The structure and dynamics of biological systems govern their behaviour, and in turn the central processes in all living organisms. We use a multidisciplinary approach to study the organisation of molecules, macromolecular biological complexes and the dynamic interactions in biological systems.
Investigation of the structure-function relationship in two key retinoic acid binding proteins has given insights into the mechanism of action of this important class of proteins. The work of the multidisciplinary team led by Professor Ehmke Pohl (Durham Biosciences and Chemistry) has provided new details about retinoic acid signalling pathways that are implicated in several cancers and neurodegenerative diseases. Find out more here.
Professor Tim Blower (Durham Biosciences) and a team of international collegues have reported the first structure of an anti-CRISPR associated protein Aca2. These proteins are synthesised by bacteriophages and other attacking species to counter the CRISPR-Cas defences mounted by bacteria to halt the attacking species. CRISPR proteins are widely used in bioengineering and the discovery of new anti-CRSPR associated proteins would be an important step in the development of more refined CRSPR techniques. Find out more here.
Multi-layered bacterial genome defences
The £4.6M project Multi-layered bacterial genome defences: linking molecular mechanisms to bacteria-MGE conflicts in single cells, populations, and communities was launched in 2022. Durham Biosciences's Professor Tim Blower is the Durham lead for the project which uses new interdisciplinary approaches and techniques to uncover bacterial defence systems. These systems could be exploited to tackle the spread of drug-resistant genes through the use of phages (viruses that infect bacteria). The project is led by Professor Edze Westra at University of Exeter, and includes researchers from the Universities of Durham, Manchester, Bath, Bristol, Liverpool and St Andrews.
Virus-X Consortium
As part of the EU funded Virus-X project Professor Ehmke Pohl (Durham Biosciences and Chemistry) has been exploring the strange world of viruses, also known as the Virosphere. Researchers in the Virus-X team have probed extreme environments, hunting for previously undiscovered viruses, including volcanic hot springs in Iceland (image right) and deep sea vents in the Atlantic Ocean more than 2300 m below sea level. 50 million new genes from extreme habitats have been found, and close to 1000 enzymes were selected for further characterisation. Several of these enzymes are currently being tested for use in applications ranging from protein production to the detection of pathogenic viruses such as SARS-CoV-2.
Cornish, K.A.S., Lange, J., Aevarsson, A., & Pohl, E., 2022. CPR-C4 is a highly conserved novel protease from the Candidate Phyla Radiation with remote structural homology to human vasohibins. Journal of Biological Chemistry, 298, 5.
Jasilionis, A., Plotka, M., Wang, L., Dorawa, S., Lange, J., Watzlawick, H., van den Bergh, T., Vroling, B., Altenbuchner, J., Kaczorowska, A.-K., Pohl, E., Kaczorowski, T., Nordberg, Karlsson, E., & Freitag-Pohl, S., 2023. AmiP from hyperthermophilic Thermus parvatiensis prophage is a thermoactive and ultrathermostable peptidoglycan lytic amidase. Protein Science, 32, 3.
Morris, E.R., Caswell, S.J., Kunzelmann, S., Arnold, L.H., Purkiss, A.G., Kelly, G., & Taylor, I.A., 2020. Crystal structures of SAMHD1 inhibitor complexes reveal the mechanism of water-mediated dNTP hydrolysis. Nature Communications, 11, 1.
Picton, D.M., Luyten, Y.A., Morgan, R.D., Nelson, A., Smith, D.L., Dryden, D.T.F., Hinton, J.C.D., & Blower, T.R., 2021. The phage defence island of a multidrug resistant plasmid uses both BREX and type IV restriction for complementary protection from viruses. Nucleic acids research, 49, 19.
Prior, C., Davies, O.R., Bruce, D., & Pohl, E., 2020. Obtaining Tertiary Protein Structures by the ab Initio Interpretation of Small Angle X-ray Scattering Data. Journal of Chemical Theory and Computation, 16, 3.
Ramaswamy, V. K., Musson, S. C., Willcocks, C. G., & Degiacomi, M. T. 2021. Deep learning protein conformational space with convolutions and latent interpolations. Physical Review X, 11, 1.
Rudden, L.S.P., Musson, S.C., Benesch, J.L.P., & Degiacomi, M.T., 2022. Biobox: a toolbox for biomolecular modelling. Bioinformatics, 38, 4.
Tomlinson, C.W.E., Cornish, K.A.S., Whiting, A., & Pohl, E., 2021. Structure-functional relationship of cellular retinoic acid-binding proteins i and II interacting with natural and synthetic ligands. Acta Crystallographica Section D: Structural Biology, 77.
Areas of Expertise: Microbiology, Genomics, Biochemistry, X-ray Crystallography
Research Interests
Areas of Expertise: Structural biology, Biophysics, Biochemistry, Virology
Areas of Expertise: Molecular Dynamics, Machine Learning, Computational Biophysics
Research Interests: The development of protein-protein docking methods, and techniques combining machine learning and molecular dynamics simulations to sample protein conformational spaces.
Areas of Expertise: Structural Biology
Areas of Expertise: Magnetohydrodynamics, Topological Constraints
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