Research Overview

"The progress of science requires the growth of understanding in both directions, downward from the whole to the parts and upward from the parts to the whole."

Freeman Dyson, The Scientist as Rebel

Bonds

Naturally occurring catalysis for bond formation (via enzymes) is highly proficient (fast rate coupled to high enantio-selectivity), environmentally benign, self-regenerative, and exquisitely regulated. No designed catalytic systems can claim all of these four hallmarks of “ideal” catalysis. We currently address the proficiency issue by pioneering trifunctional organocatalysis in model proton-transfer reactions (PTRs), in which mild catalytic motifs cooperative, on a chiral backbone, for asymmetric carbon-carbon bond formation that is fundamental in both designed and living systems.

Molecules

Enzymes are major drug targets, and their conformational flexibility is essential for finding isozyme-specific drug leads. Protein flexibility however is difficult to predict thus presenting considerable challenges for rational drug discovery. We currently use natural products as leads for generating new conformation-based diversity around existing functional epitopes to target new protein conformations for drug discovery by a combined experimental and computational approach that guides the iterative design/discovery cycle. 

 

Systems

Cells in multicellular organisms form communication networks in order to maintain tissue integrity and stability. One key question is how individual cells present compatible surface protein codes to help coordinate correctly differentiated states. We use chemical tools to capture surface proteins for proteomics analysis, followed by validation in human cell models. Understanding cell identity control by characterising signalling networks will enable development in cell reprogramming for tissue regeneration or repair.