BA Hons., MA, Biochemistry Department, University of Oxford (1991/1995); D.Phil in Biochemistry, Biochemistry Department, University of Oxford (1995/2000); Post-doctoral Fellow, ETH-Zurich, Switzerland (2000/2005); Charge de Recherche, CNRS / ULP-Strasbourg (2005/2007); Wellcome Trust, Research Career Development Fellow, University of Southampton (2007-).

Molecular interactions in biological membranes
Biological membranes are ubiquitous in nature and play a vital role in defining the interface of the cell with its environment and its intracellular compartmentalisation. In order to facilitate the transfer of information and materials across these barriers cells have evolved families of integral membrane proteins. The goal of our research is to understand the function of these proteins in their native lipid environment and for this purpose; we are developing solid-state NMR techniques which enable us to probe the structure and dynamics of these systems at an atomic level. In conjunction with other biophysical techniques, this method allows us to characterise how membrane proteins interact with other proteins, the surrounding lipids and other small molecules and to determine how these interactions modulate their function.

Regulation of protein trafficking
The targeting of integral membrane proteins to the appropriate organelle or region at cell surface is vital to their function in eukaryotic cells. It is proposed that interactions between lipids and integral membrane proteins may play an important role in regulating this targeting process. Exploiting the potential of solid-state NMR techniques to study the structure of integral membrane proteins under near physiological conditions, we hope to be able to determine how bilayer composition and lateral phase separation may regulate the structure, oligomeric state and localization of integral membrane proteins and determine the role that this may play in regulating intracellular protein trafficking. These studies may provide molecular insights into a range of diseases linked to the mistrafficking of proteins.

Amyloidogenic diseases
A number of diseases important to modern society including Alzheimer’s, Parkinson’s and Huntington’s are characterised by the deposition of proteins as insoluble aggregates within the body. Solid-state NMR provides us with a unique opportunity to probe the structure of these aggregates at a molecular level. Currently we are employing solid-state NMR in conjunction with other biophysical techniques to characterise the structural transitions that result in the formation of these deposits. These studies are providing us with valuable insights into the onset and progression of these diseases and ascertaining the role other in-vivo factors may play in these diseases.

Selected Publications:

Williamson, P.T.F. (2009) Solid-state NMR for the analysis of high-affinity ligand/receptor interactions, Concepts in Magnetic Resonance 34A, 144-172

Marenchino, M., Williamson, P. T., Murri, S., Zandomeneghi, G., Wunderli-Allenspach, H., Meier, B. H., and Kramer, S. D. (2008) Dynamics and Cleavability at the alpha-cleavage site of APP(684-726) in different lipid environments, Biophysical Journal J95, 1460-1473.

Williamson, P. T., Verhoeven, A., Miller, K. W., Meier, B. H., and Watts, A. (2007) The conformation of acetylcholine at its target site in the membrane-embedded nicotinic acetylcholine receptor, Proc Natl Acad Sci U S A104, 18031-18036.

Chandrasekhar, W.F. van Gunsteren, G. Zandomeneghi, P.T.F. Williamson, B.H. Meier. Orientation and conformational preference of leucine-enkephalin at the surface of hydrated dimyristoylphosphatidylcholine bilayers. Journal of the American Chemical Society 2006 (128) 159-170

P.T.F. Williamson, G. Zandomeneghi, F.J. Barrantes, A.Watts, B.H. Meier. Structural and Dynamic Study of the γ-M4 transmembrane domain of the nicotinic acetylcholine receptor in lipid bicelles. Molecular Membrane Biology 2005 (22) 485-496

F. Lindstrom, P.T.F. Williamson, G. Gröbner. Molecular insights into the electrostatic membrane surface potential by 14N/31P MAS NMR. Journal of the American Chemical Society 2005 (127) 6610-6616

P.T.F. Williamson, B.H. Meier, A.Watts. Solid State NMR studies of the nicotinic acetylcholine receptor. European Biohysical Journal 2004 (33) 247-254

P.T.F. Williamson, A. Verhoven, M .Ernst, B.H. Meier. Determination of homonuclear dipolar couplings in multispin systems. Journal of the American Chemical Society 2003 (125) 2718-2722

G. Zandomeneghi, P.T.F. Williamson, A. Hunkeler, B.H. Meier. Switched angle spinning applied to bicelles containing phospholipid associated peptides. J. Biomolecular NMR 2003 (25) 125-132

P.T.F. Williamson, S.K. Bains, C. Chung, R. Cooke & A. Watts. Characterisation of the interactions of NT(8-13) with the G-protein coupled neurotensin receptor: a solid state NMR approach. FEBS Letters 2002 (518) 111-115

P.T.F. Williamson, J.A.Watts, G.H. Addona, K.W. Miller & A.Watts. Dynamics and orientation of N+(CD3)3-bromoacetylcholine bound to its binding site on the nicotinic acetylcholine receptor. PNAS 2001 (98) 2346-2351

P.T.F. Williamson, J.F. Roth, T. Haddingham & A. Watts. Expression and Purification of Recombinant Neurotensin in Escherichia coli. Protein Expression and Purification 2000 (19) 271-275

Watts, I.J. Burnett, C. Glaubitz, G. Gröbner, D.A. Middleton, P.J.R. Spooner, J.A. Watts & P.T.F. Williamson. Membrane protein structure determination by solid state NMR. Natural Product Reports 1999 (16) 419-423

P.T.F. Williamson, G. Gröbner, P.J.R. Spooner, K.W. Miller, A. Watts. Probing the agonist binding pocket in the nicotinic acetylcholine receptor: A high-resolution solid-state NMR approach. Biochemistry 1998 (37) 10854-10859

Selected book chapters and reviews

P.T.F. Williamson, M.Ernst & B.H. Meier. MAS Solid state NMR of isotopically enriched biological samples. In Bio-NMR in drug research, edited by O. Zerbe (Wiley-VCH)

P.T.F. Williamson, S.K. Bains, C. Chung, R. Cooke, B.H. Meier & A. Watts. Characterisation and assignment of uniformly labelled NT(8-13) at the agonist binding site of the G-protein coupled neurotensin receptor. S.R. Kiihne and H.J.M de Groot (eds.), Frontiers in structural biology (2001) Kluwer Publishers, Dordrecht, The Netherlands. 215-226

Watts, I.J. Burnett, C. Glaubitz, G. Gröbner, D.A. Middleton, P.J.R. Spooner, J.A. Watts & P.T.F. Williamson. Membrane protein structure determination by solid state NMR. Natural Product Reports 1999 (16) 419-423