Integrative Transport Phenomena in Chemokine Gradient Establishment (360G-Wellcome-206284_Z_17_Z)

£1,927,134

A functioning immune system relies on carefully tuned fluid, cellular and molecular transport processes. Chemokines are secreted chemoattractants that orchestrate the migration and positioning of leukocytes, and are indispensable components of all protective and pathogenic immune and inflammatory responses. Lymphatic endothelial cells (LECs) play a prime role in chemokine production and exchange with the surrounding tissues, where a combination of diffusion, advection, binding kinetics and cellular uptake result in the generation of spatial chemokine gradients that govern leukocyte migration. If chemokine gradients are not appropriately tuned, leukocytes fail to respond and immune responses are compromised. While previous research has revealed much about chemokine function at the sub-cellular level, there is little quantitative knowledge of how physical and biological mechanisms interact to produce functional chemokine gradients in vivo, or of how the specific characteristics of those gradients affect leukocyte behaviour. We aim to develop a comprehensive quantitative knowledge base of chemokine gradient formation and regulation using integrated experimental and modelling approaches. This will provide unprecedented insight into this complex, dynamic and critically important process, and has potential impact on vaccination and on the treatment of diseases with key immune cell contributions, such as allergy, autoimmunity, cardiovascular disease, and cancer.

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Grant Details

Amount Awarded 1927134
Applicant Surname Moore
Approval Committee Science Interview Panel
Award Date 2017-04-05T00:00:00+00:00
Financial Year 2016/17
Grant Programme: Title Collaborative Award in Science
Internal ID 206284/Z/17/Z
Lead Applicant Prof James Moore
Other Applicant(s) Prof Bindi Brook, Prof Robert Nibbs
Partnership Value 1927134
Planned Dates: End Date 2024-12-31T00:00:00+00:00
Planned Dates: Start Date 2017-12-04T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London