PhD position at the University of Edinburgh, UK

Call for applications: EASTBIO DTP PhD studentship: "Targeting transient protein states for the design of chemical probes of Cyclophilins function"

Supervisors: Dr Julien Michel, Prof Alison Hulme, School of Chemistry, and Prof Malcolm Walkinshaw, School of Biological Sciences, University of Edinburgh.

We are looking for outstanding students with a passion for research at
the interface of chemistry and biology for a fully funded 4-year
EASTBIO PhD studentship (fees and stipend at the standard rate). The
project is available from September 2018 for candidates that satisfy
BBSRC studentship eligibility requirements (see if you are unsure). The main
objective of this PhD project is to contribute to the development of
novel chemical probes of Cyclophilins function using a range of
state-of the art methodologies from chemical, structural and
computational biology. Inhibition of diverse Cyclophilin isoforms
could pave the way for novel therapeutic treatments in
immunosuppression, neuroprotection/degeneration or viral diseases. Yet
drug development efforts have been limited historically due to the
challenge of selectively inhibiting a given Cyclophilin isoform.

Our laboratories have a long-standing interest in the use of
biophysical, chemical, and computational methods to discover novel
Cyclophilin ligands. In this PhD project you will build on our
previous and current body of work and pursue Cyclophilin inhibition by
exploiting protein dynamics to reveal ‘transient protein states’ that
are not apparent in structures readily solved by X-ray crystallography
experiments. We have developed a methodology to detect such transient
protein states via an integrative structural biology approach that
combines X-ray crystallography and protein NMR measurements with
molecular dynamics simulations to deliver dynamical models of
Cyclophilins. Models analysis informs the rational design of small
molecules to selectively bind and stabilize such transient states.
Such small molecules are selected from existing libraries, or
synthesized and assayed for binding and functional behaviour using NMR
and isothermal titration calorimetry experiments. Through targeting a
transient protein state that is unique to a given Cyclophilin isoform,
you will identify small molecules with high sub-type selectivity.

The ideal applicant will have a strong academic record, a BSc or
MChem/MSc degree in Chemistry, Biochemistry or related fields, and
previous research experience in structural, chemical or computational
biology. The ideal candidate will also demonstrate keen interest in
molecular recognition, enthusiasm for multidisciplinary research, and
a passion for improving human health with small-molecules.

To apply, please send initially a cover letter and CV to Informal enquiries are encouraged as soon as
possible. Shortlisted candidates will be invited to apply formally to
the EASTBIO DTP. Candidates should make initial contact by December
1st 2017 at the latest. Late applications may not be considered.

For further information please visit:

Dr. Julien Michel,
Royal Society University Research Fellow
Room 263, School of Chemistry
Joseph Black Building, University of Edinburgh
David Brewster Road
United Kingdom
phone: +44 (0)131 650 4797