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The University of Southampton
Institute for Life Sciences

RSC, Leverhulme, Chemistry & IfLS Seminars Event

Time:
13:00 - 16:00
Date:
20 April 2015
Venue:
Room 2207 Life Sciences Building 85 Highfield Campus

For more information regarding this event, please email ifls@soton.ac.uk .

Event details

Please join us for two seminars on the Biological applications of NMR

13:00 - Prof Philip Kuchel "Membrane Transport in Cells: NMR studies"

Living cells are characterized by having selective permeability of their plasma membranes to water, and many solutes such as amino acids, sugars, and Na+, K+ and Cl-. Integral membrane proteins, many of which have structural folds that have been solved by x-ray crystallography and NMR spectroscopy, mediate the physical translocation. Measuring the kinetics of the reactions operating in situ is a challenging task, as it requires separate identification of the transported species inside and outside the cells in a suspension. A serendipitous finding, which we call the ‘split peak effect’, opened up the use of NMR spectroscopy to measure the kinetics of many transport reactions that occur even on the sub-second time scale, using elegant magnetization transfer analysis.
I will give a historical perspective on water transport measurements in red blood cells, and then describe methods and results of exchange reactions using a range of solutes with the NMR ‘split peak effect’. This will include our recent application of 13C-rapid dissolution dynamic nuclear polarization (that enhancers 13C detectability 10,000 fold) to study the rapid entry of 13C-urea into red blood cells. This NMR approach paves the way to studying the effects of medicinals on transport reactions in intact cells in suspensions, and potentially in vivo.

 

14:00 - Dr Phil Williamson "Investigations into cell signalling by NMR"

Communication between cells relies extensively on integral membrane proteins to recognise the presence of external stimuli including neurotransmitters and hormones and mediate the transfer of information across the plasma membrane to initiate an intracellular response. Due to their favourable location in a number of cell signalling pathways they represent a attractive target for the development of novel pharmaceuticals, with over 60% of currently marketed drugs acting on integral membrane proteins. Despite their clear pharmacology importance, our current understanding of how integral membrane proteins functional at the molecular level is still compromised by the challenges associated with obtaining high-resolution structural information. Over the last 25 years solid-state NMR has emerged as a powerful technique for probing the structure and function of integral membrane proteins within their native lipid bilayer. In this lecture I will describe how solid-state NMR has contributed to the structural characterisation and localisation of drugs within their binding sites on integral membrane proteins focussing on ligand gated and voltage gated ion channels, two key families of protein involved in neuronal signalling. In conjunction with recent progress in X-ray crystallographic analysis of integral membrane proteins, I will highlight how this is providing us with novel insights into the function and regulation of integral membrane proteins, key information for the rational development of drugs against these important pharmaceutical targets.

 

15:00 - Refreshments, served in the Level 7 Observatory, Life Sciences Building 85

 

***All welcome to attend***

Speaker information

Prof Philip Kuchel,Leverhulme Professor, University of Sydney,Philip Kuchel FAA is a Leverhulme Visiting Professor in the Department of Chemistry with Malcolm Levitt. He was here in 2014 for 3.5 months, and this is his second stint in Southampton. He is known for his work on applying NMR spectroscopy to cellular systems to probe their metabolism, membrane transport on the sub-second time scale, and the rates of diffusion of solutes, including proteins, inside cells. He was appointed to a Chair of Biochemistry at the University of Sydney in 1980 and in 2013 was made Emeritus Professor. He is the coordinating author of ‘Schaum’s Outline of Theory and Problems of Biochemistry’ McGraw-Hill, and coauthor of ‘Modelling Metabolism with Mathematica’ CRC Press. His 440 scientific papers include the first description of 1H spin-echo NMR spectroscopy used to monitor metabolism in cells, the discovery of the transmembrane ‘split peak effect’ that is used to measure rapid membrane transport, and the first observation of ‘diffusion-diffraction’ of water in a cellular system.

Dr Phil Williamson,Lecturer, and Principal Investigator (Structural biology and biological membranes)

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