Professor Colin Watts
FRS FRSE FMedSci
Emeritus Professor of Immunobiology
Cell Signalling and Immunology, School of Life Sciences
Colin Watts was Professor of Immunobiology at Dundee from 1998 to 2018. Prior to that (1986-1998) he was Lecturer and then Reader in the Department of Biochemistry, Dundee. He trained at the University of Bristol, University of Sussex and as an EMBO Long-term Fellow at the University of California, Los Angeles. He held a Beit Memorial Fellowship at the MRC Laboratory of Molecular Biology Cambridge (1982-86). He has been elected a Member of EMBO, Fellow of the Royal Society of Edinburgh, Fellow of the Royal Society and Fellow of the Academy of Medical Sciences.
Over a 30 year period in Dundee the Watts lab made advances at the interface of immunology and cell biology and uncovered some of the basic features of the pathways of antigen capture, processing and presentation to T lymphocytes. The lab was one of the first to investigate this key area of immunology using biochemical and cell biological concepts and approaches. The initial focus was on class II MHC molecules which present protein antigens to, and activate, CD4 T cells. We showed that MHC class II molecules are loaded with peptide antigen during biosynthesis and that once delivered to the cell surface most class II/peptide complexes are very stable in spite of continuous endocytosis and recycling. We found that antigen processing can be modulated by bound antibodies and that this can enhance or suppress presentation of different parts of the antigen to CD4 T cells. We found that an unusual proteolytic enzyme termed asparagine endopeptidase contributes to both antigen processing and preparation of the class II MHC molecule for antigen binding.
We studied key antigen presenting cells called dendritic cells and showed how they respond to bacterial and other foreign products by activating an endocytic pathway termed macropinocytosis which in turn enhanced a distinct type of antigen presentation, termed 'cross-presentation'. Cross-presentation activates Class I MHC driven CD8 T cell responses for example to viruses and tumours as well as to vaccines. Macropinocytosis is a distinct mode of endocytosis used not only by immune cells to capture antigen but also by cancer cells to engulf nutrients to fuel their growth. We discovered that this endocytic pathway can be distinguished from other entry routes into cells by its sensitivity to the compound amiloride, a tool adopted by many labs to study this pathway.
Some immune cells such as eosinophils combat infectious agents, for example worm parasites, by discharging toxic proteins. These toxins must be safely packaged until needed in so called granules to avoid toxicity to the eosinophil itself. We showed that safe packaging is critically dependent on a protein termed cystatin F or leukocystatin. With our collaborators we solved the structure of cystatin F, showing how it provides ‘feedback control’ of granule protease activity and how when this gene/protein is missing, normal eosinophil development fails leading to increased susceptibility to a parasitic infection. Finally we showed that many cell types can increase their capacity to degrade endocytosed material by de novo expression of lysosomal hydrolytic enzymes controlled by activation of the transcription factor STAT3.
- Reid, P.A. & Watts, C. Nature 346: 655-657 (1990). Cycling of cell-surface MHC glycoproteins through primaquine-sensitive intracellular compartments. DOI: 10.1038/346655a0
- Davidson, H.W., Reid, P.A., Lanzavecchia, A & Watts, C. Cell 67: 105-116 (1991). Processed antigen binds to newly synthesised MHC Class II molecules in antigen specific B lymphocytes. DOI: 10.1016/0092-8674(91)90575-j
- Lanzavecchia, A., Reid, P.A. & Watts, C. Nature 357: 249-252 (1992). Irreversible association of peptides with class II MHC molecules in living cells. DOI: 10.1038/357249a
- West, M.A., Lucocq, J. & Watts, C. Nature 369: 147-151 (1994). Antigen processing and class II MHC peptide loading compartments in human B lymphoblastoid cells. DOI: 10.1038/369147a0
- Norbury, C.C., Hewlett, L.J., Prescott, A.R., Shastri, N. & Watts, C. Immunity 3: 783-791 (1995). Class I MHC presentation of exogenous soluble antigen via macropinocytosis in bone marrow macrophages. DOI: 10.1016/1074-7613(95)90067-5
- Manoury, B., Hewitt, E.H., Morrice, N., Dando, P.M., Barrett, A.J. & Watts, C. Nature 396: 695-699 (1998). An asparaginyl endopeptidase processes a microbial antigen for class II MHC presentation. DOI: 10.1038/25379
- West, M.A., Wallin, R.P., Matthews, S.P., Svensson, H.G., Zaru, R., Ljunggren, H-G., Prescott, A.R. & Watts, C. Science 305: 1153-1157 (2004). Enhanced dendritic cell antigen capture via Toll-like receptor induced actin remodeling. DOI: 10.1126/science.1099153
- Moss, C.X., Tree, T.I. & Watts, C. EMBO J. 26: 2137-2147 (2007). Reconstruction of a pathway of antigen processing and class II MHC peptide capture. DOI: 10.1038/sj.emboj.7601660
- Matthews, S.P., McMillan, S.J., Colbert, J.D. Lawrence, R.A. & Watts, C. Immunity 44: 795-806 (2016). Cystatin F ensures eosinophil survival by regulating granule biogenesis. DOI: 10.1016/j.immuni.2016.03.003
- Martinez-Fabregas, J. Prescott, A.R., van Kasteren, S.I., Pedrioli, D.L., McClean, I. Reinheckel, T., Poli, V. & Watts, C. Nature Communications 9: 5343- (2018). Lysosomal protease deficiency or substrate overload induce an oxidative stress-mediated, STAT3-dependent pathway of lysosomal homeostasis. DOI: 10.1038/s41467-018-07741-6
|Fellow of the Academy of Medical Sciences||2009|
|Fellow of the Royal Society||2005|
|Fellow of the Royal Society of Edinburgh||1999|
|Member of the European Molecular Biology Organisation||1996|