School of Biological and Chemical Sciences

Structural Biology

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

Main, Dr Ewan

Lecturer Biochemistry

Biochemistry, Molecular biophysics, Repeat proteins, Protein folding

Nield, Dr Jon

Senior Lecturer in Structural Biology, Principal Research Fellow

Biochemistry 

Structural biology, Transmission electron microscopy, Computer image-processing, 3D macromolecular modelling, Photosynthesis, Medicine 

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

 

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