This Faculty Early Career Development Program (CAREER) research will develop new knowledge related to the structure and mechanics of living tissues and will train engineers to participate in bioengineering using targeted educational activities. The activities of genes direct the formation of tissues and organs but the proper shape, structure, and mechanical properties of the tissues are also guided by internal and external loading during development. It is known that abnormal tissue properties occur along with birth defects and cancer, but the extent that the abnormalities are genetic or occur from aberrant mechanical loads isn't known. It remains poorly understood how the mechanical and genetic factors work together to build normal tissues. The research will build an improved understanding of the underlying causes of birth defects and cancer by separating genetic from mechanical effects in tissue development. The work is an essential step toward the development of therapies to prevent or treat these diseases. The novel tools to control genetic expression and internal cell loading may also enable new strategies for tissue engineering and regenerative medicine, contributing to the progress of science and to the advancement of national health. The educational goal is to engage students from a variety of backgrounds in research. Ihe research will be integrated into: (1)opportunities for underrepresented minority high school students through the Columbia Engineering E.N.G. program; (2) career development and summer research mentoring for undergraduate women through the Columbia Engineering Summer@SEAS Program; and (3)a new course on Morphogenesis: shape and structure in biological materials aimed at introducing upper level undergraduate and graduate engineering students to research at the interface between mechanics and biology.
The project will study several mechanics-based questions about the construction of tissues and organs, specifically how actomyosin-based tension is transduced through cadherin-based cell-cell contacts to regulate epithelial tissue morphogenesis. Three objectives are planned and include: (1) testing how tissue structure is controlled by forces, (2) determining the cellular rearrangements that drive cell shape changes, and (3) studying how these changes affect tissue mechanics. The research will advance fundamental understanding of how mechanical factors couple with biological factors to build and shape living tissues, filling a gap in our understanding of the role that mechanics plays in translating genotype to phenotype during development. The research will utilize the model organism Drosophila melanogaster and combine biomechanical and confocal imaging studies with systematic optogenetic manipulation of cellular force generation and mechanics in order to determine how tension generated by cellular actomyosin contractility and adhesion mediated by E-cadherin at cell-cell contacts control epithelial tissue shape, structure, and mechanics during embryonic development.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
