Surface Bioconjugation for Regenerative Medicine and Biosensing Applications

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A number of recent major inroads in biochemistry, cellular biology and medicine have helped improve our understanding of the molecular mechanisms governing cell growth and differentiation, assuring tissue regeneration after injury or causing abnormal cell proliferation leading to cancer. This research has underscored the importance of the extracellular matrix (a network of non-living tissue outside the cell that acts as a reservoir of specific proteins), which plays an active role in modulating intercellular communication. During the last decade, research aiming to mimic this unique environment for therapeutic applications has shown great promise; our fight against cancer has also greatly improved thanks to the design of new therapies based on monoclonal antibodies. However, challenges associated with therapeutic angiogenesis for tissue repair and regeneration, as well as with optimized antibody production for the clinic, still remain. Keeping these needs in mind, the central objective of this NSERC Discovery Grant Research Program is to understand how the modulation of the dynamics of the interactions between proteins may be utilized to control their biological activity, and thereby affect cell behaviour and biological outcomes. This will be achieved by focusing on the characterization of tethered molecules to be utilized as molecular sensors and modulators. While inherently versatile, the tools to be developed will be adapted to meet the challenges of two applications of interest: (i) the development of tuneable surfaces and scaffolds allowing for the control of protein display in a spatial (orientation, density, localization), temporal (controlled release) and multifactorial (combination of cues) fashion and (ii) the design of new tools to tackle the glycosylation of monoclonal antibodies and related receptors. These systems will be of great interest for the design of in vitro cellular models and in tissue engineering applications such as therapeutic angiogenesis as well as to establish quantitative structure-activity relationships by designing artefact-free assays. The design of new purification approaches to isolate a monoclonal antibody bearing the best therapeutic potential will also be investigated. The knowledge and know-how we will generate about these fundamental issues have the potential to profoundly impact the biomedical and biopharmaceutical industries. Furthermore, throughout this Research Program we will train outstanding students at the interface between engineering, biochemistry and biophysics. These students will acquire fundamental knowledge and technical skills highly sought after by biomedical and biopharmaceutical companies.