Grant: Discovery Grants Program - Individual

Fibres, nanoparticles, films, sponges and hydrogels formed by proteins are essential for biological survival and have outstanding biotechnology potential. My NSERC-funded research program focuses on spider silk proteins, with long-term objectives of (1) providing fundamental insight into protein supramolecular assembly and (2) enabling rational engineering of proteins with specific properties. In terms of protein engineering, this may be further subdivided into modulation of properties that affect the final self-assembled material and/or one or more steps along the pathway the protein takes to achieve that form. Orb-weaving spiders produce up to seven protein-based silks, each with a distinctive survival function and correspondingly different requisite mechanical behaviour. We focus on spider silks that are relatively "understudied", with aciniform (or wrapping) and pyriform silks targeted, to date. In all cases, my program targets a fundamental understanding of the atomic-level structuring, dynamics, and features of a given silk in its soluble storage state, in the final self-assembled state (e.g., fibre, film, nanoparticle, sponge etc.), as well as in intermediates that form en route from storage to assembly. This is enabled by biophysical and materials property characterization of disparate states of these protein-based materials. We develop and optimize approaches to ensure consistent outcomes from protein self-assembly and also apply our knowledge of atomic-level structuring to engineer new functionality and behaviour into silk proteins. Three major aims are targeted over the next five years: i)Expand our toolkit of silk materials through continued development of a comprehensive understanding of structure-property relationships in a wider range of these enigmatic proteins ii)Develop and investigate recombinant silk-based composite materials, including self-assembled structures formed by mixtures containing multiple silk types, fusion proteins comprising disparate silk units, and new ways of processing silk fibres. iii) Functionalize silks using rationally engineered fusion proteins and through site-specific incorporation of nanoparticles and evaluate the resulting changes in mechanics, environmental responsiveness, optical properties, and ability to load these materials with cargo molecules Beyond the scientific and technical aims that are targeted, this Discovery Grant will allow highly qualified personnel from the undergraduate student through to the postdoctoral level to become expert in: (1) application of biotechnology approaches for protein production and processing; (2) characterization of proteins in soluble states, nanoparticles, films, fibres etc. at levels from the atomic-scale through to the functional perspective; (3) applying creativity in an informed manner to develop new approaches to self-assemble proteins; and, (4) rational engineering of proteins, enabled through structural biology and computational biochemistry.