PhD Research Project

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Exploring the role of solvent in global protein dynamics

Institution:

University of Leeds

Dept/School/Faculty:

Faculty of Biological Sciences

PhD Supervisor:

Dr A Pearson

Application Deadline:

No more applications being accepted

Funding Availability:

Competition Funded PhD Project (European/UK Students Only)

PhD Research Project

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Protein dynamics are fundamental to their function as catalysts and molecular machines. However, our understanding remains limited, in part by a lack of experimental methods able to provide both high temporal and spatial resolution information. NMR is such a technique but requires complex isotopic labeling and is not suitable for large macromolecular complexes. To meet this need, we are developing a suite of methods (time-resolved X-ray crystallography and THz spectroscopy) to probe the global and local dynamics of both molecular and macromolecular systems. Our work, and that of others in this area, has already indicated that there are considerable differences between molecular and macromolecular systems that limit, in particular, the resolution of the information that can be obtained from macromolecular systems. These include the diffraction quality of crystals, the time and frequency resolution of the THz response and sensitivity to radiation damage.
Our hypothesis is that a major determinant of these differences is the presence of solvent, both the hydration shell and the bulk solvent phase.
This project will investigate the role of water in peptide and protein dynamics. Specifically we aim to (a) identify the length at which a polypeptide ceases to behave like a small molecule and begins to manifest macromolecular behavior, (b) the amount of water which is needed for biological activity, (c) the size of the ordered hydration shell around a polypeptide and (d) the point at which solvent begins to behave as bulk water (and whether this correlates to (b)). We will address these questions using a combination of X-ray crystallography, THz spectroscopy and simulation. Considerable work in this area has already been carried out in the neutron scattering field and, where data is not already available, we will carry out complementary neutron scattering studies to compare with the THz results.

Funding Notes:

EU candidates must have been resident in the UK for a minimum of 3 years.
The studentship will provide fees and stipend (£13,590 for 2012-13) for 3.5 years.
Applicants should have a 2.1 or above at undergraduate level. Please include CV and transcripts with your application (link below).

To apply please go to: https://studentservices.leeds.ac.uk/pls/banprod/bwskalog_uol.P_DispLoginNon