Postdoctoral Research Assistant (Targeting PPIs of E3 Ubiquitin Ligases with small molecules) - LS0568
College of Life Sciences, University of Dundee - Division of Biological Chemistry and Drug Discovery Full time, fixed term for 2 years in the first instance Salary range: Grade 7 (£30,434 - £37,394) Closing date for applications: Sunday, March 29, 2015 Description A postdoctoral position is available in the laboratory of Dr. Alessio Ciulli (http://www.lifesci.dundee.ac.uk/groups/alessio-ciulli/) to work on a project funded by the European Research Council (ERC). We are looking for a bright and motivated post-doctoral scientist to join a team of researchers broadly concerned with elucidating and characterizing Protein-Protein Interactions (PPIs) important to human biology and relevant to drug discovery, and targeting them using small molecules. The project will investigate the structure, assembly and druggability of protein surfaces and interfaces within heteromeric protein complexes of the human Cullin RING E3 Ubiquitin Ligases (CRLs). CRLs are a family of multi-subunit enzymes that target substrate proteins to the proteasome for degradation. CRLs play important roles in cancer, inflammatory processes and other diseases thus represent attractive yet underexplored targets for therapeutic intervention. You will study the structure, assembly and interactions of CRL complexes and components using X-ray crystallography and/or NMR spectroscopy, and other biophysical techniques. In addition, together with chemists within the Ciulli group, you will characterise the binding of novel small molecules against human CRLs and their component subunits and support the structure-based design of potent ligands using fragment-based design and peptidomimetics approaches. The project will combine protein expression, purification and crystallization, structure solution by X-ray crystallography, and structural, biophysical and biochemical techniques to study protein-ligand interactions and determine structure-activity relationships. The ultimate goal of the research is to unlock small molecule intervention on CRLs to elucidate their interactions, assembly and function in human biology and disease, as well as to validate their potential as new drug targets. For recent examples from our laboratory targeting the von Hippel-Lindau CRL see Galdeano et al., J. Med. Chem. 2014, 57, 8657-8663. http://dx.doi.org/10.1021/jm5011258 and studying the Suppressor of Cytokine Signalling (SOCS2) CRL see Bulatov et al., J. Biol. Chem. 2015, 290, 4178-4191. http://dx.doi.org/10.1074/jbc.M114.616664 The ideal candidate will posses or be able to demonstrate the following: • A PhD with outstanding academic track record and at least one first authored publication in an internationally recognized peer-reviewed journal (published or in press) • Strong background in protein purification and crystallography, X-ray data collection (in-house and at synchrotrons), structure solution and model refinement is essential • Experience with biophysical techniques studying protein-ligand interactions and in fragment-based / structure-based drug design is highly desirable. Experience with ligand-observed and/or protein-observed NMR spectroscopy would be advantageous • Some experience in biochemical techniques and cellular assays would be desirable but not necessary • Enthusiasm for Science • Independence • Capable of working in a team, but able to plan and work independently • Excellent written, oral and interpersonal communication skills and knowledge of the English language are essential Informal enquiries may be made to Dr. Alessio Ciulli, e-mail: a.ciu...@dundee.ac.uk. For more information on how to apply please visit: http://www.lifesci.dundee.ac.uk/vacancies/2015/feb/26/postdoctoral-research-assistant-targeting-ppis-e3-ubiquitin-ligases-small-0
