Organelles are specialized compartments within the cell, in which proteins are selectively imported to work cooperatively to conduct a variety of cellular functions. Although many organelles were discovered decades ago and found to play essential roles for the cell, questions regarding to which extent protein complexes cooperate within and between organelles remain completely elusive. One of the major obstacles in characterizing organellar interactomes is that these proteins are often membrane-embedded/associated, generally highly organized in the three-dimensional space, and thus recalcitrant to purification by standard procedures. Therefore, in many cases, only the most stable ‘core’ complexes can be studied by classical structural biology approaches.
To overcome these limitations, our group studies the structural interactome of proteins in their organellular environment using our newly developed cross-linking mass spectrometry approach. We focus on two organelles, the endoplasmic reticulum and mitochondria, the functions of which are linked to a wide variety of physiological/pathological conditions. A comprehensive map of the structural interactomes of these organelles will provide crucial insights into the interaction patterns, the binding interfaces, and the three-dimensional organization of protein complexes and supercomplexes. Functional studies are also performed to further characterize newly discovered protein interactions and networks.
In addition, we are interested in exploring synaptic protein interaction networks with subcompartmental specificity, defining interactomes of the presynaptic active zone, synaptic vesicles (SVs), endosomes and the postsynaptic density (PSD). Since different compartments contribute to the precision of neuronal signaling and to synaptic plasticity, these studies are instrumental for understanding synaptic function, its adaptations to different types of stimuli and, ultimately, the molecular basis of memory and learning.
In both biological avenues, we combine the structural interatomic information with complementary approaches from structural biology, molecular biology, cell biology, neuroscience and informatics, to gain a more detailed understanding of how protein assemblies are arranged and co-operated in different biological