Cel The most intriguing phenomenon in cancer research is the ability of tumour cells to spontaneously migrate away from the primary tumour and metastasize. Metastases are strongly related to poor prognosis and reduced patient survival. Therefore, studying motility properties of cancer cells may benefit the development of therapeutic methods, and can hopefully contribute to improved survival.Cancer cell motility is achieved by motility structures such as lamellipodia, filopodia and blebs. Blebs are large, round deformations of the cell, mostly driven by hydrostatic pressure that involve changes in the actomyosin cortex. While the mechanical process of bleb formation and retraction is pretty much known, its dependence on internal and external signalling is still missing. In this research we focus on the relations between signalling, blebbing and cell migration, using both experimental data and system-level modelling.The Met tyrosine kinase is an endogenous receptor that normally initiates directional motion, needed for various homeostatic tasks such as embryogenesis and wound healing. High levels of Met were shown to be related to malignancy and metastases. In the proposed research we will study Met amplifications and activating mutations, and their influence on cell shape, motility, tumourigenesis and metastasis, both in vitro and in vivo, using advanced imaging modalities.The experimental results will be used to construct a mathematical model. which couples membrane signalling to actual membrane protruding forces such as hydrostatic pressure and cortical tension, and to the overall cell motion. This allows us to learn how directional motion is achieved by apparently random blebbing and how they are both connected to cellular signalling. This model can also be used to test and predict the effects of different genetic, epigenetic and environmental conditions on the cell’s shape and motility, and will hopefully advance new strategies in metastasis prevention. Dziedzina nauki natural sciencesbiological sciencesdevelopmental biologynatural sciencesbiological sciencesgeneticsmutationnatural sciencesphysical sciencesclassical mechanicsfluid mechanicsfluid staticsmedical and health sciencesclinical medicineoncologynatural sciencesmathematicsapplied mathematicsmathematical model Program(-y) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Temat(-y) FP7-PEOPLE-2009-RG - Marie Curie Action: "Reintegration Grants" Zaproszenie do składania wniosków FP7-PEOPLE-2010-RG Zobacz inne projekty w ramach tego zaproszenia System finansowania MC-IRG - International Re-integration Grants (IRG) Koordynator TEL AVIV UNIVERSITY Wkład UE € 100 000,00 Adres RAMAT AVIV 69978 Tel Aviv Izrael Zobacz na mapie Rodzaj działalności Higher or Secondary Education Establishments Kontakt administracyjny Einat Ron (Ms.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych
