Immune cell communication facilitated by the supramolecular organisation and intercellular exchange of surface proteins
Lead Research Organisation:
Imperial College London
Department Name: Biological Sciences
Abstract
I am particularly keen to play a useful role in a public discussion of science. I have an article on the IS in press at Scientific American magazine (scheduled for late Summer 2005) which has a worldwide subscription of over one million. For this article, I interviewed many colleagues for their stories surrounding the earliest observations and discussions on the IS. In addition, I give public lectures at the Royal Institution (2000 and 2005), where I was made an honorary Life Member as part of the ?Scientists for the New Century? program in 2000. Together with Prof. Paul French (Physics Department), I presented our research at the Royal Society Summer Exhibition in 2003. In 2000, I won the Oxford University Press/ Times Higher Education Supplement Science Writing Prize, and my article was published in The Times Higher Education Supplement. In 2003, my research program featured in BBSRC Business quarterly magazine. In 2003 and 2004, feature articles were written about our research in Biophotonics International and in 2002 our work was featured in Optics & Photonics News . In 2000, The Times newspaper published a feature article on me, and my research, entitled ?Hot on the trail of Natural Killer cells?.
Technical Summary
Many of the key cell surface molecules involved in immune cell surveillance are identified and one important new scientific frontier is to understand where and when each protein-protein interaction occurs to regulate cell functions. Thus, imaging has a major role to play in contemporary cell biology and has shown that immune cell communication is often accompanied by the segregation of proteins at immunological synapses and by the intercellular transfer of surface proteins. I now propose to study the functional consequences of target cell acquisition of NK cell proteins and of NK cell acquisition of target cell proteins. For example, tagging targets could eliminate repeated scanning of the same cell. In addition, we recently found that NK cells lyse LPS-activated macrophages whereas un-activated macrophages trigger NK cell cytokine secretion and not cytotoxicity. This provides an important physiological system in which to test how the organisation of NK cell synapses lead to different effector responses. I will also examine thresholds in the level of expression of inhibitory and activating proteins that regulate organisation of synapses and examine the role of synapse organisation in controlling signaling events. Broadly, our understanding of how the spatio-temporal organisation of molecules facilitates intercellular communication is only just beginning and using a combination of novel and commercial microscope techniques, we aim to lead research in this for specific immune cell interactions.