Experimental and Modeling Study of the Optical Properties, Heat and Cold Tolerance, and UV-Resistance of the Eye Lens Crystallins

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Nontechnical: This award by the Biomaterials Program in the Division of Materials Research to University of California Irvine is for developing a scientific understanding of how nature produces transparent, durable biomaterials, as exemplified by the proteins making up the eye lens. Although the molecular details of these proteins vary among different organisms, they are functionally similar in their high stability and resistance to temperature extremes and UV-light damage. Understanding the structural factors diverse lens proteins have in common will help guide the design of future temperature and UV-resistant biomimetic materials. The educational plan includes training of students at the Ph.D. and undergraduate levels. These students will be trained not only in the specific skills needed to complete the research, but also in thinking and problem-solving across disciplinary boundaries. Another important component is outreach to middle school and high school students. The goal of the outreach program is to increase interest in science as a career among middle school students and includes a variety of activities and visits to the PI's labs. Technical: This project seeks to understand the molecular basis of protein stability, in particular resistance to extreme temperatures and UV light exposure. Studies of extremely stable structural proteins that are not homologous but play the same functional role will provide insight into sequence determinants of stability without interference from effects that are conserved due to enzymatic activity in thermostable enzymes. The particular proteins chosen for this effort are eye lens crystallins from three organisms adapted to extreme environments. The box jellyfish (Tripedalia cystophora) J2-crystallin has a high thermal stability, while the gamma-S1- and gamma-S2-crystallins from the Antarctic toothfish (Dissostichus mawsoni) help confer unusual cold tolerance on the eye lens of this organism. The iota-crystallin of the diurnal gecko Lygodactylus picturatus, has an unusual UV protection mechanism involving binding of a retinol derivative. NMR and optical spectroscopic studies coupled with molecular dynamics and Monte Carlo simulations will elucidate the important structural factors and intermolecular interactions that confer high stability on these proteins, guiding the future design of biomimetic materials. The educational plan includes training of students at the Ph.D. and undergraduate levels, who will be exposed to a broad range of experimental and computational techniques, as well as the continuation of a successful outreach program aimed at middle school students.