NSF Award
2217560
The development of animals from a single cell to adulthood is a complex operation requiring extreme coordination of billions of molecular events. Remarkably, development of most animal species occurs normally despite radical changes that may occur in the environment that would individually impact these molecular reactions. This property suggests that evolution has selected for and can encode gene regulatory networks that generate similar developmental outcomes despite changing conditions. This proposal aims to understand how animals can maintain the correct timing of gene expression when developing at different temperatures. Specifically, the investigators have developed tools to directly measure how and when animals turn on and off key developmental genes. They will use this system to dissect how changes in global gene expression are maintained across different cells and tissues during development at variable temperatures. This will allow the investigators to determine the unknown architectures of gene expression that are in place to make sure development in varying environments generates similar outcomes. As part of this project they will also provide research experiences for an undergraduate student, and they will perform outreach to minority-serving high schools in New York City.<br/><br/>Temperature impacts all biochemical reactions. For multicellular developmental systems, temperature fluctuations pose particular challenges because the orderly morphological progression depends on both spatially and temporally coordinated cellular decisions. It has been shown that overall developmental rates of poikilothermic animals obey Arrhenius scaling, though scaling parameters are genus and even species dependent. Despite the myriad diverse chemical reactions involved, this temperature scaling is uniform, leaving the relative timing of key developmental milestones unchanged. It remains unknown how this is achieved and, more generally, how individual molecular decisions that control developmental processes are buffered against temperature and synchronized within and across tissues to maintain developmental precision. The goal of this project is to uncover the organizational strategy and molecular mechanisms that confer this robustness. The investigators have developed a unique microfluidics methodology that allows high-resolution imaging of gene expression in multiple C. elegans larvae simultaneously throughout post-embryonic development. This technology will enable the investigators to determine how transcriptional patterns of key regulatory molecules are organized at different temperatures and enable them to model how Gene Regulatory Networks (GRNs) that generate these patterns work. The studies put the investigators in a position to now pioneer quantitative in-vivo studies of the temporal patterning GRN.<br/><br/>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.
