A specific set of metabolic pathways allows organisms to grow and reproduce, maintain compartments and structures, and respond to environments. Metabolic pathways cover a wide range of enzyme activities from "classical" anabolic and catabolic reactions of metabolites, to "novel" regulatory roles in signaling pathways and organelle biogenesis. Understanding this delicate metabolic network might offer novel therapeutic intervention in oncology, inherited metabolic disorders, inflammation and degenerative diseases.
The SGC MOB group investigates human metabolism from three different perspectives.
1. High throughput structural biology for metabolic enzymes & complexes
With a repertoire to date of >150 structures of metabolic enzymes (50 of which are linked with genetic diseases), we aim to understand structure-function relationships, delineate enzyme mechanisms, and deorphanize new genes.
2. Understanding Inborn Errors of Metabolism (IEM)
A subset of our target proteins are linked with inherited monogenic disorders (Inborn Errors of Metabolism). We adopt an open-access model to share our reagents and data in a protein-centric platform with geneticists, clinicians, patient groups and drug developers.
3. Small molecule inhibitors/activators for metabolic disorders
We develop a collaborative programme ('Target Enabling Packages, TEP') for novel drug discovery, to identify small molecule starting point for stabilizing misfolded/aggregated proteins (pharmacological chaperones), or reducing the accumulation of toxic metabolites or down-regulating gain-of-function (inhibitors).