This Faculty Early Career Development (CAREER) grant will investigate how mechanical and molecular factors interact to shape tissues during embryonic development. It will also show the interconnectedness of physics and biology to students from high school to graduate school. The small intestine is chosen for study because it must be packed into the body. This process is driven by mechanical forces, which will be studied. This work is important because it will expand our knowledge about tissue packing, which has relevance to human development. For example, improper packing of the intestine during embryonic development is linked to birth defects with limited cures. The research component of this award will help us understand 1) how molecular cues control mechanical forces that organize the small intestine, 2) how those forces in turn feed back on cell behavior, and 3) how variations in the mechanical process of shaping the small intestine helps distinct species meet their unique nutritional needs. This work will include a mix of experiments and mathematical models. There is also an educational component to this award. High-school juniors will have a week-long lesson about the connections between physiology, engineering, and developmental biology, with the small intestine as an example. High-performing high school students from disadvantaged backgrounds will learn about cloning and molecular biology, embryology, and biomechanics as part of Columbia University?s Hypothekids Hk Makers program. Graduate students will also learn, in class, about the biophysical aspects of tissue formation. Taken together, this award will provide a foundation from which the investigator's career will grow, integrating teaching and research throughout.
The long term goal of this award is to understand the profound physical transformation that occurs during vertebrate development, wherein a seemingly disorganized ball of stem cells is progressively sculpted into a precisely patterned complex organism. This must occur through the action of physical forces under genetic and molecular control; however, an integrated view of morphogenesis that accounts for both mechanics and molecular genetics is lacking. The work performed in this award will fill a portion of this gap by focusing on looping of the small intestine, a process driven by mechanical buckling of the initially straight intestinal tube. The underlying biological cues that control buckling during development remain elusive. This award combines mechanical testing, mathematical modeling, and retroviral gene misexpression in the developing chick embryo to study how bone morphogenic protein (BMP) signaling controls buckling morphogenesis in the small intestine, how forces generated during looping morphogenesis feedback on cell behaviors that drive buckling, and finally, how changes to genes controlling tissue mechanics underlie the emergence of morphological diversity across species.
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.
