Research themes

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

Chemical Biology
Chemical Biology is the application of the chemical tools and concepts to biological problems. Within the Astbury Centre, chemists are engaged in highly interdisciplinary and collaborative research programmes between chemists and biologists to address a wide of biological, chemical and medical problems: to design and synthesise new drugs; to use small molecules as tools to understand biological mechanisms; to pioneer new approaches in synthetic biology; and to exploit designer enzymes in synthetic chemistry. We have superb facilities for chemical biology including a computer cluster dedicated to ligand design, a facility for screening compound libraries for biological function, a suite dedicated to the high-throughput synthesis of small molecules, and integrated synthetic and biological laboratories. We exploit these facilities, in conjunction with biophysical and structural approaches, to address a wide range of problems of direct relevance to society

Structural Biology
Structural Biology is the study of the 3-dimensional structure of macromolecules - the molecules of life. Since macromolecular structure is intimately linked to function, both the theoretical aspects of macromolecular folding as well as the functional implications of the native structures are being investigated. Within the Astbury Centre, a range of techniques is used to elucidate structures such as X-ray crystallography, NMR, and electron microscopy, as well as modeling, and a host of complementary biophysical techniques such as analytical ultracentrifugation, isothermal titration calorimetry, CD, SPR, fluorescence etc. We take advantage of our superb 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, developmental biology and more.

Bionanosciences

Biophysics
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. Research within the Astbury Centre embraces using the widest possible array of biophysical methods to determine the specificity, rates, and equilibrium free energies of protein-protein, protein-nucleic acid 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 and 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
To complement the biophysical approach, we also study molecular interactions in the context of the whole cell. Access to the latest bioimaging equipment allows us to apply techniques such as confocal and electron microscopy to investigate cell biology. These studies are further complemented by biochemical and molecular approaches to investigate protein-nucleic acid, protein-protein and protein-lipid interactions within cells, for example using immunoprecipitation, protein tag and proteomic technologies.
The study of viruses is a strong focus, we are interested in the mechanisms of virus replication and pathogenesis in a variety of human and animal pathogenic viruses. This, coupled with a developing activity in structure-based drug design targeting virus proteins, provides a broad research base that will hopefully lead to new therapeutic approaches. Another focus is the molecular and cellular basis of amyloid disease, with ongoing research into Alzheimer's disease, prion diseases and dialysis-related amyloidosis. This research investigates how amyloidogenic precursors are generated and how amyloid formation results in cell death and tissue damage.

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