Dr Neil Thomson

Dr. Neil Thomson is a Reader in Biological Physics and Bionanotechnology with a joint position between the Department of Oral Biology in the Leeds Dental Institute and the School of Physics and Astronomy. He held an EPSRC advanced research fellowship in the Department of Physics and Astronomy, University of Leeds from April 2000 to March 2005. He was then employed as a Leeds University Research Fellow from April 2005 to Sept. 2007. He obtained his B.Sc. and Ph.D. in Physics from Bristol University in 1990 and 1994, respectively. He joined the Molecular and Nanoscale Physics Group, Leeds in March 2000, after postdoctoral positions at: Physics Dept., University of California Santa Barbara, USA (1995-1997) and the School of Pharmacy, University of Nottingham (1998) and the Departement de Physique, Ecole Polytechnique Federale de Lausanne, Switzerland (1999).

Research Areas: Biological Physics, Bionanotechnology, Atomic Force Microscopy (AFM)

Research Projects and Collaborations

My research concentrates on the development and use of atomic force microscopy to study the structure and dynamics of biological systems, particularly down to the molecular level. All my work is collaborative The structure and mechanism of action of E. coli DNA gyrase and other topoisomerases is being probed using AFM. Gyrase is a member of the protein family, topoisomerases, which are responsible for controlling the topology (supercoiling and knotting) of DNA. It is a molecular motor, which uses the energy released in ATP hydrolysis to relax positive supercoils, or introduce negative supercoils into double-stranded DNA. Since gyrase is instrumental in controlling bacterial gene expression, it is a desirable target for antibiotics. AFM imaging is determining the low-level resolution, tertiary structure of the enzyme and its’ relationship with DNA templates. Details of the proteins mechanistic action can be determined through static imaging of the protein in the presence of DNA and various drug molecules and analogs of ATP. A longer-term goal is to image DNA gyrase turnover in real-time within the microscope, as has been previously achieved in my postdoctoral work for E. coli RNA polymerase.

Protein-protein interactions

The structure and formation of amyloid fibrils of the protein 2-microglobulin (2m) has been characterized by AFM in conjunction with complementary biophysical and biochemical techniques. AFM is a particularly suitable tool for studying structures formed in heterogeneous aggregating protein solutions, which are unsuitable for ensemble measurements. Acidification of 2m induces amyloid formation in vitro and variations in environmental conditions produce different fibril morphologies. Aggregation pathways have been elucidated through imaging of the self-assembling species quenched at different time points. In the longer term, assembly can be followed in real-time in the AFM under a variety of biologically relevant conditions, as steps toward mimicking amyloidogenesis in vivo.

Recently, we have investigated the mechanical properties of amyloid-like fibrils and related fibrils using AFM to probe individual fibrils in a bending or extensional configuration. These bio-fibrils are typically about 10 nm in diameter and can be several tens or hundreds of microns long, which makes them suitable candidates for nanoscale structural elements in new materials, such as composites or networks. The aim is to test the homogeneity of mechanical response along and between fibrils with the ultimate goal of relating mechanical properties to structure. This research has been funded by the BBSRC and assesses the suitability of these biological structures as novel materials.

Bacterial Research

Molecular recognition mapping on oral bacterial cell surfaces

We are developing AFM methods to map specific sites on bacterial cell surfaces using the force signal in the AFM modulated via molecular recognition. In this approach, pioneered by Hinterdorfer’s group (Linz, Austria), the AFM tip is functionalized with a molecular or moiety (e.g. antibody or antibody fragment) that interacts specifically with molecules or molecular motifs present on the cell surface. The specific interaction will generate image contrast that should allow the localization of receptors down to the nanometre length scale. This research has previously been funded by an MRC studentship.

Cyanobacterial surface structure and motility studied by AFM

Knowledge of bacterial cell surface ultrastructure is based largely on the observation of dead cells and we therefore have no idea of the true nature of the surface in live cells. The development of atomic force microscopy (AFM) has provided the opportunity to study, for the first time, the surface of living bacteria. We were the first group in the world to recently succeed in immobilising filamentous, motile cyanobacteria and scanning the living cells under liquid. This project is employing AFM scanning to a range of live cyanobacteria, immobilised under liquid, to visualise the topography of the cell surface and the functioning of the molecular motors that drive gliding motility. Additionallly, changes in surface properties during physiological and developmental changes in the bacteria are under study. This project has been funded by the Leverhulme Trust and the EPRSC Doctoral Training Centre at the physical-life science interface.