Chemical Biology/Chemical Proteomics PDRA - UOD1741

We are recruiting for an exceptional Chemical Biologist with experience in chemical probe design/synthesis and cellular biological profiling, to participate in a new academic-industrial global network supported by the Michael J Fox Foundation for Parkinson’s Research. The project aims to: (1) Explore and validate new approaches and novel modalities to target LRRK2; (2) Perform systematic mechanistic, structural and safety analyses to benchmark new inhibitors that emerge from this effort and (3) identify clinically relevant biomarkers for LRRK2 driven Parkinson’s disease that will facilitate the selection of patients who respond to LRRK2 inhibitor therapy. We aim to accelerate the development of Parkinson’s disease therapeutics. There will also be a significant opportunity to collaborate with pharmaceutical companies working in this area.

The appointed researchers will work as part of a newly established “LRRK2-team” that will be based within the state-of-theart laboratories within the University of Dundee’s Centre for Targeted Protein Degradation, and associated with the research groups of Alessio Ciulli, Will Farnaby and Peter Cossar (CeTPD, www.dundee.ac.uk/cetpd). The mission of this collaboration team will be centred on the design, synthesis, evaluation and optimization of induced-proximity small molecules targeting different regions of LRRK2. These molecules include protein degraders, known as PROTACs and molecular glues, that work by recruiting E3 ligases to induce intracellular ubiquitination and degradation of the target protein; and small molecule inducers/stabilizers of protein-protein interactions. The team will initially focus on three related and synergistic projects: 1) Discovery and optimization of PROTAC degraders of LRRK2, building on the learnings from chemical probe XL-01126 (Liu et al. J. Am. Chem. Soc. 2022); 2) Discovery of LRRK2-kinase targeting glue degraders; 3) Reactivating 14-3-3/LRRK2 binding as a strategy towards small molecule therapeutics.

Your priorities will include:

• Driving the design, synthesis and optimization of cellular chemical probes.
• Performing cellular mechanism of action studies to understand how molecular glue probes work, using state-of-the-art chemoproteomics and/or genetic interventions.

Who we’re looking for:

• A Ph.D. in chemical biology, medicinal chemistry, pharmaceutical sciences, or a related discipline
• Expertise in compound design and synthesis.
• Familiarity with routine cell culture and molecular biology techniques.
• Outstanding academic and/or industrial track record.
• Excellent interpersonal, communication and presentation skills.
• Capable of working in a diverse team, but able to plan and work independently.
• Exceptional time management, organisational and self-motivational skills.
• An open and collaborative approach to science.

The position is available from early October, and for a fixed-term of 2 years. The appointment will be made on University's Grade 7 (Spinal Point 29 -36) (£36,924- £45,163), dependent on experience. For further information about this position please contact Will Farnaby (w.farnaby@dundee.ac.uk), Alessio Ciulli (a.ciulli@dundee.ac.uk) or Peter Cossar (PCossar001@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. Opened since January 2023, CeTPD is a first of its kind Centre leading a number of internationally significant projects in the burgeoning new area of translational chemical biology and targeted protein degradation.

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