Location
Hammersmith, London

Hours
Full time

Salary
£37,476 - £39,470 per annum, inclusive of London Allowance

About the Role
We are seeking a talented structural biologist to join the DNA Motors group led by Professor Luis Aragon at the MRC Laboratory of Medical Sciences (LMS) and Imperial College London. This role focuses on a translational cryo-EM project studying Structural Maintenance of Chromosomes (SMC) complexes – cohesin, condensin and SMC5/6 – using cryo-EM, single-molecule biophysics, biochemical reconstitution and cell biology. The post-holder will lead the structural arm of a drug discovery programme targeting the cohesin subunit STAG1, a synthetic-lethal vulnerability in STAG2-mutant cancers such as bladder cancer, Ewing sarcoma and myeloid malignancies.
The role involves producing STAG1 and STAG1-containing cohesin complexes, determining cryo-EM structures of these assemblies alone and bound to screening hits, and using this structural information to define binding sites, validate hits and guide compound optimisation in collaboration with medicinal chemistry and drug discovery partners. The successful candidate will have hands-on expertise in single-particle cryo-EM and experience working with SMC protein complexes.

Main Duties / Key Responsibilities
- Express and purify recombinant STAG1, cohesin and related SMC complexes (insect cell and E. coli systems) for structural and biophysical studies
- Prepare, screen and optimise cryo-EM grids and collect cryo-EM data using local and national facilities
- Perform single-particle image processing, 3D reconstruction, model building and refinement, including fitting and validation of bound small molecules
- Determine structures of STAG1/cohesin complexes with screening hits to define binding modes and support structure-guided hit development
- Contribute to hit validation using complementary biochemical and biophysical assays of compound binding
- Collaborate closely with medicinal chemists, the Drug Discovery Hub team and external partners, communicating structural results to inform compound design
- Plan and carry out research in accordance with project aims, taking initiative in research planning
- Maintain highly organised and accurate records of work, including structural data management and deposition
- Attend project and research group meetings, interact and collaborate with group members
- Contribute to write-up and publication of work in peer-reviewed journals
- Participate actively in academic activities of the LMS, including journal clubs and seminar presentations
- Present data at national and international meetings
- Form good working relationships with group members and collaborators
- Assist others and co-supervise students when required

Qualifications
- Essential: PhD in structural biology, biochemistry or a closely related field with a focus on cryo-EM (or a Masters with equivalent research experience)
- Desirable: First-author publication, preprint, or manuscript in preparation reporting cryo-EM structure(s)

Experience
- Essential: Evidence of planning and carrying out a research project
- Hands-on experience of single-particle cryo-EM, including sample and grid preparation, data collection and processing (e.g. RELION and/or cryoSPARC)
- Experience working with SMC protein complexes (cohesin, condensin or SMC5/6)
- Expression and purification of recombinant proteins, ideally large multi-subunit complexes
- Desirable: Atomic model building and refinement
- Experience with structure prediction and modelling tools (e.g. AlphaFold)
- Interest in and experience developing or implementing new techniques in the lab
- Evidence of actively contributing to or driving scientific collaborations

Knowledge and Skills
- Excellent written communication skills in English
- Strong knowledge of SMC complex architecture and mechanism
- Strong interest in applying structural biology to drug discovery and cancer therapeutics
- Demonstrated creative approaches to problem solving

Personal Skills and Qualities
- Ability to conduct reproducible research
- Ability to conduct detailed literature reviews
- Ability to develop and apply new concepts
- Creative problem-solving skills
- Excellent verbal communication skills and ability to engage with a wide range of people
- Ability to organise own work with minimal supervision and prioritise tasks to meet deadlines
- Willingness to work as part of a team with an open-minded and cooperative attitude
- Flexible approach to work and discipline with regard to confidentiality and security
- Willingness to work outside normal hours if project demands
- Willingness to undertake any necessary training for the role