The primitive streak is the "organizing center" for a fundamental process in early development of reptiles, birds, and mammals called gastrulation. During gastrulation cells from the outside of the embryo travel inward through the embryo, itself, which eventually leads to the formation of the internal organs. Without the evolutionary advent of gastrulation, the animal form might still be stuck at the flatworm stage. Gastrulation depends on a critical process known as epithelial-to-mesenchymal transition, which represents a fundamental switch in cell behavior from preferring a cohesive interconnected state between individual cells to one in which cells prefer to move about independently. It turns out that this switch, which is normal and healthy during early development, can be devastating to humans when it turns on again in the case of some malignant tumors. Indeed, this is the switch that is one of the primary causes of cancer spreading known as metastasis. It is now known that this switch is also one of the primary drivers of fibrotic disease processes. The objective of this project is to study the biophysical mechanisms underlying the switch during gastrulation using the bird embryo as a model system. Our overall hypothesis is that localized upregulation of actomyosin contractility is a required driving force that underlies maintenance of the primitive streak during gastrulation and is critical for the cellular switch. To better understand the specific role of actomyosin contractility in these processes, the investigators will use a combination of high-resolution time-lapse microscopy, quantitative bioengineering analyses, and biochemical/molecular perturbations. The long-term goal of the research is to understand how mechanical forces regulate and control this switch, and to use this knowledge to treat diseases, such as cancer and fibrosis, as well as to construct and shape living tissues de novo that can be used for applications in tissue engineering.
Broader Impacts This project will result in the advanced training of undergraduate and graduate researchers with unique analytical skills based on a multi-disciplinary, integrative approach involving experimental and theoretical aspects of cell and developmental biology and engineering. Students from underrepresented groups will be recruited to participate in the research program. GIFT (Georgia Internships for Teachers) brings teachers from all over metro Atlanta to work during the summer in science and engineering labs at Georgia Tech, so that they may gain a better understanding of scientific research and develop innovative lesson plans to bring with them back to their classrooms. As part of an ongoing partnership with the GIFT program, the investigators have developed a cohesive, hands-on curriculum, which conforms to Georgia state teaching standards, and is designed to teach broad principles of biology to high school students. The educational component of this project will make a significant impact not only on the students and teachers who are directly involved, but successful implementation of the plan will involve disseminating the curriculum to the wider metro Atlanta area, and eventually, statewide throughout Georgia.
