... understanding life in molecular detail

Research themes

The current research priorities of the Centre are divided into four major themes:

Chemical Biology
Chemical Biology Chemical Biology is the application of chemical tools and approaches to address biological problems. Within the Astbury Centre, chemists are engaged in highly interdisciplinary and collaborative research programmes to address a wide range of biological, chemical and medical problems. These include the design and synthesis of new drugs, the development and exploitation of small molecule tools to interrogate biological mechanisms, pioneering new approaches in synthetic biology and engineering new enzymes for use in synthetic chemistry.

We have superb facilities for Chemical Biology including integrated synthetic and biological laboratories, a computer cluster dedicated to ligand design, a facility for screening compound libraries for biological function; and a suite dedicated to the high-throughput synthesis of small molecules. We exploit these facilities, in conjunction with biophysical, structural and cellular approaches, to address a wide range of problems of direct relevance to society.

Structural Biology
Structural Biology The Astbury Centre has a strong history in structural studies from small molecules to large protein complexes. Bill Astbury’s definition of the alpha-helix and beta-sheet structures within proteins laid the foundations for the high resolution structural studies of bio-molecules that are carried out in the Centre today.

Understanding the structure of a protein or protein complex is fundamental to underpinning drug design and understanding the relationship between structure and function. The Astbury Centre has a wealth of expertise in X-ray crystallography, nuclear magnetic resonance spectroscopy (NMR), atomic force microscopy (AFM) and electron microscopy and this structural information is complemented by biophysical techniques such as analytical ultracentrifugation, isothermal titration calorimetry, circular dichroism spectroscopy (CD), surface plasmon resonance (SPR), and fluorescence. We take advantage of our excellent modern facilities, along with the many cross-disciplinary collaborations within the Centre, to investigate the structural biology of aspects of life sciences such as enzyme mechanisms, membrane proteins, molecular motors, virus biology, molecular dynamics, protein folding and more.

Biophysics
Biophysics picture The understanding of life requires a detailed knowledge of the structure of biological macromolecules and how they interact with each other and with molecules in the living cell. Our researchers exploit the widest possible array of biophysical methods to determine the specificity, rates, and equilibrium free energies of protein-protein, protein-nucleic acid, proteinlipid and protein-ligand interactions. Techniques such as Surface Plasmon Resonance, Isothermal Titration Calorimetry and Fluorescence-Based Assays (intensity and anisotropy) are used to elucidate binding constants, whilst structural methods including Circular Dichroism, Ion Mobility Mass Spectrometry and NMR reveal information about conformational changes during binding. Single molecule methods, including Fluoresence Resonance Energy Transfer (FRET) and Force Spectroscopy are also being used to reveal new information about protein stability and force-induced conformational changes. Combined with insights from molecular dynamics simulations and mathematical modelling, our aim is to use state-of-the-art biophysical methods to develop new approaches able to elucidate how macromolecular recognition is controlled within cells to the exquisite sensitivity required for healthy life.

Molecular interactions in cells
Molecular Interactions in Cells To complement analyses using biophysical approaches in vitro, researchers in the Astbury Centre also study molecular interactions in the context of the whole cell.

Protein-nucleic acid, protein-protein and protein-lipid interactions within cells are investigated using biochemical approaches such as immunoprecipitation, purification via protein tags and the application of proteomic technologies.

Within the Astbury Centre these methods are complemented by a range of state-of-the-art bio-imaging equipment to investigate the biology of cells at different resolutions. Populations of cells are interrogated by flow cytometry and cell sorting. At an individual cell level, conventional light microscopy (e.g. confocal and deconvolution) studies can be complemented by super-resolution approaches (PALM/STORM and SIM) and electron microscopy (transmission, scanning and tomography). Correlative Light and Electron Microscopy (CLEM) allows the integration of datasets derived from different imaging modalities to provide unique insights into the localisation of biological molecules within cells. A confocal microscope situated in the Category III containment facility provides the opportunity to study cells infected with pathogens.

These projects and more are described in detail in the research pages of individual Centre members.

Specific Research Areas