Engineering Biochemical Systems

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I am particularly interested in pursuing curiosity-driven ideas at the intersection of engineering, chemistry and biology. We ask the “what if?” questions in research to find innovative solutions that will impact Canada's society and economy. In Engineering Biochemical Systems, I propose to harness the power of proteins with both transformative strategies for controlled release and pioneering 3D cell culture designs to guide cell fate. Affinity release is typically controlled by native interactions, but this method is inherently limited and typically not tunable. We invented a tunable protein release strategy (published in Science), but this requires fusion protein expression. We now propose an entirely new system to identify specific binding partners for each protein of interest and immobilize these partners on a new hydrogel delivery vehicle, resulting in an affinity release system based on specific orthogonal interactions. With this system, we anticipate delivering multiple proteins at different rates, simultaneously, and propose to develop the mathematical model to predict and optimize release. Controlling protein release from polymeric nano/microparticles is limited by the process itself to very small amounts of protein released and poor bioactivity. By taking advantage of electrostatic interactions, we invented un-encapsulated protein release of positively charged proteins from negatively charged nanoparticles (published in Science Advances). We now propose a platform strategy using transient display of charge to control release using zwitterionic polymers and mathematical modelling to understand and predict release. Mimicking the cellular microenvironment is key to understanding cell fate, which is inherently limited by conventional 2-D culture. We invented a series of hydrogel chemistry strategies that provide us with the tools required to ask key questions in cell biology. We propose to synthesize novel 3D hydrogels with defined biochemical and mechanical properties, including transient protein gradients, to better understand how the extracellular matrix influences cell invasion, growth and fate. With systems that differentiate between healthy and cancer cells, we have the opportunity to investigate strategies that specifically inhibit invasion. Graduate students and post-doctoral fellows will advance knowledge and gain valuable experience in fields of critical importance to Canada's innovation economy: polymer chemistry, synthetic biology, protein release, computational modeling, engineering design. Equity, diversity and inclusion in HQP are the cornerstone of my laboratory. I have pursued and maintained ethnic diversity and equal numbers of women and men throughout my entire career. Herein, HQP will learn to think creatively and independently through specific programs and organizational structures that I have designed. Their experience in my laboratory will be enriched through multi-disciplinary collaborations worldwide.