BBSRC David Phillips Fellowship: The role of ARAP proteins in cell motility
Lead Research Organisation:
Babraham Institute
Department Name: Inositide
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
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.
People |
ORCID iD |
| Sonja Vermeren (Principal Investigator) |
Publications
Craig HE
(2010)
ARAP3 binding to phosphatidylinositol-(3,4,5)-trisphosphate depends on N-terminal tandem PH domains and adjacent sequences.
in Cellular signalling
Gambardella L
(2013)
Molecular players in neutrophil chemotaxis--focus on PI3K and small GTPases.
in Journal of leukocyte biology
Gambardella L
(2013)
Phosphoinositide 3-OH kinase regulates integrin-dependent processes in neutrophils by signaling through its effector ARAP3.
in Journal of immunology (Baltimore, Md. : 1950)
Gambardella L
(2011)
The GTPase-activating protein ARAP3 regulates chemotaxis and adhesion-dependent processes in neutrophils.
in Blood
Gambardella L
(2010)
PI3K signaling through the dual GTPase-activating protein ARAP3 is essential for developmental angiogenesis.
in Science signaling
Kartopawiro J
(2014)
Arap3 is dysregulated in a mouse model of hypotrichosis-lymphedema-telangiectasia and regulates lymphatic vascular development.
in Human molecular genetics
Raaijmakers JH
(2007)
The PI3K effector Arap3 interacts with the PI(3,4,5)P3 phosphatase SHIP2 in a SAM domain-dependent manner.
in Cellular signalling
Song Y
(2014)
ARAP3 functions in hematopoietic stem cells.
in PloS one
Zudaire E
(2011)
A computational tool for quantitative analysis of vascular networks.
in PloS one
| 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 Institutes of Health (NIH) |
| Department | 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 Institutes of Health (NIH) |
| Department | 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 |