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The Role of novel PKC Kinases in Integrin Activation

Project description

Tensin 1 condensation in regulation of integrin adhesion dynamics

Integrins are proteins that span cell membranes, which enables them to act as cell adhesion receptors, facilitating cell interactions with the extracellular matrix. Defective binding of integrins to their ligands in the extracellular matrix is linked to thrombosis, inflammation and cancer progression. While both intra- and extra-cellular mechanisms of receptor activation are known, the mechanisms regulating integrin adhesion dynamics are not fully understood. With the support of the Marie Skłodowska-Curie Actions programme, the nPKCInAction project aims to investigate the role of Tensin 1 condensation as a potential regulator of integrin adhesion dynamics. To that end, it will employ in vitro mechanistic studies, proteomic methods and advanced cell imaging in cancer cell models.

Objective

Integrins represent a family of cell adhesion receptors mediating cell interaction with the extracellular matrix ligands. Their ligand-binding activity is tightly regulated and, when defective, gives rise to thrombosis or inflammation and contributes to cancer progression. To date, the key steps of integrin activation in response to both extracellular and intracellular signals are well described, however, the counteracting processes resulting in receptor inactivation remain incompletely understood. The host laboratory has pioneered research in this area by screening to identify integrin inactivating proteins involved in neuronal disorders, cell migration and cancer. Although the novel subfamily of protein kinase C (nPKC) has emerged from these screens as putative integrin inhibitors, the role of these kinases in regulation of integrin-mediated signalling remains to be investigated. Benefiting from my strong methodological proficiency in protein kinase research and the host laboratory's extensive expertise in integrin biology in cancer, I aim to address the role of nPKCs in regulation of integrin activation from both mechanistic and pre-clinical points of view. I expect to identify new cancer relevant signalling nodes by executing mechanistic in vitro studies with specifically engineered kinase mutants, state-of-the art cancer cell biology and imaging, followed by in vivo pre-clinical cancer studies in cancer models and patient sample cohorts. The result of this innovative and interdisciplinary project will represent a valuable basis for potential design of drug targeting strategy and therapeutic intervention not only for treatment of cancer, but also of other diseases where nPKCs and integrins are implicated.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

(opens in new window) HORIZON-MSCA-2022-PF-01

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Coordinator

TURUN YLIOPISTO
Net EU contribution
€ 215 534,40
Address
YLIOPISTONMAKI
20014 Turku
Finland
Region
Manner-Suomi Etelä-Suomi Varsinais-Suomi
Activity type
Higher or Secondary Education Establishments
Links
Total cost
No data