PhD In Chemical Biology/Medicinal Chemistry

Overview:  A fully funded studentship opportunity 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 probes to study enzymatic 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. In this project you will synthesise and study an entirely new class of probes, building on recent discoveries within the laboratory. Probes will then be tested to determine their activity and specificity within a cellular context, prior to developing new inhibitor screening assays to accelerate drug discovery.

Project: Building on recent radical protein trapping methodologies developed within the laboratory, this project will involve synthesis and testing a panel of new activity-based probes. 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 (1^st or 2:1) in the field of Chemistry 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 multistep organic synthesis and/or biochemical assays advantageous but not necessary as full training will be given to you in all aspects of the project.

Application: Funding will include 4 years stipend (€22,000 p.a.), EU fees and consumables, to begin September 2024. The PhD will be part of the Dublin Chemistry Graduate Programme. For further information or to apply please email a PDF copy of a brief cover letter and CV, to jmcgoura@tcd.ie by Midday Tuesday 7^th May.

Background reading:

Taylor, NC., Hessman, G, Kramer, HB., McGouran, JF., Probing enzyme activity - a radical approach, Chemical Science, 2020, 11, 2967

Willems, L.I., Overkleeft, H.S. and van Kasteren, S.I.: Current developments in activity-based protein profiling. Bioconjugate Chemistry, 2014, 25, 1181

Conole, D., Cao, F., am Ende, C. W., Xue, L., Kantesaria, S., Kang, D., Jin, J., Owen, D., Lohr, L., Schenone, M.,  Majmudar, J.D.,  Tate, E. W., Discovery of a Potent Deubiquitinase (DUB) Small Molecule Activity-based Probe Enables Broad Spectrum DUB Activity Profiling in Living Cells, Angewandte, 2023, 1433