Chemical and biological processes studied with advanced imaging techniques

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Our research program centres on the development of fluorescence-based methodologies to study chemical and biological systems, and on the application of the fundamental knowledge gained using these methods to generate novel materials and diagnostics. We are able to synthesize customized fluorescent probes with desirable chemical reactivity and photophysical behaviour, and to then develop and exploit state-of-the-art single molecule fluorescence imaging methodologies with them, in our pursuit of the mechanistic underpinning of complex systems. Fundamental to our research work is our ability to monitor single molecules in action. The field of single molecule spectroscopy has evolved from its original focus on the study of biophysical phenomena, to mechanistic exploration of reactions in heterogeneous media, both on the surface and within a diverse range of nanocomposite materials/catalysts. Most tantalizing are recent breakthroughs in the imaging of biological systems and characterization of catalysts at work with “super resolution” (beyond diffraction limit) and sensitivity. These techniques exploit the induction/enhancement of fluorescence upon a chemical reaction (fluorogenic compounds) to visualize, map and ultimately understand what occurs at the microscopic and nanoscopic (a billionth of a meter) level. The techniques are however mostly limited to a subset of fluorogenic probes that are photochemically triggered (they are physical spectators - beacons). Tremendous opportunities exist to interrogate biological systems and nanomaterials upon careful design of fluorogenic compounds that respond to reactive chemical species of interest (active players “chemical flares”). In the coming grant period we will capitalize on our progress of the past 6 years and on recent developments in the field of super resolution imaging working on 3 interrelated contemporary problems. (I) We will design and prepare fluorogenic probes to monitor the redox status of lipid membranes and also fluorogenic electrophilic probes to trigger reactions akin to those observed with by-products of lipid peroxidation. Our goal is to establish the relationship between the chemistry of reactive oxygen species (ROS) and their biology. (II) We will visualize, map and study key redox processes both in biological systems and nanomaterials implementing our newly developed probes, combining SMS and incorporating super resolution imaging strategies. (III) We will develop new SMS strategies to explore the structure and the assembly dynamics of supramolecular structures/nanomaterials tuning conditions for high yields and improved quality materials. Our goal in this case is to gain key mechanistic information and translate it to the manufacture of better nanomaterials when applicable. In general, we will gain knowledge on the photochemistry/photophysics of new compounds. We will develop molecules that have functions that many researchers seek. The chemoselective probes and imaging methodologies will enable fundamental transforming discoveries of broad impact on cell function and activity correlated with ROS production. The probes and imaging methods will also pave the way to prepare improved nanomaterials/supramolecular structures. New imaging technologies to be developed will become the standards of quality and structural characterization in nanoscience. Our program will provide landmark examples where unique approaches are explored and cutting-edge imaging technologies are developed toward understanding chemical and biological systems.