The formation of functional tissue architectures during embryonic development depends on the ability of cells to orchestrate collective tissue-level movements. The goal of my research program is to understand how cells work together to collectively generate the shape and structure of multicellular tissues in the process of morphogenesis. Our current understanding of morphogenesis has been limited by conceptual and technological barriers to dissecting the mechanical and molecular inputs that together coordinate cell behaviors. During this award, we will address these challenges and focus on resolving several key gaps in our understanding by: (1) elucidating how contractile and adhesive protein machineries in cells help coordinate activities between neighboring cells to give rise to collective cell and tissue movements and (2) dissecting how mechanical inputs integrate with molecular inputs to coordinate cell behaviors within tissues. Using the model organism Drosophila melanogaster, we are taking innovative approaches to address these questions in the context of epithelial tissue morphogenesis. To enable us to dissect mechanisms that coordinate cell behaviors, we are developing and using new technologies for controlling and quantifying the cell machineries and forces that drive these cell behaviors. These techniques, in combination with quantitative modeling, will allow us to dissect the molecular and mechanical mechanisms that coordinate cell behaviors within multicellular tissues. This work will provide a foundation for integrating mechanics into our understanding of how genetic and biochemical factors control development and may motivate new strategies for controlling tissue shape and structure in vivo and in vitro. More broadly, the tools and framework we develop will enable us to investigate the mechanisms that coordinate cell behaviors in a broad range of multicellular processes. A better understanding of the mechanisms underlying collective cell behaviors can elucidate general principles of self-organization in biological systems, provide insight into how improper regulation of these processes leads to human disease, and develop new approaches to manipulate these processes for therapeutic benefit.
Functional tissues and organs are generated during embryonic development by the movements and behaviors of cells. The work we propose will greatly enhance our understanding of how individual cell behaviors are coordinated to help generate complex tissue structure. Because the basic cell biological mechanisms are highly conserved from flies to humans, this work will shed light on how improper regulation of these processes results in disease states such as birth defects and cancer and may enable new therapeutic strategies.
