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.
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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 |
Partnership Value | 250000 |
Planned Dates: End Date | 2019-06-30T00:00:00+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 |