Postdoctoral Training Fellow - X-ray crystallography

About you

 Applicants must have a PhD (or equivalent) in a biological or physical science, with demonstrable experience in X-ray crystallography and protein biochemistry. Experience in cryo-EM specimen preparation and data processing would be an advantage, though not strictly mandatory. Experience in molecular biology, protein expression and purification, as well as biophysical characterisation of protein samples would also be highly desirable.

Department/Directorate Information

Department/Directorate Information:

The Hit Discovery and Structural Design Team uses biochemical and biophysical assays to perform small-molecule high-throughput screening and fragment-based hit discovery, coupled with X-ray crystallography and cryo electron microscopy to enable structure-based drug design within the CCDD. These methodologies are underpinned by state-of-the-art protein expression, purification and biophysical characterisation capabilities, allowing for the generation of large quantities of high-quality protein targets.

Pertinent to this role, the team’s protein production laboratories are equipped with six state-of-the-art GE Healthcare Akta Pures for protein purification and has the capabilities to produce recombinant proteins in bacteria, insect cells and mammalian cells. The team is also equipped with a broad range of biophysical technologies including SPR (GE Healthcare T200 & 8K Biacores), ITC (Malvern MicroCal iTC200), DSF/TSA (Nanotemper Prometheus & Biorad 384-well thermal cyclers) and DLS (Xtal concepts SpectroLight600). Additionally, we have access to Mass Spectrometry and NMR facilities within the division, used both for sample QC and assays (MS-based assays, ligand- and protein-observed NMR). Our screening laboratory is equipped with a number of HTS multimode plate readers (including two BMG Pherastars) for biochemical/functional target protein characterisation and compound testing. To enable fast and accurate assay preparation, the team possesses a broad range of liquid handling equipment, including pipetting robots and two Beckman ECHOs acoustic dispensing machines integrated onto Access systems for compound dispensing. The team hosts a state-of-the-art crystallisation laboratory, equipped with specialised liquid handling robots (SPT Labtech Mosquito and Dragonfly), coupled with a plate imaging robot (Formulatrix RockImager 1000) to enable fast discovery and optimisation of crystallisation conditions. We also possess a rotating anode X-ray source onsite in Sutton (Rigaku FRX with Pilatus 300K detector) and benefit from very good access to Diamond Synchrotron at the Harwell Science and Innovation campus, Didcot, UK. Finally, the team has access to the cryoEM facilities of the Division of Structural Biology. These include an in-house Glacios and 30% direct access to a Titan KRIOS located at the Francis Crick Institute. Both microscopes are equipped with Falcon III detectors and volta phase plates (VPP).

You will be joining a team working at the crossroads of the drug discovery activities of the Centre for Cancer Drug Discovery, where scientific excellence and team science are core values. You will be working in close collaboration with colleagues in the fields of biology, chemistry, biochemistry, biophysics, structural biology, DMPK and computational chemistry. This position will also offer training in new techniques and support will be available for attending training courses and appropriate academic meetings.