Drug Discovery Innovation Group

G protein-coupled receptors (GPCRs) are the largest family of membrane proteins encoded by the human genome, and are vital for nearly all forms of life. GPCRs are located on the cell surface and allow cellular communication by transmitting extracellular stimulus into intracellular signals – this includes responding to external signals such as hormones, light, neurotransmitters, peptides etc. Upon receiving these signals, GPCRs activate an intracellular signal transduction pathway, leading to a cellular response. This is why GPCRs are so important: they are the gatekeepers that allow our bodies to respond to the environment and function properly. Consequently, GPCRs play major roles in almost all aspects of human physiology and are therefore implicated in a variety of disease states.

Our lab is focused in using multi-disciplinary approaches (including protein engineering, molecular pharmacology, and structural biology) to unravel important details about the molecular mechanisms underlying the action of GPCRs, and develop improved approaches for drugging these important therapeutic targets.

Nanobodies (Nbs) are small single-domain proteins that are only 1/10th the size of regular antibodies (IgGs), and are derived from heavy-chain only antibodies of found natively in camelids (camels/llamas/alpacas). Due to their small size, high stability, adaptability and ease of expression, nanobodies have become invaluable tools of scientific research for probing the function of a wide range of proteins.

There is immense interest in the use of nanobodies as potential therapeutic modalities particularly in diseases such as cancer and autoimmune disorders, with the first FDA-approved nanobody reaching the market in 2019. Our lab has developed novel approaches to help accelerate the identification of nanobodies against a variety of important biological targets.

Protein engineering is the process of designing or modifying proteins to create new or improved functionalities. This can involve altering the amino acid sequence, structure, or other properties of the protein to improve its activity, stability, or specificity.

Directed evolution is a protein engineering technique that involves generating and screening a large number of randomly mutated proteins to identify variants with improved properties. This is achieved by introducing random mutations into the gene encoding the protein, expressing the mutant proteins in a host organism, and then screening the resulting proteins for the desired function.

Protein engineering and directed evolution are valuable tools for drug discovery because they allow the design or discovery of proteins with specific properties that can be used to facilitate drug discovery efforts. Our lab is interested in developing novel protein engineering solutions to tackle difficult problems with drug discovery efforts at integral membrane proteins, in particular GPCRs.