Structural Biology Opportunities

at  Astex Pharmaceuticals

Astex Pharmaceuticals is a world leader in innovative drug discovery and development. The company has successfully applied its proprietary Fragment-Based Drug Discovery platform to generate multiple new drug candidates that are progressing in clinical development. Successful collaborations have led to three launched oncology drugs (Kisqali® partnered with Novartis, Balversa® partnered with Janssen and Truqap™ partnered with AstraZeneca). Astex continues to grow and focuses on Neurological Disorders and Oncology.

ESSENTIAL SKILLS & EXPERIENCE

• Ph.D. with post-doctoral, or equivalent experience
• Extensive experience in recombinant protein expression in prokaryotic and eukaryotic systems
• Proficiency in chromatographic techniques (e.g. affinity, ion exchange, size exclusion)
• A proven track record of generating integral membrane proteins and multi-protein complexes for structural and biophysical studies
• Expertise in characterisation of proteins to ensure suitability for cryo-EM and other biophysical methods
• Excellent communication and team working skills

DESIRABLE SKILLS & EXPERIENCE

• Experience working with alternative membrane mimetics, such as nanodiscs, amphipols and liposomes
• Proven practical expertise with at least one of the following techniques: cryo-EM, X-ray crystallography, NMR, SPR, ITC, MS or TSA/DSF
• Experience with high-throughput protein expression
• Familiarity with FBDD and SBDD
  Cryo-EM Scientist (Ref: EMS/0924)
  Astex has established a state-of-the-art, in-house, cryo-EM facility, including two Glacios and one Krios transmission electron microscopes, a fully equipped cryo-EM sample preparation laboratory and extensive computing infrastructure. We have also developed custom data collection and processing workflows to facilitate the rapid generation and interpretation of cryo-EM structures for Structure- and Fragment- Based Drug Discovery (SBDD & FBDD). Astex accesses additional microscope time through membership of the Cambridge Cryo-EM consortium and by utilising dedicated fee-for-service cryo-EM facilities. Our commitment to the continued development of the cryo-EM platform means we now have an opening for a talented cryo-EM practitioner to join the Molecular Sciences Group. You will be expected to work in highly inter-disciplinary project teams and your primary remit will be to enable diverse cryo-EM structural systems for PyramidTM and beyond. You will also be expected to work closely with structural bioinformaticians and software developers within the Molecular Sciences and the Computational Chemistry and Informatics groups to help support the on-going development of Astex’s proprietary structural biology pipeline.
  Candidates should hold a PhD in single particle analysis using cryo-EM, or equivalent experience, and have proven post-doctoral experience working on multiple cryo-EM compatible structural biology systems.

ESSENTIAL SKILLS & EXPERIENCE

• Ph.D. involving the extensive use of cryo-EM
• Performing single particle cryo-EM including grid preparation and optimisation of samples for high resolution structure determination on a range of targets
• Processing of single particle cryo-EM data and familiarity with cryo-EM software packages
• Independent microscope user capable of setup, alignment and operation of microscopes, along with optimisation of data acquisition parameters
• Excellent communication and team working skills

DESIRABLE SKILLS & EXPERIENCE

• Experience in working with challenging protein targets, including membrane proteins and/or protein complexes
• Experience of X-ray crystallography
• Proven practical expertise with at least one of the following techniques: cryo-EM, X-ray crystallography, NMR, SPR, ITC, MS or TSA/DSF
• Familiarity with FBDD and SBDD

ESSENTIAL SKILLS & EXPERIENCE

• PhD in structural biology, or a related field
• Extensive experience in protein X-ray crystallography, including initial crystallization and optimization (including the use of crystallization robots such as Mosquito), data collection, structure determination and refinement
• Experience with standard crystallographic software packages, such as CCP4, Phenix, XDS, Autoproc and Coot
• Demonstrated competency in recombinant protein expression and purification strategies (e.g. bacterial, insect, and/or mammalian cell lines) for structure determination
• Excellent communication and team working skills

DESIRABLE SKILLS & EXPERIENCE

• Experience in working with challenging protein targets, including membrane proteins and/or protein complexes
• Experience of cryo-EM
• Proven practical expertise with at least one of the following techniques: cryo-EM, X-ray crystallography, NMR, SPR, ITC, MS or TSA/DSF
• Familiarity with FBDD and SBDD