Senior Laboratory Research Scientist in Chemical Biology

Senior Laboratory Research Scientist in Chemical Biology Reports to: Head of Chemical Biology STP This is a full-time, fixed term (three-year) position on Crick terms and conditions of employment The program The Molecular Glue (MG) Discovery Partnership represents an exciting research partnership between the Francis Crick Institute and Imperial College working in close collaboration with AstraZeneca. Our aim is to unlock new principles of MG discovery , reveal novel MG biology , and exploit the revolutionary therapeutic potential of molecular glue degraders by developing systematic approaches to exploit endogenous protein degradation pathways to target intractable disease-relevant proteins or protein complexes. By combining fundamental biology with high throughput screening, protein engineering, proteomics and chemical biology approaches, we seek to discover and develop new molecular glues to induce degradation of proteins of interests through the ubiquitin proteasome system or autophagy. This work is funded through a 5-year, £11.2M public-industry initiative, and brings together a team of 12 postdoctoral biochemists, cell, structural and chemical biologists and 3 PhD students working across a dozen laboratories and scientific technology platforms (STPs) at the Francis Crick Institute and Imperial College London, and a team of scientists with complementary industrial expertise engaged in the Partnership at AstraZeneca. https://www.imperial.ac.uk/news/245036/new-partnership-will-molecular-glues-tackle/ The Prosperity Partnership provides an opportunity for scientists to work at the interface between academia and pharma to discover and develop future therapies. This initiative gives scientists the prospect of gaining experience in both academic and pharmaceutical settings, as well as learning how to collaborate effectively and build strong connections between the two institutions. Chemical Biology Scientific Technology Platform The position is within the Chemical Biology Scientific Technology Platform (STP), a newly formed and expanding interdisciplinary group, at the Francis Crick Institute. The STP collaborates with researchers at the Crick to apply chemistry to explore biological questions, working at the cutting edge of biomedical science in disciplines such as cancer, infectious disease, immunology, neurology, and developmental biology. Our research focuses on the design, synthesis and application of chemical tools to explore the function and disease-relevance of proteins, pathways and phenotypes, paving the way to translating biological insights into clinical impact. Role Summary We are seeking ambitious and creative chemical biologist to join the the Chemical Biology STP at the Francis Crick Institute, with a key role in our Molecular Glue (MG) Discovery EPSRC Prosperity Partnership with AstraZeneca and Imperial College London. Your role will be to drive discovery and medicinal chemistry optimisation of novel molecular glues, based on starting points discovered through a wide range of biochemical, computational, structural and cellular screening technologies spearheaded by the Partnership. In collaboration with the full team of the Partnership, you will determine the detailed molecular mechanism of action of these glues and unveil new modes of MG degrader activity across diverse targets and effectors (UPS, autophagy). Both the Partnership and the STP are highly multidisciplinary, encompassing scientists from a variety of backgrounds in an integrated academia-industry setting (chemical biology, cell biology, proteomics, cancer biology, drug discovery, etc.). The successful applicant will be an independent thinker, with the ability to initiate and run projects, co-lead collaborative teams, and engage in co-supervision of Master and PhD level students. We are looking for candidates who can thrive in this dynamic and creative environment and take optimal advantage of the many training opportunities it provides. Key responsibilities will include: Medicinal chemistry validation and optimisation of hits to generate high quality molecular glue tool compounds (using physicochemical properties, generation and analysis of on-target SAR in biophysical, biochemical and cell-based assays, selectivity profiling, structure-based design etc). Collaboration with other STPs and Research Groups within the Partnership to characterise the molecular mechanism of action of small molecule glues, applying biophysical assays, crystallography, cryoEM and omics profiling. Design and prosecution of synthetic routes to access small molecule target compounds. Continuous professional development as an active member of the scientific community by writing scientific articles, as well as presenting research findings at scientific meetings and/or conferences. Key experience and competencies The post holder should embody and demonstrate our core Crick values: Bold, Open, and Collegial, in addition to the following: Essential: PhD (or equivalent experience level) in a relevant discipline such as chemical biology, medicinal chemistry or synthetic organic chemistry. A strong track record of developing innovative solutions to chemical biology or medicinal chemistry questions in academic or industrial research, supported by publications in peer-reviewed journals. A deep knowledge of Medicinal Chemistry principles for the design and optimisation of small molecule ligands. Excellent knowledge of theoretical and practical synthetic chemistry, combined with a track record of high laboratory productivity. Independent capability and creativity in idea generation and experimental design Excellent written and oral communication skills. Ability to mentor junior researchers, and to set and attain research objectives as part of a multidisciplinary team Desirable: Design, generation and/or molecular mechanism of action studies for proximity-induced pharmacology (for example molecular glues, PROTACs, etc.) Experience in structure-guided design of small molecule ligands Experience in applications of chemical proteomics Experience of screening DNA-encoded libraries About Us At the Crick, we conduct research at the forefront of biomedical research. We combine rigour with an open and collaborative culture, and are outward-looking, reflecting our status as a partnership of six organisations aiming to pool knowledge, ideas and resources. We have a wide research portfolio with no divisions or departments, bringing biomedical researchers together with clinicians, physical scientists and applied scientists from our pharmaceutical partners. We aim to attract the most talented researchers and support them to tackle innovative research questions. Our science technology platforms provide our researchers with access to state-of-the-art technology and expertise. We provide an excellent learning environment with dedicated education programmes in public engagement with science, education and personal development, and a postdoc training programme that prepares scientists for leadership roles in science. All offers of employment are subject to successful security screening and continuous eligibility to work in the United Kingdom. Find out what benefits the Crick has to offer: For more information on our great pay and benefits package please click here: https://www.crick.ac.uk/careers-and-study/life-at-the-crick/pay-and-benefits Equality, Diversity & Inclusion: We welcome applications from all backgrounds. We are committed to providing equal employment opportunities, regardless of ethnicity, nationality, gender, sexual orientation, gender identity, religion, pregnancy, age, disability, or civil partnership, marital or family status. We particularly welcome applications from people who are Minority Ethnic as they are currently underrepresented in the Crick at this level. Diversity is essential to excellence in scientific endeavour. It increases breadth and perspective, leading to more innovation and creativity. We want the Crick to be a place where everyone feels valued and where diversity is celebrated and seen as part of the foundation for our Institute’s success. The Crick is committed to creating equality of opportunity and promoting diversity and inclusivity. We all share in the responsibility to actively promote dignity, respect, inclusivity and equal treatment and it is our aim to ensure that these principles are reflected and implemented in all strategies, policies and practices. Read more on our website: https://www.crick.ac.uk/careers-and-study/life-at-the-crick/equality-diversity-and-inclusion