Research Technician

Description

Research Technician Cryo-EM / Structural Biology LMS
2961
37476 - 39470 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 LMSImperial 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)
• E…