Protein Engineering by Phenotypic Screening in Microfluidic Droplets

A graduate studentship leading to the award of a PhD is available from 1 October 2015 (or later) to work at Cambridge University in the Biochemistry Department (with Dr. F. Hollfelder -http://www.bioc.cam.ac.uk/hollfelder) and at MedImmune (with Dr. R. Minter -http://www.medimmune.com/).

Antibodies are usually raised against purified proteins, e.g. by affinity panning. In many cases this approach has led to valuable therapeutics, but good binders can also be therapeutically inactive, if the binding event is not linked to a biological effect. In a radical departure from conventional antibody screening, we will co-compartmentalise one antibody species with a single cell in pico- to nanolitre droplets that are generated at high speed (> >1kHz) in microfluidic devices. In this way we can screen millions of clones for their ability to alter cellular behaviour. Such an approach will be uniquely valuable to raise therapeutic molecules against targets that are relatively unstable, difficult to handle or cannot be produced in vitro, so that affinity panning is not an option. In the course of the studentship this new technology will be developed and applied and validated by addressing currently undruggable targets.

Candidates will be mainly based in the Biochemistry Department (in central Cambridge), but also work for extended secondments at MedImmune's Granta Park Site (near Cambridge) and/or in their US headquarters (Gaithersburg, Maryland) and thus receive training in a basic science as well as an industrial context. 

Applicants should have a first or upper second class degree in biochemistry, biotechnology, chemistry or a related, relevant subject. Specific skills in protein engineering, directed evolution, cloning, DNA manipulation (including preparation and handling of DNA libraries) and familiarity with other molecular biology techniques (e.g. phage or ribosome display) are advantages.

This project is fully funded by the BBSRC (via a CASE award) for up to 48 months.  Studentships are only available to citizens of the EU or the European Economic Area. To qualify for the full rate of the studentship UK residency requirements must be met (see e.g.

http://www.mrc.ac.uk/Fundingopportunities/Applicanthandbook/Studentships/Eligibility/index.htm#P17_968or http://www.bbsrc.ac.uk/web/FILES/Guidelines/studentship_eligibility.pdf). 

The full stipend will be paid at RCUK rates for the 4 year duration.

Fixed-term: The funds for this post are available for 4 years in the first instance.

Applications should contain a description of your research interests (e.g. as part of the cover letter) and your detailed CV (with exam marks and all relevant practical experience). Please also include the names and email-addresses of at least two referees, who know you from your courses or laboratory research work. Send your application by 15 February 2015 by email to fh111<στο>cam.ac.uk. 

Informal inquiries can be made by contacting Dr Florian Hollfelder - fh111<στο>cam.ac.uk

Please quote reference PH05109 on your application and in any correspondence about this vacancy.

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