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Phil Williams

Professor of Biophysics, Director of Research and Knowledge Exchange, Faculty of Science

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Biography

I graduated with a Bachelors of Pharmacy degree from the University of Nottingham 1988 and qualified as a Pharmacist in 1989, after which I returned to the University to undertake a PhD on "Computational Studies in Scanning Probe Microscopy" under the supervision of Martyn Davies, David Jackson and Saul Tendler. I undertook postdoctoral research in the School developing the biological applications of SPM, in particular AFM, with one focus on the analysis and compensation for tip-induced artifacts. I was appointed to a lectureship in the School in 1996. In 2000, I was awarded a five-year Advanced Research Fellowship from the Engineering and Physical Sciences Research Council during which time I was able to develop research links with Evan Evans working at the University of British Columbia in Vancouver developing the theoretical understanding of force-induced dissociation and protein unfolding experiments. I was promoted to Associate Professor and Reader in Theoretical Biophysics in 2003.

I was a member and last head of the Laboratory of Biophysics and Surface Analysis, a research division with the School. The LBSA had an international leading reputation and track record in scanning probe microscopy and surface chemical analysis of pharmaceuticals, polymers and biomaterials. The LBSA remain the only grouping to receive the GlaxoSmithKline International Achievement Award, given for "Internationally recognized work on drug delivery and new techniques for surface and interface analysis".

In 2004, at the age of 37, I was one of the youngest pharmacists ever to be made a Fellow of the Royal Pharmaceutical Society of Great Britain, made in recognition of "distinction in science related to pharmacy".

I was promoted to a personal chair in 2008 as Professor of Biophysics.

I have been involved with the formation of a number of University spin-out companies and I am the co-founder of a successful spin-out from the LBSA, Molecular Profiles Ltd (www.molprofiles.com) (now Juniper Pharmaceuticals) which was awarded the Queens Award for Enterprise in the category of Innovation in 2007 and 2011.

I am currently Director of Research and Knowledge Exchange in the School of Pharmacy.

Expertise Summary

My expertise is in the study and understanding of protein folding through single molecule experiments and computational simulation.

I am a Fellow of the Royal Pharmaceutical Society (FRPharmS)

I am a Fellow of the Royal Society of Chemistry (FRSC) and Chartered Chemist (CChem)

I am a Member of the Institute of Physics (MInstP)

Teaching Summary

I convene a 2nd year Masters of Pharmacy module on Sexual Health and Pregnancy (B32SHP). This module adopts the flipped classroom approach of "classwork at home, homework in class".

Research Summary

My current research centres on the biophysics of protein evolution, folding and function, and the development and application of biophysical and computational techniques to study them.

Protein Evolution

A simple analysis of the shape of proteins and of their constituent amino acids has revealed some remarkable features that point to how proteinaceous life has evolved. Our recent analysis of all the proteins deposited in the protein databank, for example, has enabled us to derive simple mathematical expressions that predict their behaviour in the cell, and thus point to why cells and proteins are the shape and size they are. As the properties we describe follow simple laws of physics, we can hypothesize that proteins and cells would evolve similarly in any environment and thus argue that if life has evolved elsewhere it would be similar to that on earth. Our current research is extending our ideas: If we can understand how amino acids are shaped to form proteins, understand how proteins are shaped to function in the cell, and how cells are sized to optimize function in an organ, can we predict what shape and size organs will be, and can we then predict the size and shape of multi-cellular life?

Protein Mechanics

Our new bioinformatic tools, developed to allow us to predict and compare the mechanical properties of proteins, add further to our studies of protein evolution. We are interested in how specific proteins have evolved their 'mechanical' role, be it structural, transduction, motor, etc. Being able to understand how these properties has evolved will enable us to better understand how mutations may affect them and give rise to pathogenic disease. Specific interests include the proteins participating in blood haemostasis (von Willebrand Factor, for example) and proteins of muscle to understand the effect of disease (dystrophies), aging, and altered environment (supine posture, extended space-flight).

Protein Aggregation

Many diseases arise from protein misfolding and protein unfolding followed by aggregation. Using single molecule force experiments (atomic force microscope, biomembrane force probe, optical tweezers) we are investigation how disease can arise at the level of the single protein. Current research in this area includes understanding and controlling cataract formation.

Biophysical Techniques

The tools we develop and apply to understand protein structure and function have wider application, and we are applying them to understand the biophysics in many projects across the School. These include, for example, the understanding of micro and nanoparticle formation in microfluidic and nanoprecipitation devices using the micro-pipette aspiration of the BFP, understanding cell adhesion to structured biomaterials using the AFM, BFP and OT, development of fragment screening approaches at the single molecule level, and understanding and modifying cell adhesion in models of metastatic cancer.

Selected Publications

Past Research

I developed new methodologies that permit single molecules to be manipulated and the forces that hold them together to be measured. To complement these studies, I also developed both the necessary theoretical understanding of the behaviour of molecules and novel computational tools to model these experimental investigations. Such measurements on single molecules opened up new avenues to study normal and aberrant biological processes that are important therapeutic targets in biology and medicine. My work in these areas of theory, computation, and bio-nanotechnology is exemplified by:

• Development of the theoretical understanding of molecular interactions and how nature tailors energy potentials for biological function. Part of this work was undertaken with Dr Clarke, Cambridge, and Prof. Lindsay, Arizona. • Research in bio-nanotechnologies, such as the UK's only biomembrane force probe, and experimental methodologies to measure biological systems and processes. Part of this work was undertaken with Dr Emsley, Prof. Jensen (School of Mathematics), Prof. Lane, Imperial, and Prof. Evans, British Columbia. • Derivation and application of computational methodologies to predict and interpret measurements of biological processes. Part of this work was undertaken with Prof. Elber, Cornell.

I have supervised research students from the Department of Chemistry, University of Cambridge and Department of Physics, University of Genoa, in my laboratories. I have used funds from my EPSRC Advanced Research Fellowship to enable my students to work in the laboratories of Evan Evans at the University of British Columbia, Vancouver and at Boston University, of Stuart Lindsay at the Department of Physics and BioDesign Institute, Arizona State University, and of Ron Elber, Department of Computer Science, Cornell. I have published over 150 research papers and book chapters.

Students recently obtained their PhDs from my group have gone on to undertake postdoctoral work with world-leading protein folding groups (Seattle) and tissue engineering and molecular biology groups (Hawaii).

Future Research

One area of future work that is being designed at the moment is to study links of mechanical properties between genotype and phenotype. This work will allow relationships between the mechanical properties of molecules and the effect of mutation with changes in function of the organism/organ in which the protein is expressed, thus giving a unique biophysical insight to the dystrophic disease, aging, and how life has evolved in the 1G environment of the earth.

School of Pharmacy

University of Nottingham
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Nottingham, NG7 2RD

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