Nearly all multi-cellular organisms have mechanisms that allow specific tissues to withstand substantial mechanical stress without rupture or permanent deformation. These mechanisms often involve structures composed of extracellular matrix (ECM) proteins (e.g. elastin and fibrillin) that assemble into elastic fibers or elastic fiber-like structures that can stretch and flex but return to their original shape once force is removed. Information obtained from studies of elastic polymers found in nature has numerous potential applications in materials science, medicine and military projects (e.g. in tissue grafts, protective clothing and energy-absorbing soundproofing). The PI and co-workers have discovered novel elastic fiber-like structures in the nematode C. elegans that connect pharynx and adjacent muscle cells, and have named these structures nematode elastic fibers (NEFs). As the animals forage for food, NEFs stretch, bend, flex and pivot and help to position the pharynx in the center of the body cavity. In previous work, Dr. Vogel has identified two essential components of the NEF: the highly conserved ECM proteins hemicentin and fibulin-1D. These proteins co-assemble at NEFs and two other cell junctions that are also flexible and resistant to mechanical stress. The specific aims of the current proposal utilize the power of the C. elegans genetic system to: 1) dissect the mechanism of hemicentin and fibulin-1D assembly into NEFs and 2) determine the composition of these intriguing elastic polymers by identifying the other molecular NEF components. The long-term goals are to define the essential requirements for assembling NEFs, to assemble NEFs or NEF-like structures in vitro and a detailed analysis of the mechanical/biophysical properties of these intriguing structures.
The intellectual merit lies in the potential to provide detailed information into the assembly and composition of a novel type of cell junction. Although cell-cell and cell-ECM junctions have been the focus of intense investigation, hemicentin and fibulin-1D are unique in that they always assemble in a sandwich at junctions between cells (cell-ECM-cell) where they form a novel type of elastic and flexible biological glue.
There are two aspects of broader impacts that pertain to this project. One is the potential for societal benefit through the likelihood that the work will have relevance for materials science and bioengineering of synthetic biocompatible elastic materials that would be useful in a variety of applications. In addition to the potential utility of the research itself, another broader impact of the proposed research will be to utilize C. elegans as an ideal model organism to teach basic concepts in biology. In conjunction with the experimental goals of the research, molecular biology and genetics learning modules will be developed for UMBIs established, state-wide science education program. This program consists of three components that serve Maryland K-12 students: 1) UMBIs on-site teaching laboratory 2) Maryland Loaner Lab (MDLL) in which the necessary equipment and consumables are sent to teachers so they can enhance their lab offerings and integrate new curriculum in their classrooms and 3) a 32-station mobile teaching laboratory housed in a tractor trailer that travels throughput the state of Maryland to provide hands-on laboratory education for K-12 students. An additional benefit is that separate teacher professional development programs are available through all three components designed to provide teachers with an opportunity to expand their laboratory skills and enhance the content of their bioscience instruction.
