Gamblin lab

Structural Biology of Disease Processes Laboratory

: Areas of interest

We determine the molecular mechanisms governing the basic function of protein complexes to better understand their role in disease processes.

Our main research tools are techniques in structural biology, principally X-ray crystallography and single particle electron microscopy, which we combine with a range of biophysics and enzyme kinetics approaches to elucidate function.

Our work falls into three areas:

1. The regulation of transcription by changes to chromatin structure. Modification complexes, for example, Polycomb Repressive Complex (PRC2), have been implicated in cancer. We are interested in understanding the allosteric mechanisms that control the activity of these complexes and how their chromatin environment influences the targeting of their activity.
2. We work on the structural and functional characterisation of the two principle surface glycoproteins of influenza: neuraminidase (NA) and hemagglutinin (HA). We use structural approaches to understand the basis of the specificity of host cell interactions. Our work is closely informed by the work of the World Influenza Centre housed at the Francis Crick Institute and is an important contribution to the influenza surveillance effort.
3. We investigate the mechanisms of the diabetes-associated kinase AMPK, which senses the energy status of the cell and triggers appropriate downstream pathways. We use protein chemistry, molecular biology and X-ray crystallography to determine the structure/function relationships that control the activation mechanisms in this enzyme with the ultimate aim of informing the development of novel drugs for targeting diabetes.