Membrane trafficking at atomic resolution

My group is interested in understanding the fundamental cellular process of intracellular protein sorting in human neuronal cells. Specifically, we study protein machineries that operate as cargo vans within the cell. These protein complexes direct the cargo (cell surface receptors) either to recycling or degradative sorting routes, which is central to proteostasis. Defects in these protein machineries result in abnormal trafficking of cell surface receptors, that has implications in several neurodegenerative diseases, including Parkinson’s and amyotrophic lateral sclerosis (ALS).

We take advantage of hybrid structural biology approaches to obtain an overall three-dimensional map of these trafficking protein complexes. We also employ X-ray crystallography, Electron microscopy and NMR in combination with biophysical, biochemical and molecular biology methods to decipher how these protein assemblies engage their cargo. Our group uses multidisciplinary approaches and together with cell biology collaborators we construct atomic resolution maps of cellular sorting events that are critical in our understanding of membrane trafficking pathways at both molecular and systemic scale.

Traineeships, honours and PhD projects include:

• Structural and functional characterization of Commander complex
• Characterisation of COMMD family proteins and their role in endosomal recycling
• Molecular understanding of the role of retriever complex in intracellular trafficking of cell surface receptors
• Towards understanding the assembly of SMCR8-C9orf72-WDR41 holo complex and its implications in frontotemporal dementia
• Molecular characterisation of proteins involved in ALS