Grant: Discovery Grants Program - Individual

Protein self-assembly plays many essential roles in nature and presents new opportunities to develop biomaterials. One family of self-assembling proteins are hydrophobins, which are small globular proteins produced by filamentous fungi to modify their environment. Secreted hydrophobins behave like detergents and can change shape to form rodlets, which are an extremely durable and water repellent coating over aerial hyphae and spores. The unusual biochemical properties of hydrophobins have generated interest in developing them for commercial applications as emulsifiers, foam stabilizers and as an agent to protect and modify surfaces. Currently a comprehensive, molecular-based understanding of the properties of hydrophobins and how they form rodlets is lacking. Only a handful of high-resolution structures for hydrophobins exist, but these are for hydrophobins so diverse in sequence and structure that it is difficult to correlate the sequence and structural properties of these hydrophobins with their function. In collaboration with Dr. Emma Master (UofT) I have begun to characterize the structure and function of a new sub-class of hydrophobins. By studying these hydrophobins I will correlate sequence features of hydrophobins with their functional properties. Specifically, the objectives of this proposal are to: 1. Characterize the structure and function of diverse hydrophobins and determine what factors influence their properties. 2. Determine how rodlet formation occurs and build a working model of the rodlet structure. 3. Design hydrophobins that assemble into rodlets with desired properties.To address these objectives I will use an experimental approach combining molecular biology, structural biology, and biophysics. This work will contribute to our knowledge of protein self-assembly and will provide a mechanistic understanding of hydrophobin properties and function that is critical to engineer them for commercial applications. My research program will allow trainees to develop skills in molecular biology, nuclear magnetic resonance spectroscopy, X-ray crystallography, circular dichroism spectropolarimetry, atomic force microscopy, and electron microscopy. These diverse skills and and experience working with a protein that is currently being developed for commercialization will ensure the success of highly qualified personnel in their future careers in the biotechnology, pharmaceutical and academic sectors.