Structural Biology
Introduction
Our research involves determining the shape, structure and dynamics of proteins and macromolecular machines to elucidate how they achieve their remarkable activities in the cell with a focus on a number of biological processes including: the conversion of light to chemical energy, bacterial pathogenesis, Alzheimer’s disease, cardiovascular disease and cancer.
In our studies we use integrated computational, biochemical and structural methods including X-ray crystallography, NMR spectroscopy and Cryo-electron microscopy in addition to spectroscopic and thermodynamic techniques. We study both soluble and membrane proteins and large macromolecular complexes.
Our overarching goal is to understand the atomic and molecular basis of biological processes in terms of the architecture, assembly, dynamics and interactions that shape life at the cellular level. We are also interested in synthetic biology, where life processes are harnessed for improving and greening industrial transformations to bring about improvements in the quality of life.
Our work underpins grand challenges in healthy ageing, antimicrobial resistance, energy, and synthetic biology where we target the macromolecular assemblies for therapeutic interventions or industrial biotechnology applications.
Structural Biology
- A) Pickersgill Group: Higher order nanotubes of bacterial microcompartment protein PduA (JBC 2014; 289(32):22377
- B) Viles Group: Amyloid-b fibres –Zn2+ induced assemblies (JMB 2016; 428(14):2832-2846)
- C) Nield Group: Structural studies of PSII-LHCII megacomplexes (Photosynth Res 2016 Accepted), iron partitioning and ferritin function (Metallomics 2013; 5(8):997-1005)
Staff
| Researcher | Title | Department |
Research Interests |
| Bessant, Prof Conrad | Professor of Bioinformatics | Biochemistry |
Bioinformatics, Proteomics, Metabolomics, Software development, Data integration |
| Darbari, Dr Vidya | Lecturer in Structural Biology | Biochemistry |
X-ray, Crystallography, Electron microscopy, Protein-protein interaction, Ribonucleoprotein complex, Gene regulation |
| Fornili, Dr Arianna | Lecturer in Computational Organic Chemistry | Biochemistry and Chemistry |
Computational chemistry, Molecular dynamics, Protein conformational changes, Cardiac muscle, Molecular modelling |
| Janes, Dr Bob |
Senior Lecturer |
Biochemistry |
Structure-function, Polypeptide toxins, Bioinformatics, 2struc, PCDDB, SRCD spectroscopy, Circular dichroism |
| Lecturer | Biochemistry |
Biochemistry, Molecular biophysics, Repeat proteins, Protein folding |
|
| Pickersgill, Prof Richard |
Head of School and Professor of Structural Biology |
Biochemistry |
Structural biology, Protein crystallography, Synthetic biology, Enzymes, Cobalamin, Biosynthesis, Bacterial microcompartments |
| Stieglitz, Dr Ben | Lecturer in Biochemistry |
Biochemistry |
Ubiquitin, Host-pathogen interaction, Anti-microbial resistance, Structural biology, Enzymology |
| Viles, Dr John | Reader in Biochemistry |
Biochemistry |
Protein misfolding, Neurodegeneration, Alzheimers, Prions, Spectroscopy, Biochemistry |
Funding
Our research receives financial support from:
- The Biotechnology and Biological Sciences Research Council
- The Medical Research Council
- The Wellcome Trust
- The Royal Society
- Japan Science and Technology Agency/CREST
- EU Marie Curie Co-Funding Actions
- The Leverhulme Trust
Our studentships are also supported by:
- The Engineering and Physical Sciences Research Council
- Conacyt
- The Biotechnology and Biological Sciences Research Council Case and KTN studentships with industrial contributions from Isogenica and Prozomix.
Publications
Saha S, Matthews D, Bessant C (2018). High throughput discovery of protein variants using proteomics informed by transcriptomics. Nucleic Acids Research
Pearce O, Delaine-Smith R, Maniati E, Nichols S, Wang J, Böhm S, Rajeeve V, Ullah D, Chakravarty P, Jones R, Montfort A, Dowe T, Gribben J, Jones L, Kocher H, Serody J, Vincent B, Connelly J, Brenton J, Chelala C, Cutillas P, Lockley M, Bessant C, Knight M, Balkwill F (2018). Deconstruction of a Metastatic Tumor Microenvironment Reveals a Common Matrix Response in Human Cancers. Cancer Discovery
Tiberti M, Pandini A, Fraternali F, Fornili A (2018). In silico identification of rescue sites by double force scanning. Bioinformatics
Perez-Riba A, Lowe A, Main E, Itzhaki L (2018). Context-Dependent Energetics of Loop Extensions in a Family of Tandem-Repeat Proteins. Biophysical Journal
Gu M, Bode D, Viles J (2018). Copper Redox Cycling Inhibits Aβ Fibre Formation and Promotes Fibre Fragmentation, while Generating a Dityrosine Aβ Dimer. Scientific Reports
Uddin I, Frank S, Warren M, Pickersgill R (2018). A Generic Self‐Assembly Process in Microcompartments and Synthetic Protein Nanotubes. Small
Lee M, Mantell J, Brown I, Fletcher J, Verkade P, Pickersgill R, Woolfson D, Frank S, Warren M (2018). De novo targeting to the cytoplasmic and luminal side of bacterial microcompartments. Nature Communications
Pluta P, Roversi P, Bernardo-Seisdedos G, Rojas A, Cooper J, Gu S, Pickersgill R, Millet O (2018). Structural basis of pyrrole polymerization in human porphobilinogen deaminase. Biochimica Biophysica Acta
Harvey J, Itzhaki L, Main E (2018). Programmed Protein Self-Assembly Driven by Genetically Encoded Intein-Mediated Native Chemical Ligation. ACS Synthetic Biology
Barritt J, Younan N, Viles J (2017). N‐Terminally Truncated Amyloid‐β(11–40/42) Cofibrillizes with its Full‐Length Counterpart: Implications for Alzheimer's Disease. Angewandte Chemie
Hashem S, Tiberti M, Fornili A (2017). Allosteric modulation of cardiac myosin dynamics by omecamtiv mecarbil. PLoS Computational Biology
Janes R (2017). PDB2CD visualises dynamics within protein structures. European Biophysics Journal
Gua S, Shevchik V, Shaw R, Pickersgill R, Garnett J (2017). The role of intrinsic disorder and dynamics in the assembly and function of the type II secretion system. Biochimica Biophysica Acta – Proteins and Proteomics
Kliza K, Taumer C, Pinzuti I, Franz-Wachtel M, Kunzelmann S, Stieglitz B, Macek B, Husnjak K (2017). Internally tagged ubiquitin: a tool to identify linear polyubiquitin-modified proteins by mass spectrometry. Nature Methods
Nishimura T, Nagao R, Noguchi T, Nield J, Sato F, Ifuku K (2016). The N-terminal sequence of the extrinsic PsbP protein modulates the redox potential of Cyt b559 in photosystem II. Scientific Reports
Dove K, Stieglitz B, Duncan E, Rittinger K, Klevit R (2016). Molecular insights into RBR E3 ligase ubiquitin transfer mechanisms. EMBO Reports
Yang Y, Darbari V, Zhang N, Lu D, Glyde R, Wang YP, Winkelman J, Gourse R, Murakami K, Buck M, Zhang X (2015). Structures of the RNA polymerase-σ54 reveal new and conserved regulatory strategies. Science