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Molecular Control of Adhesion-Free Migration (360G-Wellcome-204747_Z_16_Z)

Many cells have the capacity of directed motion, which is essential for several physiological and pathological processes, including development, immune-response, and metastasis. During canonical, focal adhesion-based migration, actin dynamics are converted to traction force through integrin-based anchors to the substrate. However, integrins are dispensable for in vivo and 3D-confined migration of various cell types. Recently, an alternative migration mode was discovered, during which propulsion forces are generated through non-specific friction between the cell cortex and its substrate. However, nothing is known about the molecular mechanism underlying friction-driven migration. I will elucidate this process, first by performing a candidate-based screen and state-of-the-art microfabrication assays to identify the molecules responsible for generating friction. Next, I will create knock-out zebrafish lines to determine the in vivo relevance of friction-driven migration. Finally, I will study how cells transition between adhesive and adhesion-free migration, which is crucial e.g. during cancer progression. To identify the key processes underlying these transitions, I will perform live cell microscopy of friction-generating and adhesion molecules and integrate my findings into a mathematical model of cell migration. Ultimately, this project will shed light on a newly uncovered migration mode that is likely of fundamental importance for in vivo cell motility.

£250,000

09 Nov 2016

Grant details
Amount Awarded 250000
Applicant Surname Bodor
Approval Committee Basic Science Interview Committee
Award Date 2016-11-09T00:00:00+00:00
Financial Year 2016/17
Grant Programme: Title Sir Henry Wellcome Postdoctoral Fellowship
Internal ID 204747/Z/16/Z
Lead Applicant Dr Dani Bodor
Planned Dates: End Date 2021-02-01T00:00:00+00:00
Planned Dates: Start Date 2017-02-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London
Sponsor(s) Prof Mark Marsh
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