NSF Award
2303857
Cell migration is required for animals, including humans, to develop normally and is essential for functions including immune response and wound healing. This process is highly conserved and controlled by various signals that direct cells to move to the correct places. However, it is not understood how these cues from the cell’s environment are changed in complex and dynamic tissues as they develop. It is known that migratory cells behave differently in different contexts, but not known how those cells interpret physical cues versus chemical cues or how they integrate these sets of information. This project takes advantages of interdisciplinary approaches combining the well-characterized cell biology and genetics of fruit flies and mathematical modeling. These systems will be used to ask how chemical and physical cues are combined to result in accurate cell migration. This research will be complemented with ongoing, strategic efforts to broaden and improve research training and biology education. This includes efforts to mentor and train undergraduate and graduate students in research, analysis, and interpretation; expand participation of historically underrepresented individuals in scientific careers; strengthen the quantitative reasoning skills of undergraduates, as part of the NSF-Improving Undergraduate Science Education (IUSE) initiative, in large classes; improve upper-level courses and research training through implementation of best-practices in pedagogy and mentoring; and partner with scientific community outreach programs. Thus, the project will advance our understanding of developmental biology while providing cutting-edge education and new opportunities for people interested in science. <br/><br/>This project utilizes molecular, genetic, imaging and modeling approaches to examine how cells interpret a combination of physical and chemical information to migrate correctly. It is not well understood how cells sense small differences in concentrations of chemical cues to orient themselves in a chemoattractant gradient, or how this signaling works accurately as tissues grow and remodel. In addition, how cells mechanistically respond to the physical characteristics of the substrates along which they move is not well established. Moreover, the impact that physical structure has on chemical cue distribution in a heterogenous tissue is not well characterized. In cases when clusters of cells move together, it is also unclear how they communicate spatial information to each other as they move. This work will address these questions through the characterization of a cluster of motile cells, called border cells, that migrate between germline cells in response to receptor tyrosine kinase signaling during Drosophila oogenesis. This research aims aim to identify the relationship between changes in the migratory behavior of border cells and the varied physical structures they encounter while moving through the egg chamber; determine the distribution of active chemoattractants in egg chambers and the physical and chemical components that govern this pattern; and uncover the dynamics of guidance receptor signaling within a motile cell cluster that mediate concentration-dependent migratory behaviors. The results will provide insight into general mechanisms of developmental signaling, directed cell motility, and coordinated changes of cell behaviors in vivo.<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.
