Summary
Cell motility is driven by a complex network of force-generating biological machinery. The key component in this machinery is the dynamic network of filamentous actin (F-actin) and actin binding proteins (ABPs) which maintain and regulate the network. However, structural information for many ABP-actin complexes, as well as their in situ spatial distribution remain elusive. This is because ABPs cannot be easily studied in isolation, often exhibiting structural stability only when embedded in a complex filamentous network found within cells. This has hindered a complete understanding of actin network regulation in cell migration. Addressing this important question requires understanding exactly how ABPs select F-actin, and conversely how F-actin geometry recruits specific ABPs. Cryo-electron tomography (cryo-ET) can reveal both cellular ultrastructure and molecular details, but often is lower resolution than a single particle cryo-EM approach. Thus, innovative methods remain key to drive advancement in understanding in situ structures. In this fellowship I will combine my expertise of single particle cryo-electron microscopy with expertise of cryo-ET in the Schur lab to develop a novel hybrid single particle cryo-ET approach in order to reveal high-resolution structures and contextual information of ABPs bound to F-actin directly within cellular protrusions. ISTA is the ideal research institute due to abundant access to high-end electron microscopes necessary for methods development. The outcome of this action are tools for high resolution in situ structure determination and a better understanding of cell migration, a process deeply rooted in malignant metastasis. Results will be disseminated through key research conferences and high-impact open-access publications. Communication activities will be achieved through 3D rendered visual scientific illustrations targeting social media platforms and institute-organized public outreach events.
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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/101108395 |
| Start date: | 01-04-2023 |
| End date: | 31-03-2025 |
| Total budget - Public funding: | - 199 440,00 Euro |
Cordis data
Original description
Cell motility is driven by a complex network of force-generating biological machinery. The key component in this machinery is the dynamic network of filamentous actin (F-actin) and actin binding proteins (ABPs) which maintain and regulate the network. However, structural information for many ABP-actin complexes, as well as their in situ spatial distribution remain elusive. This is because ABPs cannot be easily studied in isolation, often exhibiting structural stability only when embedded in a complex filamentous network found within cells. This has hindered a complete understanding of actin network regulation in cell migration. Addressing this important question requires understanding exactly how ABPs select F-actin, and conversely how F-actin geometry recruits specific ABPs. Cryo-electron tomography (cryo-ET) can reveal both cellular ultrastructure and molecular details, but often is lower resolution than a single particle cryo-EM approach. Thus, innovative methods remain key to drive advancement in understanding in situ structures. In this fellowship I will combine my expertise of single particle cryo-electron microscopy with expertise of cryo-ET in the Schur lab to develop a novel hybrid single particle cryo-ET approach in order to reveal high-resolution structures and contextual information of ABPs bound to F-actin directly within cellular protrusions. ISTA is the ideal research institute due to abundant access to high-end electron microscopes necessary for methods development. The outcome of this action are tools for high resolution in situ structure determination and a better understanding of cell migration, a process deeply rooted in malignant metastasis. Results will be disseminated through key research conferences and high-impact open-access publications. Communication activities will be achieved through 3D rendered visual scientific illustrations targeting social media platforms and institute-organized public outreach events.Status
TERMINATEDCall topic
HORIZON-MSCA-2022-PF-01-01Update Date
31-07-2023
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