Research Technician

Research Technician - Cryo-EM / Structural Biology LMS2961
£37,476 - £39,470 per annum, inclusive of London Allowance
12-month Fixed term Full time Location: Hammersmith London

Overall purpose:

We are looking for a talented structural biologist to join the DNA Motors group headed by Professor Luis Aragon at the MRC Laboratory of Medical Sciences (LMS) and Imperial College London, working on a translational cryo-EM project.

The DNA Motors group studies the Structural Maintenance of Chromosomes (SMC) complexes - cohesin, condensin and SMC5/6 - using cryo-EM, single-molecule biophysics, biochemical reconstitution and cell biology. Through the LMS-Imperial Drug Discovery Hub, we are running 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 post-holder will lead the structural arm of this programme during the screening and hit-development phase: 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 together with our medicinal chemistry and drug discovery partners.

The ideal candidate will have a background in structural biology, with hands on expertise in single particle cryo EM and prior experience working on SMC protein complexes.

Main duties / key responsibilities:

• Express and purify recombinant STAG1, cohesin and related SMC complexes (e.g. 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
• Carry out 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
• Work closely with medicinal chemists, the Drug Discovery Hub team and external partners, communicating structural results to inform compound design
• To plan and carry out research in accordance with the project aims
• Take initiatives in the planning of research
• Conduct and plan own scientific work with appropriate supervisor
• Maintain highly organised and accurate records of work, including structural data management and deposition
• To attend project and related research group meetings
• To interact and collaborate with group members
• Contribute to write up and publication of work in peer reviewed journals
• To take an active part in the academic activities of the LMS
• To attend and contribute to journal clubs and seminar presentations
• Presentation of data at national and international meetings
• To form good working relationships with other members of the group as well as internal and external collaborators
• To assist others and co supervise students when required

Education / Qualifications / Training required (will be assessed from application form): Essential:

• A PhD in structural biology, biochemistry or a closely related field with a focus on cryo EM (or a Masters with equivalent research experience)

Desirable:

A first author publication, preprint, or manuscript in preparation reporting cryo EM structure(s)

Previous work experience required (will be assessed from application form and at interview): Essential:

• Evidence that the candidate can plan and carry out a research project
• Hands on experience of single particle cryo EM, from sample and grid preparation through data collection and processing (e.g. RELION and )
• 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 proven experience of developing or implementing new techniques in the lab
• Evidence of actively contributing to or driving scientific collaborations

Knowledge and experience (will be assessed from application form and at interview): Essential:

• Excellent written communication skills in English
• Strong knowledge of SMC complex architecture and mechanism
• A strong interest in applying structural biology to drug discovery and cancer therapeutics
• Demonstration of creative approaches to problem solving

Personal Skills / Behaviours / Qualities (will be assessed at the interview): Essential:

• Ability to conduct reproducible research
• Ability to conduct a detailed review of recent literature
• Ability to develop and apply new concepts
• Creative approach to problem solving
• Excellent verbal communication skills in English and the ability to deal with a wide range of people
• Ability to organise own work with minimal supervision
• Ability to prioritise own work in response to deadlines
• Willingness to work as part of a team and to be open minded and cooperative
• Flexible attitude towards work
• Discipline and regard for confidentiality and security at all times
• Willingness to work out of normal working hours if the requirements of the project demand
• Willingness to undertake any necessary training for the role

Please note that applications may be reviewed by both LMS and Imperial staff