The Roslin Institute
Dr Gill’s graduate training was in protein analysis by ion mobility mass spectrometry, thereby initiating a long standing interest in the application of mass spectrometric methods, including proteomic and metabolomic workflows, to the analysis of biological problems. Dr Gill’s core research has focused on defining how the structures and interactions of proteins contribute to the function, dysfunction, folding and misfolding of those proteins. A key feature of Dr Gill's research has been the application of diverse biochemical and biophysical assays, as well as multiple molecular dynamics simulations, to understand a variety of biologically important questions. For several years, Dr Gill’s main research area was neurodegenerative, protein misfolding diseases and Dr Gill has published a range of research articles pertaining to prion disease biology. However, Dr Gill has also worked on the structure and functions of proteins from viruses, bacteria, parasites and the mammalian and avian immune systems. Current research themes are focussed on:
1. The control of protein translation. Gene expression is regulated partly at the level of transcription, but there is substantial regulation at the level of translation. We are applying mass spectrometric methods to investigate how modifications to ribosomes regulate the expression of specific protein subsets, particularly under conditions of stress or disease or in different parts of the cell.
2. Bacterial cell envelope. The Tol-Pal system, a conserved network of seven co-transcribed proteins, contributes to the stability of the cell envelope that is fundamental to the homeostasis and integrity of Gram negative bacteria. We are investigating the role of key proteins in the orchestration of events leading to cell envelope, knowledge which will provide new concepts towards the design of antibiotics that would destabilize the cell envelope.
3. Metabolomics in health and disease. We have developed or are developing a variety of targeted assays for key metabolites, including monoamine neurotransmitters, steroids, members of the one carbon metabolism pathway, specific fatty acids and vitamin D metabolites. We are also developing non-targeted metabolomics workflows to understand the role of key small molecules in modulating or controlling a variety of normal or pathogenic biological processes.
4. Understanding protein structure and function. As a hub for protein chemistry at The Roslin Institute, we undertake a large amount of collaborative work to characterise proteins (and small molecule metabolites) derived from a variety of pathogens as well as the animal hosts that they attack. For example, we have recently investigated metabolic changes that are caused by knockout of the HPRT1 gene in rats, we have determined structural aspects of the recognition of Theileria-derived peptides by CD8 T-cells and have supported efforts to express and purify important immune-modulatory molecules from the eggs of transgenic hens.
In addition to leading his research team, Dr Gill heads the Proteomics and Metabolomics Facility at the Roslin Institute.