BBSRC David Phillips Fellowship: The role of ARAP proteins in cell motility

Lead Research Organisation: Babraham Institute
Department Name: Signalling

Abstract

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Technical Summary

My working hypothesis is that ARAP proteins are regulating cross-talk between P13K, Rap, Rho and Arf small GTPases during cell motility. I will address this in four individual approaches: 1) Functional comparison of ARAP1, 2 and 3 using in vitro approaches and transfection-based assays. 2) Creation of ARAP3-/- keratinocyte and neutrophil model systems. 3) Analysis of ARAP3-/- keratinocytes with respects to cellular motility and adhesion. 4) Analysis of ARAP3-/- neutrophils with regards to chemotaxis, but also phagocytosis and the NADPH oxidase.
 
Description This work has allowed us to appreciate that ARAP3 is an important regulator of endothelial cells and neutrophils. Due to its role downstream of PI3K in endothelial cells, loss of ARAP3 is embryonically lethal leading due a severe angiogenesis defect. In neutrophils, ARAP3 regulates adhesion dependent processes including cell migration, most likely by modulating inside-out signalling of beta2 integrins.
Exploitation Route Our findings are of direct relevance to the biotech / pharmaceutical sector and we are starting to explore shared interests already.
Sectors Pharmaceuticals and Medical Biotechnology

 
Description Our findings were presented to scientific audiences at conferences and by publication in peer reviewed journals. We presented to the wider public by press releases, that were picked up by some local publications, and I gave a podcast interview with Science Signaling, that can still be accessed online. This was basic biomedical research, and whilst the work will be indirectly contributing to the types of impacts that are listed below, immediate, direct impacts cannot easily be attributed
First Year Of Impact 2011
Sector Pharmaceuticals and Medical Biotechnology,Other
 
Description Industrial CASE CVS
Amount £98,212 (GBP)
Funding ID BB/R505651/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 10/2017 
End 09/2021
 
Description MRC Precision Medicine PhD Doctoral Training Programme studentship
Amount £88,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 09/2019 
End 08/2023
 
Description Project Grant
Amount £457,820 (GBP)
Funding ID MR/M023060/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 09/2015 
End 08/2018
 
Description Wellcome Trust University of Edinburgh Institutional Support Fund
Amount £34,800 (GBP)
Organisation Wellcome Trust 
Department Wellcome Trust Institutional Strategic Support Fund
Sector Charity/Non Profit
Country United Kingdom
Start 04/2014 
End 10/2015
 
Description Collaboration with a lab in the USA 
Organisation Columbia University
Country United States 
Sector Academic/University 
PI Contribution We conducted research
Collaborator Contribution They contributed genetically modified mice
Impact We have published together
Start Year 2009
 
Description Collaboration with a laboratory in Germany 
Organisation Ludwig Maximilian University of Munich (LMU Munich)
Country Germany 
Sector Academic/University 
PI Contribution We contributed experiments
Collaborator Contribution They contributed experiments
Impact We published together
Start Year 2009
 
Description Collaboration with a laboratory in Hungary 
Organisation Semmelweiss University
Country Hungary 
Sector Academic/University 
PI Contribution we contributed research
Collaborator Contribution they contributed research
Impact We published together.
Start Year 2010
 
Description International collaboration with NIH National Cancer Institute 
Organisation National Cancer Institute (NCI)
Country United States 
Sector Public 
PI Contribution The research pursued for this fellowship has resulted in an international collaboration which already led to publications in peer-reviewed journals.
Collaborator Contribution intellectual input
Impact two research papers and a book chapter
Start Year 2009
 
Description allantois explants 
Organisation National Cancer Institute (NCI)
Country United States 
Sector Public 
PI Contribution We provided micrographs of allantois explants for generation and optimisation of this new tool
Collaborator Contribution Generation of a computational analysis tool for complexity of networks generated by sprouting angiogenesis
Impact Pub Med ID: 20978237 This collaboration involves biologists and a mathematician
Start Year 2009
 
Description Press Release Science Signalling 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Our recent Science Signaling paper was chosen for broadcasting by podcast by the editors of Science Signaling. After recording the interview, we also put together a press release, to co-incide with the paper appearing. We had further enquiries from several journalists. I understand the work was cited in some local papers and in 'Business Weekly'.

This has publicised our work more widely than the publication in a scientific journal alone would have.
Year(s) Of Engagement Activity 2010
URL http://stke.sciencemag.org/content/suppl/2010/10/22/3.145.pc19.DC1
 
Description Schools Open Days 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Type Of Presentation Paper Presentation
Geographic Reach International
Primary Audience Schools
Results and Impact Yearly open day aimed at local GCSE and 'A'-level students aimed to give them an idea of scientific research At yearly Schools Open Day small groups of local students were hosted by the lab, given a short talk about our work and supervised to do a short hands-on experiment in the lab. Projects included genotyping, protein extractions, staining tissue culture cells, looking for phases of cell division under the microscope etc. Talks and short hands-on projects

no actual impacts realised to date
Year(s) Of Engagement Activity 2006
 
Description outcome dissemination 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Poster Presentation
Geographic Reach International
Primary Audience Schools
Results and Impact The work carried out with the help of this fellowship has been communicated to the public at a number of international conferences as poster and in talks; the fellowship holder also talked about this work in several invited seminars. In addition, one piece of work was chosen for a podcast by the editorial team of the journal in which the work has been published. Lay science talk aimed at school teachers (including science teachers) visiting the Babraham Institute Talk

no actual impacts realised to date
Year(s) Of Engagement Activity 2011