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Grant: Project Grant

University of Toronto

$849,150.00

An actomyosin-Arf-GEF negative feedback loop for developmental tissue dynamics

EF 2019-20

Résumé
We study how animal tissues are built, focusing on sheets of cells called epithelia. Epithelia form our skin and internal organs, and act as regulated barriers to compartmentalize the body for its functions and protection (e.g. containing digestion inside the stomach). Epithelial structure can also be amazingly dynamic. Simple tissues of the early embryo must grow and reorganize to form the body and its organs. Even in adults, the maintenance of organs from resident stem cells requires continual epithelial remodeling. Similarly, these sheets of cells undergo dynamic movements to repair wounds. Moreover, >80% of human cancers originate from epithelial tissues, and cancers worsen with epithelial breakdown and invasive cell migration. Epithelial dynamics are dictated by the behaviors of cell-cell contacts (their constriction, growth, loss and gain). We are studying a molecular mechanism that regulates these cell-cell contacts. We are elucidating how a contact grows, and how contact growth is coupled with contact constriction. Our research relies on the experimental work-horse Drosophila melanogaster (the fruit fly). We visualize molecules, cells and tissues with advanced microscopy and manipulate specific components of the system with genetics. The molecules that organize cells and tissues in Drosophila have counterparts that perform similar functions in humans, and Drosophila has major experimental advantages. Drosophila research provides rapid advances that inform strategies for regenerative medicine and cancer therapies.
Programme
Project Grant
Bénéficiaire
Emplacement
Ontario, Canada
Type de bénéficiaire
Academia
Type
Grant
Source
CIHR Funding Decisions Database

Tel que publié

Id
419065
Name
Harris Tony J
Region
Ontario
Country
Canada
Orgtype
Institution Paid; Research Institution
Instname2
Genetics
Theme2
Biomedical
Prcname2
Developmental Biology
Projecttitle
An actomyosin-Arf-GEF negative feedback loop for developmental tissue dynamics
Programtype2
Operating Grants
Orgnameinp2
University of Toronto
Cihramount2
$849,150
Cihrequipment2
$0
Programname2
Project Grant
Keyworddelim
Cell Adhesion; Cytoskeleton; Drosophila Embryogenesis; Epithelial Morphogenesis; Small G Protein Signaling
Abstract
We study how animal tissues are built, focusing on sheets of cells called epithelia. Epithelia form our skin and internal organs, and act as regulated barriers to compartmentalize the body for its functions and protection (e.g. containing digestion inside the stomach). Epithelial structure can also be amazingly dynamic. Simple tissues of the early embryo must grow and reorganize to form the body and its organs. Even in adults, the maintenance of organs from resident stem cells requires continual epithelial remodeling. Similarly, these sheets of cells undergo dynamic movements to repair wounds. Moreover, >80% of human cancers originate from epithelial tissues, and cancers worsen with epithelial breakdown and invasive cell migration. Epithelial dynamics are dictated by the behaviors of cell-cell contacts (their constriction, growth, loss and gain). We are studying a molecular mechanism that regulates these cell-cell contacts. We are elucidating how a contact grows, and how contact growth is coupled with contact constriction. Our research relies on the experimental work-horse Drosophila melanogaster (the fruit fly). We visualize molecules, cells and tissues with advanced microscopy and manipulate specific components of the system with genetics. The molecules that organize cells and tissues in Drosophila have counterparts that perform similar functions in humans, and Drosophila has major experimental advantages. Drosophila research provides rapid advances that inform strategies for regenerative medicine and cancer therapies.
Competitiondate
202003
Approvedterm2
5 yrs 0 mth
Pinamesdelim
Harris, Tony J
Approvedterm
5 ans 0 mois
Cihrcontribution2
~ $849,150~ $0~