Our research employs approaches from the following fields

• Structural biology
• Physical biochemistry
• Synthetic biology
• Molecular biology
• Molecular enzymology

7 glycoside hydrolase (GH) enzyme

Professor John McGeehan solved the X-ray crystal structure of a novel family 7 glycoside hydrolase (GH) enzyme. Biophysical and biochemical data show that this enzyme is highly salt tolerant with novel features that make it attractive from an industrial biofuels perspective.

Novel approaches to targeting antibiotic resistance

With antibiotic resistance on the rise, research into understanding the workings of bacterial organisms is crucially important, as are new approaches to combating the infections they cause. Professor Callaghan and Dr Gowers, together with colleagues at the University of Leeds, Imperial College London, the University of Viscosa and DSTL, are working to address this topical and strategically relevant issue. A range of approaches are being explored; from targeting essential enzymes found in pathogenic bacteria, to targeting molecular switches responsible for turning on bacteria virulence.

PETase enzyme

Professor McGeehan and researchers at the U.S. Department of Energy's National Renewable Energy Laboratory and the University of South Florida, solved the high-resolution structure of the PETase enzyme using X-ray crystallography at the Diamond Light Source. The team used the structure to design an improved version of the enzyme, making it more efficient, and raising the possibility of further efficiency gains.

Structure-function relationships in matrix metalloproteinases 

Dr Pickford's group are investigating the molecular mechanisms that underpin the breakdown of collagen fibres in the articular cartilage that lines the synovial joints of the body. The gradual destruction of this tissue is a common pathological feature of the chronic inflammatory condition rheumatoid arthritis (RA). The enzymes predominantly responsible for breaking down collagen in RA are members of the matrix metalloproteinase (MMP) family. These collagen-degrading MMP enzymes are secreted by cells as inactive zymogens which are then activated in the extracellular space. The Pickford group are researching the mechanism of activation of these collagenases and the way in which they break down articular collagen.

Studying and exploiting RNA-based interactions

Professor Callaghan’s team researches RNA-based control mechanisms important in gene expression pathways. To explore the molecular interactions involved, she developed an innovative technology to support high-throughput studies and, with Dr Pickford and colleagues at the Universities of Oxford and Surrey, has completed proof-of-concept studies. Together with Dr Scarlett and colleagues at the University of Massachusetts, applications within the synthetic biology domain are presently being explored, whilst it’s utility within the RNA therapeutics field is being explored with commercial partners. The technology is the subject of a patent.

Professor Geoff Kneale
 

Sadly, our friend and colleague Professor Geoff Kneale passed away suddenly on 24 June. Professor Kneale, GGK to the many people who passed through his laboratory over the years, was a driving force behind Biophysics teaching and research at Portsmouth for over 30 years. Geoff obtained his undergraduate degree in Biophysics from the University of Leeds and completed a PhD in small molecule crystallography, also at the highly respected Leeds Biophysics laboratories in 1975.

After his PhD Geoff took up a post-doctoral position within the Biophysics group at Portsmouth, then a part of the physics department, on a project involving small angle neutron scattering of nucleosomes. This began Geoff’s interest in protein-DNA interactions which remained a research focus for the rest of his career.

After Portsmouth, Geoff held post-doctoral research positions at both Cambridge, working on non-standard DNA base pairing, and EMBL where he began his research into bacteriophage Gene V proteins. In 1987, Geoff returned to the Biophysics group at Portsmouth, by this time part of the Biology department, as a member of academic staff. Notably during the late 1980s he started his work on bacterial restriction-modification systems, which provided a rich seam of study over the coming years.

Geoff was not only a successful research scientist but a highly respected teacher to both undergraduates and his many postgraduate students, explaining complex concepts in a clear, precise manner often with some humour. Geoff was at the core of the development of the science faculty at Portsmouth, leading the RAE and later REF submissions. He was instrumental in setting up and leading the very successful Institute of Biomedical and Biological Sciences (IBBS) within the faculty, which remains the vehicle for delivering research excellence in both topics at Portsmouth.

Geoff took a phased retirement and as Emeritus remained a common sight in the Biophysics tearoom and a good friend to the many students who had passed through his laboratory.