Mechanisms of Protein Protection by Desiccation-tolerance Molecules

University Of North Carolina At Chapel Hill, Chapel Hill NC

Investigators

Abstract

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Gary J. Pielak from the University of North Carolina at Chapel Hill to investigate mechanisms of protein protection used by large and small desiccation tolerance molecules. Organisms selected to survive desiccation do so by making protective molecules, but the mechanisms of protection are mostly unknown. From a practical perspective, understanding dehydration protection will improve biomanufacturing processes and bio-based products, such as biologic drugs and industrial enzymes. These studies will provide graduate and undergraduate students with specialized training in protein chemistry and physical biochemistry, which are useful skills for basic and industrial research. The four main ideas proposed to explain desiccation protection — water retention, vitrification, water replacement and molecular shield hypotheses — will be tested by using a combination of protein engineering, nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy and rheometry. The most common natural protective small molecule is the nonreducing disaccharide, trehalose, but there are also several classes of protective disordered proteins. The most well-studied members are the Late Embryogenesis Abundant (LEA) proteins, which were discovered in plants but are also found in animals. The most recently discovered class of protective proteins — Cytosolic Abundant Heat Soluble (CAHS) proteins — are unique to tardigrades. CAHS proteins are remarkable not only because they protect other proteins and enzymes but also because they form protective gels. This project will compare and contrast each of these types of protective molecules to better understand how their structures contribute to the survival of organisms under dehydrating conditions. 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.