Tight junctions are multiprotein complexes in cells that control the permeability of ions and small molecules between cells, an essential feature in multicellular organisms. However, recent evidence suggests that tight junctions are not always tight, and small molecules and ions can pass in between cells. Yet, how this "loosening" of the tight junction barrier is achieved is not well understood. In this project, the investigator will use a combination of computation and experiment to examine how the structure of tight junctions influences their function. The PI will integrate her research into outreach and undergraduate education by focusing on three major activities: (1) the PI will design and develop a new course series specifically designed to apply physics to biological topics, (2) she will partner with the Museum of Science and Industry in Chicago to engage high school students and expose them to research careers in science, and (3) will partner with the Oak Park Education Foundation to develop one-day hands-on workshops for kids age 8-11 on the 'biology of the cell'. She will continue working with the UIC PAP-STEM program to recruit high-achieving UIC undergraduate students from under-represented groups into her research group.
Proteins known as claudins are one of the major components of tight junctions that control its permeability to ions and small molecules. Little is known about the assembly and organization of claudins into networks of tight junction strands that surround the cell and the architecture of claudin pores. In this project, computational investigations will be performed to study the paracellular transport as a function of tight junction architecture and molecular permeability of claudin pores. Atomic scale molecular dynamics simulations will be combined with Brownian dynamics calculations to study (1) molecular basis of claudin pore gating and selectivity, (2) claudin assembly and tight junction architecture, and (3) to develop a global model for paracellular transport across tight junctions. The results of computational modeling will be validated by in vitro measurements of claudin function and mutational studies, which in turn will be used to refine the atomic model of tight junctions.
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.
