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New probes for active enzymes

  • Full or part time
  • Application Deadline
    Tuesday, October 01, 2019
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Overview: A fully funded studentship is available with Prof. Joanna McGouran at Trinity College Dublin (http://joannamcgouran.wixsite.com/mysite). The project is in the field of chemical biology focusing on the synthesis of and testing of new modified peptides and proteins to study enzyme activity.

Background: Activity based probes-which mimic an enzyme substrate but contain a chemical trap are powerful tools in biological research. These probes advance many areas of biological and medical research including: Discovery of novel enzymatic activities, Inhibitor screening & Biomarker discovery. Deubiqtinating enzymes (DUBs), are a key class of enzyme in the cell, currently targeted for cancer therapy. In this project you will generate and study an entirely new class of probes for deubiquitinating enzymes (DUBs) building on recent discoveries within the laboratory. Probes will then be tested to determine the activity of deubiquitinating enzymes within a cellular context.

Project: Building on new functionality characterised within the laboratory this project will involve synthesis and testing a panel of new activity-based probes to examine deubiquitnating enzymes in a cellular environment. Generating the probes will involve a mix of organic synthesis and biochemical techniques followed by biochemical and biological evaluation of the probes created. As such this multidisciplinary project will provide excellent opportunities for you to gain a broad skill set developing expertise in protein purification and modification, synthetic chemistry, biochemical analysis, cell culture and proteomics techniques.

Research environment: You will work in a supportive interdisciplinary group in the Department of Chemistry. Our laboratory is located within the Trinity Biomedical Sciences Institute, a dynamic, multidisciplinary research environment. You will join a vibrant research community with world class research facilities and be given the opportunity to interact with complementary research groups and attend national and international conferences to present your results.

Requirements: Good university degree (1st or 2:1) in the field of Chemistry, Biochemistry or a related subject. Preference will be given to candidates with a demonstrable interest in chemical biology and/or significant lab experience. You must be highly motivated and able to work both independently and as part of a supportive team. Good knowledge of organic chemistry and an interest in research at the interface with biochemistry/molecular biology is required. Knowledge of protein expression and purification advantageous but not necessary as full training will be given to you in all aspects of the project.

Application: For further information or to apply please email a PDF copy of a brief cover letter and CV, to .

Funding Notes

Funding for this position would be sought from the Irish Research Council. For full call details see: View Website

References

Background reading:
McGouran, J.F., Gaertner, S.R., Altun, M., Kramer, H.B., and Kessler, B.M.: Deubiquitinating enzyme specificity for ubiquitin chain topology profiled by di-ubiquitin activity probes. Chemistry & biology, 2013, 20, 1447-1455.
McGouran, J.F., Kramer, H.B., Mackeen, M.M., di Gleria, K., Altun, M., and Kessler, B.M.: Fluorescence-based active site probes for profiling deubiquitinating enzymes. Organic & biomolecular chemistry, 2012, 10, 3379-3383.
Willems, L.I., Overkleeft, H.S. and van Kasteren, S.I.: Current developments in activity-based protein profiling. Bioconjugate Chemistry, 2014, 25, 1181-91.

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