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
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:
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:
Desirable:
Knowledge and experience (will be assessed from application form and at interview):
Essential:
Personal Skills / Behaviours / Qualities (will be assessed at the interview):
Essential:
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
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Online applications only preferred for this role. Please submit a CV and covering letter which clearly outlines how you fulfil the criteria specified along with your motivation for UKRI and the role. Ensure that the job reference number is included in the filename description of each document uploaded. Note that failure to address the above criteria or submit an application without a covering letter may result in the application not being considered.
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