University of Dundee

Postdoctoral Research Assistant (Chemical Probes for E3 Ubiquitin Ligases)

Unit: 
Biological Chemistry and Drug Discovery
Job Reference: 
SLSC0756
Closing Date: 
Monday, August 24, 2020
Salary: 
Grade 7 (£32,817 - £40,322)

The School of Life Sciences at the University of Dundee is a world-class academic institution with a reputation for the excellence of its research, its high quality teaching and student experience, and the strong impact of its activities outside academia. With 900 staff from over 60 countries worldwide the School provides a dynamic, multi-national, collegiate and diverse environment with state-of-the-art laboratory, technology and teaching facilities.

We are seeking an ambitious and scientifically-creative postdoctoral researcher with experience in biophysics and/or structure-based drug design to work in the laboratory of Alessio Ciulli at the Dundee’s School of Life Sciences, Division of Biological Chemistry and Drug Discovery, under the auspices of a new Protein Degradation Centre. The successful candidate will join a diverse, fast-paced and collaborative team based within the Ciulli group at Dundee to contribute to multi-disciplinary projects as part of EUbOPEN (https://www.eubopen.org/). EUbOPEN is a multi-partner, highly collaborative consortium recently established and funded for 5 years by the Innovative Medicines Initiative (IMI) to enable and unlock biology in the open.

Your priorities will include:

The successful candidate will be involved in the design, development and validation of small-molecule binding ligands and chemical probes (drug-like inhibitors) that target E3 ubiquitin ligases, multi-protein enzyme complexes that tag substrate proteins with ubiquitin. The successful candidate will be involved in the development and application of fragment-based screens; peptide binding and displacement assays in vitro; cellular target engagement assays; as well as applying biophysical and structural techniques such as X-ray crystallography and NMR spectroscopy to study protein-ligand and protein-protein interactions down to molecular detail.

The ultimate goal of the project is to qualify high-affinity, selective and cell-active small molecules as tool compounds to investigate the E3 ligase target’s biology, and as starting points for conjugation into bifunctional degrader molecules, also known as proteolysis-targeting chimeras (PROTACs), co-opting novel E3 ligases for targeted protein degradation.

For more information on our laboratory see https://www.lifesci.dundee.ac.uk/groups/alessio-ciulli/

For further information on recent research on structure-based targeting of E3 ubiquitin ligases and small-molecule E3 ligase ligands development by the Ciulli group see Kung et al. Nat. Commun. 2019; Castro & Ciulli, Chem. Commun. 2019; and Lucas et al. J. Med. Chem. 2018.

Who we’re looking for:

This is a unique opportunity to gain experience in world-leading, collaborative and cutting-edge research in one of the hottest areas of modern translational chemical biology and drug discovery within an academic setting with an open-science ethos.

Requirements:

  • A Ph.D. in structural biology, biophysics, biochemistry, chemical biology, pharmaceutical sciences, or a related discipline
  • Strong background in biophysics, chemical biology or structural biology, with an emphasis on structure-based drug design.
  • Strong skills in molecular biology (construct design, cloning etc.), protein expression and purification, and assay development
  • Excellent interpersonal, communication and presentation skills
  • An open and collaborative approach to science

Preferred skills:

  • Experience with fragment-based screening and structure-based drug design
  • Experience with multi-protein complexes and with targeting protein-protein interactions
  • Outstanding academic or industrial track records
  • Capable of working in a diverse team, but able to plan and work independently
  • Exceptional time management, organisational and self-motivational skills

Apply Here

The post is available for an immediate start and is for 2 years in the first instance.  This term may be extendable dependent on project progress and funding.

The Biological Chemistry and Drug Discovery Division and Drug Discovery Unit operate on an external funding basis. The Principal Investigators within these units are highly successful in securing external funding for their multi-disciplinary and highly collaborative research and activities. 

Appointment as a Postdoctoral Research Assistant on the Grade 7 salary scale is dependent upon you having been awarded a PhD. An appointment may be considered if you are shortly expected to be awarded a PhD. The initial appointment would be made as a Research Assistant on the Training Grade 7 salary scale (Spinal Point 25 - 28 £29,176 - £31,866).

Informal enquiries may be made to Professor Alessio Ciulli, e-mail: a.ciulli@dundee.ac.uk

The new Protein Degradation Centre is part of a growing Life Sciences Innovation District, an ecosystem of organisations and people within the life sciences sector in Dundee driving innovation and local economic growth. The Centre has a track record of redefining new models of research in translational chemical biology, such as innovative academia-industry collaborations (Boehringer Ingelheim, Eisai amongst others) and spin-out companies (Amphista therapeutics).

The Protein Degradation Centre is located in a beautiful setting overlooking the estuary of the River Tay. They are embedded within the University of Dundee’s School of Life Sciences, one of the premier research centres in the world recently assessed as the top UK University for Life Sciences research in the 2014 Research Excellence Framework (REF). The University of Dundee main city-centre campus is at the heart of Dundee - an up-and-coming, friendly, compact and affordable city with a rich heritage in design and technology. Just a short walk from the V&A Museum of Design Dundee, we’re close to both the train and bus stations. http://www.lifesci.dundee.ac.uk/

The EUbOPEN consortium is an Innovative Medicines Initiative (IMI) funded project to enable and unlock biology in the open. The consortium comprises 22 different partner organizations, including universities, research institutes, European Federation of Pharmaceutical Industries and Associations (EFPIA) members, and one small and medium-sized enterprise (SME). Goethe University Frankfurt and Boehringer Ingelheim are jointly leading the EUbOPEN consortium. Other partner organizations are Bayer AG, Diamond Light Source, EMBL-EBI, ETH Zürich, Fraunhofer IME, Georg-Speyer-Haus, Karolinska Institutet, Leiden University Medical Center, McGill University, Ontario Institute for Cancer Research, Pfizer, Royal Institute of Technology, Servier, the Structural Genomics Consortium, Takeda, University of Dundee, University of North Carolina, University of Oxford, and University of Toronto. EUbOPEN will run for five years and will have a total budget of 65.8 million euros covered by a grant from the IMI and cash and in-kind contributions from the EFPIA companies, IMI Associated Partners and non-EU partners.

The IMI is Europe's largest public-private initiative aiming to speed up the development of better and safer medicines for patients. IMI supports collaborative research projects and builds networks of industrial and academic experts in order to boost pharmaceutical innovation in Europe. IMI is a joint undertaking between the European Union and the European Federation of Pharmaceutical Industries and Associations (EFPIA).

The diversity of our staff and students helps to make the University of Dundee one of the top universities in the UK. Family friendly policies, staff support networks for BME and LGBT staff, membership of Athena Swan and Stonewall, as well a full range of disability services, create an enjoyable and inclusive place to work.