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.

Publications

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Aucher A (2013) MicroRNAs transfer from human macrophages to hepato-carcinoma cells and inhibit proliferation. in Journal of immunology (Baltimore, Md. : 1950)

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Benninger RK (2007) Fluorescence-lifetime imaging of DNA-dye interactions within continuous-flow microfluidic systems. in Angewandte Chemie (International ed. in English)

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Borhis G (2013) A peptide antagonist disrupts NK cell inhibitory synapse formation. in Journal of immunology (Baltimore, Md. : 1950)

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Byrne SM (2012) Cathepsin B controls the persistence of memory CD8+ T lymphocytes. in Journal of immunology (Baltimore, Md. : 1950)

 
Title Book: The Compatibility Gene 
Description The Compatibility Gene is a scientific adventure story set in a new field of genetic discovery - that of the crucial genes that define our relationships, our health and our individuality. Here, Daniel M Davis, one of the leading scientists in the field, tells us the story of its grounbreaking developments that have the potential to change us all We each possess a similar set of around 25,000 human genes. Yet a tiny, distinctive cluster of these genes plays a disproportionately large part in how our bodies work. These few genes, argues Daniel M. Davis, hold the key to who we are as individuals and our relationship to the world: how we combat disease, how our brains are wired, how attractive we are, even how likely we are to reproduce. In The Compatibility Gene, one of our foremost immunologists tells the remarkable history of these genes' discovery and the unlocking of their secrets. From the British scientific pioneers who, during the Second World War, struggled to understand the mysteries of transplants and grafts, to the Swiss zoologist who devised an entirely new method of assessing potential couples' compatibility based on the smell of worn T-shirts, Davis traces what is nothing less than a scientific revolution in our understanding of the human body: a global adventure spanning some sixty years. Davis shows how the compatibility gene is radically transforming our knowledge of the way our bodies work - and is having profound consequences for medical research and ethics. Looking to the future, he considers the startling possibilities of what these wondrous discoveries might mean for you and me. 
Type Of Art Creative Writing 
Year Produced 2014 
Impact The Compatibility Gene was longlisted for the 2014 Royal Society Winton Science Book Prize, short-listed for the Society of Biology book prize and received a series of outstanding reviews in The Times, New York Times, Guardian, New Scientist, New Statesman, BBC Focus, Nature and so on. It was picked by Bill Bryson for the Guardian's Books of the Year feature 2013 and was included in Nature's features on Summer Books 2014 and Autumn Books 2014. A humorous piece by the popular journalist Tim Dowling, highlighted The Compatibility Gene on the front cover of The Guardian (8th Sept 2013) and featured in Dowling's own book How to be a Husband (2014). Davis discussed The Compatibility Gene on BBC Breakfast TV, as well as on US TV (The Circle, MS-NBC), the Guardian science podcast and several radio stations. Nature profiled Davis twice in 2013; in a feature on scientists who write books (Get the word out) and for his research discoveries. He has published articles in Scientific American, BBC Focus magazine, Physics World and previously won the Oxford University Press Science Writing Prize. In 2014, Davis presented The Compatibility Gene at the Hay Festival (Wales stage; 700 attendees), The Royal Institution in London (400 attendees), Edinburgh Science Festival, Manchester Science Festival, York's Festival of Ideas, Latitude music festival and many other events. 
URL http://www.amazon.co.uk/The-Compatibility-Gene-Daniel-Davis/dp/1846145147/ref=tmm_hrd_title_0
 
Description BBSRC funding
Amount £279,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 10/2006 
End 10/2009
 
Description EC Marie Curie award
Amount £90,000 (GBP)
Organisation Marie Sklodowska-Curie Actions 
Sector Charity/Non Profit
Country Global
Start 01/2009 
End 01/2010
 
Description MRC program grant renewal
Amount £1,821,556 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 10/2011 
End 10/2016
 
Description Manchester Collaborative Centre
Amount £2,000,000 (GBP)
Organisation University of Manchester 
Department Manchester Collaborative Centre for Inflammation Research (MCCIR)
Sector Academic/University
Country United Kingdom
Start 11/2012 
End 10/2017
 
Description Merck Abacus Program
Amount £150,000 (GBP)
Organisation Merck 
Sector Private
Country Germany
Start 01/2008 
End 01/2009
 
Description Research Excellence Award
Amount £150,000 (GBP)
Organisation Imperial College London 
Department Imperial College Trust
Sector Charity/Non Profit
Country United Kingdom
Start 10/2008 
End 10/2011
 
Description Wellcome Trust Investigator award
Amount £1,800,000 (GBP)
Organisation Wellcome Trust 
Department Wellcome Trust Bloomsbury Centre
Sector Charity/Non Profit
Country United Kingdom
Start 10/2016 
End 10/2021
 
Title New imaging technologies have been developed 
Description new approaches to imaging immune cell activation have been developed 
Type Of Material Improvements to research infrastructure 
Provided To Others? No  
Impact Several labs world-wide have taken up some of the new imaging approaches we have developed 
 
Title Nk cell and 221 transfectants 
Description Several cell line transfectants were made and these have been distributed to many labs in several countries. 
Type Of Material Cell line 
Year Produced 2009 
Provided To Others? Yes  
Impact Several cell line transfectants were made and these have been distributed to many labs in several countries. 
 
Description Communicating complex network information by intercellular transfer of macrophage proteins and RNA 
Organisation Merck
Country Germany 
Sector Private 
PI Contribution Communicating complex network information by intercellular transfer of macrophage proteins and RNA
Collaborator Contribution Communicating complex network information by intercellular transfer of macrophage proteins and RNA
Impact Communicating complex network information by intercellular transfer of macrophage proteins and RNA
Start Year 2008
 
Description Understanding and manipulating Antibody Dependent Cell Cytotoxicity (ADCC) by human Natural Killer (NK) cells 
Organisation MedImmune
Country United States 
Sector Private 
PI Contribution This is a new grant funded by the MRC in collaboration with the company MedImmune
Collaborator Contribution Reagents and expertise is provided.
Impact This is a new funded grant, work is just now beginning. In addition, a postdoc from my lab will take up a new permanent post at this company
Start Year 2009
 
Description Public Lectures / Interviews 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Davis discussed The Compatibility Gene on BBC Breakfast TV, as well as on US TV (The Circle, MS-NBC), the Guardian science podcast and several radio stations. Nature profiled Davis twice in 2013; in a feature on scientists who write books (Get the word out) and for his research discoveries. He has published articles in Scientific American, BBC Focus magazine, Physics World and previously won the Oxford University Press Science Writing Prize. In 2014, Davis presented The Compatibility Gene at the Hay Festival (Wales stage; 700 attendees), The Royal Institution in London (400 attendees), Edinburgh Science Festival, Manchester Science Festival, York's Festival of Ideas, Latitude music festival and many other events.

Public lectures were extremely well attended
Year(s) Of Engagement Activity 2006,2007,2008,2009,2010,2011,2012,2013,2014,2015,2016
URL http://www.davislab.ls.manchester.ac.uk/book/articlesandvideos/
 
Description Scientific American article 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact I published a major article in this research area in Scientific American magazine which has a worldwide subscription of over one million.

This was the most downloaded article at the time of publication
Year(s) Of Engagement Activity 2006
 
Description Summary of media activities 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Davis keenly engages in making immunology accessible to non-specialist audiences. In August 2013, his popular-level book about the immune system entitled The Compatibility Gene was published by Penguin. The book received praise from Steven Pinker (Harvard), Steve Jones (UCL), Armand Leroi (Imperial) and Peter Doherty (Nobel Laureate), and had fantastic reviews, including in The Times, New York Times, Guardian, New Scientist, New Statesman, BBC Focus and Nature. It was picked by Bill Bryson in the Guardian's Books of the Year feature. An article about the book was also written by the popular journalist Tim Dowling, highlighted on the front cover of the Guardian (8th Sept 2013), and was discussed by comedian Russell Brand. The book and these articles also brought awareness to Anthony Nolan, the bone marrow transplantation charity.
In 2013, Davis discussed the immune system and genetics with Bill Turnbull and Susannah Reid on BBC Breakfast TV, watched by over 1 million, and also on live US TV on The Circle, MSNBC. In 2013, Davis did over 15 radio interviews including several BBC radio stations, NPR California and Radio New Zealand. The Smithsonian Institute (USA) published a profile of Davis in 2013 and Nature magazine also profiled Davis in its feature on scientists who write books (Get the word out, Nature, 504, 177-179, 2013).
In 2006, Davis published a major article - Secrets of the Immune Synapse - in Scientific American magazine, which has a worldwide readership of 1 million. In 2014, he published an article on the frontiers of immunology in BBC Focus magazine. He has been interviewed for features in New Scientist, The Guardian, The BMJ and various TV programs have solicited his advice. The BBC filmed an experiment performed in his laboratory for broadcast in 'The History of Transplantation', first shown on BBC FOUR, Sept 3rd 2008. He has given many interviews for international science magazines including in Spain, France and Portugal, on US Public Radio, and Australian radio. With Prof. Paul French (Physics, Imperial College), he presented his research at the Royal Society Summer Exhibition in 2003. In 2000, he won the Oxford University Press Science Writing Prize.
Davis has given numerous public lectures in immunology, including four at The Royal Institution. In 2008, Baroness Susan Greenfield commented in a letter that Davis's Friday Evening Discourse was 'really one of the most enjoyable in years'. Davis has presented his research at the Edinburgh, Manchester and Cheltenham Science Festivals, at Science Show Off events, on the Guardian science podcast, at a TED youth conference for ~500 6th formers, York's Festival of Ideas and at Latitude music festival (where he will return in 2017). Davis enjoys a close relationship with the Hay Festival where he has presented his own work as well as chaired and helping arrange many other science speakers (8 events in 2016), including Steve Jones, Jeremey Farrar and Martin Rees. Davis has written a second popular-level book about the immune system which will be published by Penguin Random House late 2017/early 2018.
Year(s) Of Engagement Activity 2013,2014,2015,2016,2017