| Grant number: | 17/25437-3 |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| Start date: | March 01, 2018 |
| End date: | February 28, 2022 |
| Field of knowledge: | Biological Sciences - Morphology - Cytology and Cell Biology |
| Principal Investigator: | Alexandre Bruni Cardoso |
| Grantee: | Mayara Carolinne Silva Botelho |
| Host Institution: | Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil |
| Associated research grant: | 14/10492-0 - Hippo-YAP as a converging pathway for biochemical and mechanical signals from the extracellular matrix during mammary gland morphogenesis and breast cancer progression, AP.JP |
Abstract Proliferation is the most conserved and fundamental attribute of a living system. It is the propagation of genetic material through cell division, more than any other factors that distinguish life from inanimate natural systems. However, most cells in our body are not dividing, but are in a state of quiescence. Why then did quiescence triumph during evolution and how is it controlled? We know that cells of complex organisms stop proliferating even in the presence of an abundance of resources. Endogenous factors that are present in the cellular microenvironment are more likely to trigger and sustain cellular quiescence. In addition, the loss of quiescence is one of the main characteristics of the Cancer. To elucidate the molecular mechanisms that underlying acquisition and maintenance of quiescence, we propose to use large-scale gene identification in cells exposed to extracellular matrix (ECM) quiescence signals. Cells from a female mouse mammary gland epithelial line will be transfected with cell cycle fluorescence probes and a CRISPR/CAS9 library, and cultured in a matrix rich in laminin-111, a cell quiescence inducing ECM protein. Cells that continue to proliferate will be sorted and sequenced (next generation sequencing) for identification of the set of knockout genes. Three to 5 targets will be chosen for validation by silencing and overexpression followed by phenotypic analysis in three-dimensional cultures. With the completion of this project, we expect to obtain crucial information on the molecular mechanisms that control quiescence in normal cells and how this regulation goes awry in Cancer. (AU) | |
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