Research Technician in London

London Full-Time On-site

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Description

Research Technician – Cryo-EM / Structural Biology LMS 2961
£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/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 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

Additional information:

Applicants should submit a CV, names and contacts of two scientific references along with a cover letter stating why you are applying for this role (providing evidence against the requirements of the job as per the job description and person specification). Applications without a cover letter will not be accepted. Please quote reference number LMS 2961.

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