganic synthesis. Prior experience with ubiquitin biochemistry and UPS is an advantage. In-depth knowledge of modern methods in protein biochemistry or molecular cloning and production of recombinant proteins would be appreciated as well as a basic knowledge of organic chemistry.The Irtelisstudentship is highly competitive and requires that candidates have good grades, high test scores, and strong letters of recommendation. Contact: To apply, please send a brief statement describing your motivation for the project, curriculum vitae, copies of your academic qualifications and the contacts of three referees to Dr. M. Balakirev (maxim.balakirev[ at ]cea.fr) Please mention www.bunchbay.us when applying for this position |
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