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.

CURIOSITY, CREATIVITY AND INNOVATIVE SCIENCE FOR DRUG DISCOVERY                                                                                                            

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Astex’s Molecular Sciences Group has multiple, permanent and 3-year fixed-term contract opportunities for skilled and motivated protein scientists and structural biologists (cryo-EM scientists and X-ray crystallographers).  The Molecular Sciences Group is responsible for supporting all activities from ‘gene to structure’ and for enabling Pyramid^TM, Astex’s fragment-based screening platform.  Disciplines encompassed within Molecular Sciences Group include recombinant protein production, X-ray crystallography, electron cryo-microscopy (cryo-EM) and biophysics (nuclear magnetic resonance (NMR), surface plasmon resonance (SPR), mass spectrometry (MS), isothermal titration calorimetry (ITC) and thermal shift assay/differential scanning fluorimetry (TSA/DSF)).

The roles are laboratory based and the successful candidates will be engaged in enabling targets for Pyramid^TM and supporting projects during all phases of the drug discovery process. You will be expected to work on diverse structural systems, but experience of working with integral membrane proteins and/or multi-protein complexes would be highly desirable. You will be required to work closely with protein scientists, structural biologists and biophysicists, as well as chemists, biologists, bioinformaticians and computational modellers as part of dynamic inter-disciplinary project teams. Applicants should have excellent verbal and written communication skills, be highly organised and have a proven ability to work in teams. Additionally, you will be able to pursue your personal development through internal and external presentations, collaborations, and publications in high impact journals.

When applying, please ensure you quote the reference number for the role you are applying for in your cover letter.
 

Protein Scientist (Ref: PS/0924)

The Molecular Sciences Group has well equipped protein science laboratories including eukaryotic and prokaryotic cell culture and harvesting facilities, a large fleet of dedicated chromatographic purification systems (AKTAs) and high throughput expression testing and protein purification capabilities. The group also encompasses extensive biophysics and protein characterisation expertise. The team is responsible for supplying recombinant protein to enable all aspects of Pyramid^TM campaigns, which utilise X-ray crystallography, cryo-EM and multiple orthogonal biophysical methods. You will be expected to operate in highly inter-disciplinary project teams and work on diverse protein target classes including integral membrane proteins, multi-protein complexes, protein-DNA complexes and small, soluble, proteins. Your primary remit will be to enable robust expression and purification protocols for challenging protein targets, with the aim of supplying high purity, homogeneous recombinant protein samples for structural biology (cryo-EM & X-ray), biophysics and bioassay studies. Beyond engagement with Astex’s project teams, you will also be expected to interact with external collaborators and contract research organisations.

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 Pyramid^TM 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

Protein X-ray Crystallographer (Ref: PXC/0924)

Astex has a state-of-the-art in-house X-ray crystallography facility including a Rigaku FRX X-ray source equipped with HyPix-Arc 150 and Eiger 1M detectors, Cobra cryo-streams and an ACTOR sample changer.  Crystallisation hardware includes two automated Formulatrix Rock Imagers and Hamilton StarLet, Integra Viaflo96, Mosquito and sciFLEXARRAYER liquid handling systems. High throughput crystallographic fragment screening continues to be integral to Astex’s Pyramid^TM platform and Astex has routine access to beam-time at UK and European synchrotron radiation sources, as well as extensive in-house computing facilities. Astex has developed proprietary structure generation pipelines that are fully database integrated and has a proven track record of innovating in the protein crystallography space. Working within highly inter-disciplinary project teams, your primary remit will be to enable and support Pyramid^TM campaigns and to provide structural biology support for later stage drug discovery programs.

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

Why Astex

We offer excellent training and career development opportunities as well as highly competitive salary and benefits package including hybrid working options to promote a flexible and inclusive work environment.

At Astex we embrace diversity and equality of opportunity. We are committed to building an inclusive and diverse Company representing all backgrounds, harnessing industry-leading scientific innovation and behaviours.

Astex is situated 2.5 miles from Cambridge City centre on the Cambridge Science Park. The Park has onsite sports facilities and excellent transport links to London.

More information

For information on Astex Pharmaceuticals please visit: www.astx.com
For information on Otsuka Pharmaceuticals please visit: www.otsuka.co.jp