Biological Projects

Defining the structural interactomes of organelles, synapses, cells, and viruses

Proteins in all biological systems are highly organized in three-dimensional space, forming membrane-enclosed or membraneless compartments, signaling pathways, dynamic assemblies, and stable complexes. Many of these structures are only viable in their native environment, making them recalcitrant to traditional biochemical characterization.

Proteome-wide XL-MS offers the opportunity to capture the interactions and spatial arrangement of proteins without having to extract them from their complex biological system. Our group utilizes this technology to study the structural protein interactome of mitochondria, whole cells, and virus particles. In addition, we are interested in exploring synaptic protein interaction networks with subcompartmental specificity, defining interactomes of the presynaptic active zone, synaptic vesicles, endosomes and the postsynaptic density. These studies are instrumental for understanding synaptic plasticity and function, its adaptation to different types of stimuli and, ultimately, the molecular basis of memory and learning.

We generate comprehensive maps of the protein localizations and structural interactomes within these biological structures. These findings inform functional follow-up studies to further characterize the newly discovered protein structures, interactions, and spatially resolved networks, using approaches from structural biology, molecular biology, cell biology, neuroscience, and informatics.