Department of Biochemistry University of Oxford Department of Biochemistry
University of Oxford
South Parks Road
Oxford OX1 3QU

Tel: +44 (0)1865 613200
Fax: +44 (0)1865 613201
Image showing the global movement of lipids in a model planar membrane
Matthieu Chavent, Sansom lab
Anaphase bridges in fission yeast cells
Whitby lab
Lactose permease represented using bending cylinders in Bendix software
Caroline Dahl, Sansom lab
Epithelial cells in C. elegans showing a seam cell that failed to undergo cytokinesis
Serena Ding, Woollard lab
Collage of Drosophila third instar larva optic lobe
Lu Yang, Davis lab
First year Biochemistry students at a practical class
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Anthony Watts
Resolving structural details of membrane peptides and proteins at high resolution

Co-workers: Juan Bada Juarez, Juan Bolivar Gonzalez, Claudia Cassidy, Patricia Dijkman, Peter Fisher, Stephanie Gover, Alice Hart, Rosana Inácio dos Reis, Peter Judge, Steven Lavington, Juan Munoz-Garcia, Marc-Philipp Pfeil, Javier Vinals Camallonga, Daniel Yin, Soumia Zeghida.

How cells react to the external environment is still a major challenge in biology. Receptor and transporter proteins play pivotal roles in signalling and trafficking into and out of the cell. Smaller proteins and peptides can illicit dramatic changes in cellular behaviours, whether they are a signalling hormone, a component of an ion channel or induce structural changes such as cell death through lysis. We use a battery of biophysical methods to understand these processes in a quantitative way with a view to describing functional details that can ultimate lead to design of new therapies and infection control.

Cell signalling
 

The neurotensin receptor (NTS1 a class of GPCR), play a pivotal role in neurotransmission, particularly disease and is a marker for colon cancer. We have expressed the protein in E. coli in structural biology amounts in a functionally competent form for structural studies, some of which involve single molecule approaches for bionanotechnological and drug design applications.

NTS1 is now available highly purified monodispersed in detergent and in a ligand-binding form. One approach to monitoring ligand binding has been to develop a novel surface plasmon resonance (SPR)method for tagging the natural ligand, neurotensin (13-mer peptide), to the chip and monitoring protein binding. Fluorescently tagged NTS1 has also been used in fluorescence resonance energy transfer methods to resolve long range information of protein-protein, induced signalling.

Using quantitative approaches such as single molecule studies a SPR and novel MST (microscale thermophoresis), we have been able to make an initial suggestion for the “GPCRInteractome”, to which further information can be added as it is obtained for this signalling system that is central to all eukaryote signalling processes and prime target for drug discovery.


Kinetics of the GPCR interactome. Showing some of the initial genetic steps in the GPCR signalling pathway.
Dijkman P.M., Watts A (2015) Lipid modulation of early G protein-coupled receptor signalling events, Biochimica et Biophysica Acta (BBA) - Biomembranes, Volume 1848, Issue 11, Part A, Pages 2889–2897
Adamson, R. and Watts, A. (2014) Kinetics of the early events of GPCR signalling, FEBS Letts,Volume 588, Issue 24, Pages 4701–4707
 

Bacterial Resistance

In the animal kingdom, especially reptile and fish small peptides act as antimicrobial agents, protecting against infection in the outer skin. Exploiting these fascinating properties, is something we have been focussing on recently. In particular, a new way of punching a hole into bacterial membranes, has been discovered. In delivering such peptides, we are exploiting polymer-stabilized lipid nano discs, about 10 nm (1,000 millionth of a metre) in diameter – there LipodisqTM particles also have potential for drug delivery and provide a membrane environment for membrane proteins without the use of detergents.
 


 

Christmas Lecture 2015 - podcast

 

Publications - 2016

Publications - 2015 

 Publications - 2014

Publications - 2013

Publications - 2012

More Publications...

A Fascination with Vision - a video lecture for non-specialists

Research Images - drug and ligand binding






Figure 1: Substituted imidazo-pyridines are inhibitors of the gastric H+/K+-ATPase. By specific labelling of members of this drug family with NMR visible isotopes, we have been able to define the full conformation of the bound ligand, and suggest mechanism for inhibition from homology modelling with a related protein. (Kim, Watts & Watts, 2005, J. Med. Chem. 48, 7145-7152 and Watts, 2005, Nature Reviews Drug Discovery, 4, 555-568; Williamson et al., 2007, PNAS, 104, 18031-18036)


Figure 2: The cation-π interaction of acetyl choline, a major brain neurotransmitter, and the ligand gated, nicotinic acetyl choline receptor has been resolved using solid state NMR, giving an insight into the binding mechanism and the residues surrounding the site. (Watts, 2005, Nature Reviews Drug Discovery, 4, 555-568; Williamson et al., 2007, PNAS, 104, 18031-18036)

Figure 3: The way in which retinal is restrained within its binding site in membrane-embedded mammalian rhodopsin, and the structural details of the site, have been resolved for the early activation states of this light-activated GPCR, using high resolution solid state NMR to measure atomic distances within the retinal to high accuracy (+/- 0.2Å). (Spooner, et al., 2004, J. Mol. Biol., 343, 719-730)


Contact:anthony.watts@bioch.ox.ac.uk
Graduate Student and Postdoctoral Positions: Enquiries with CV welcome
Website: www.bioch.ox.ac.uk/~oubsu