This project aims to provide insights into cell-to-cell communication that play a crucial role in forming tissues and organs and the organization of different body parts during embryonic development. How cells communicate and govern these fundamental biological processes are highly complex and dynamic, and their behavior is very difficult to predict from knowledge of the individual parts. Therefore, the question arises how we should analyze and understand such complexity and which measurement technologies will prove most useful. Recently, several high-throughput approaches for collecting large-scale datasets, particularly those involving gene expression, have unlocked the door to data-driven systems biology-based projects. However, studying many interactions, even in a closely interconnected network, is powerful, but it is often hard to see the forest for the trees. Most often, system biologists rely on mathematical and computational models to analyze large-scale datasets and use these models to make scientific breakthroughs. To inspire and train the next generation of scientists in both experimental and computational approaches, this project will provide an opportunity for undergraduate students from diverse backgrounds to learn both cutting-edge cell biology-based experimentation and computational methods for formulating, simplifying, and extracting critical information from large-scale quantitative experimental data. A combination of hands-on training and lesson plans on the concept of 'cellular decision-making' for high school teachers will further promote data-driven biology among high school students. The graduate students and postdoctoral fellows working on this project will integrate experimental and mathematical modeling techniques that can be applied to broad areas of biology. This quantitative research theme will be carried forward by mentorship to high school students and through public engagement activities with the local community.
The epithelial-mesenchymal transition (EMT) is a central mechanism for diversifying the cells found in complex tissues. During EMT, epithelial cells adopt mesenchymal properties by altering their morphology, cellular architecture, adhesion, and migratory capacity. Several growth factors, including TGF-beta and Wnt, have been shown to trigger the EMT in both embryonic development as well as normal and transformed cells. However, a mechanistic and integrated understanding of how these various factors cooperate to induce the EMT in epithelial cells or transdifferentiation in fibroblast is still lacking. The goal of this project is to develop an integrated understanding of how Wnt and TGF-beta pathways control fundamental cell biological and developmental processes of EMT and cell migration. The research project will reveal mechanistic insights into how Wnt signaling drives EMT and promotes cell migration, and determine whether cooperation between Wnt and TGF-beta signaling is necessary for EMT. The project will also provide a biochemical portrait to determine how proteins in the Wnt pathway interact and interconnect with TGF-beta signaling and determine how these connections change as epithelial cells undergo transdifferentiation.
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.
