Sir Peter Mansfield Imaging Centre

Title: DNP-enhanced NMR studies of cellular membrane disruption induced by Abeta40 peptides.

Supervisor: Alexey Potapov

Summary

Magnetic resonance spectroscopy is very powerful tool, allowing to study fine details of biomolecular structure and construct high-resolution structural models of biomolecules. In particular, we use and develop our own new techniques of magnetic resonance such as pulsed electron paramagnetic resonance (EPR) and solid state nuclear magnetic resonance (NMR) for reporting on fine details of biomolecular structure.

Aggregates of amyloid-beta peptides have been implicated as causative agents in Alzheimer's disease, however their structures and their exact toxic mechanism, in other words, how they disrupt a cell membrane, is not well understood yet. We study the structures of amyloid-beta peptide aggregates and their interaction with cell membrane using modern tools of magnetic resonance spectroscopy and other biophysical methods.

To that end, we use a novel technique for enhancement of NMR signals called the Dynamic Nuclear Polarization. The boosted signals allow us to study species that are present in small amounts, and are impossible to study using other methods.

We are looking for a motivated PhD candidate interested in biophysical applications of magnetic resonance spectroscopy. This position is suitable for students with background in Physics, Chemistry or other related fields.

Aggregates of amyloid-beta peptides have been proposed to play role in causing Alzheimer's disease, however, their mechanism of action is not clearly understood. In this project, carried out in collaboration with SUNY Binghamton (USA), we focus on the process of cell membrane disruption by amyloid-beta and study its details using advanced nuclear magnetic resonance (NMR) techniques. One of such techniques is the dynamic nuclear polarization (DNP) allowing the NMR signals to be increased by a large factor. University of Nottingham is hosting a modern DNP-enhanced solid-state NMR Facility (unique in the UK) funded by a grant of £2.5 M from EPSRC.

The PhD studentship is available immediately, and is fully funded for 3.5 years via a stipend covering PhD tuition fees (at the Home/EU rate) and a tax-free living allowance.

For more details please contact Dr Alexey Potapov (alexey.potapov@nottingham.ac.uk)