My laboratory has a dual focus – the development of high-end imaging and synaptic physiology. All of our projects make use of super-resolution imaging techniques, including stimulated emission depletion microscopy (STED) and ground state depletion microscopy followed by individual molecule return (GSDIM). We combine these techniques with conventional imaging, electron microscopy, quantitative biochemistry, and imaging mass spectrometry, including nanoscale secondary ion mass spectrometry (NanoSIMS). The ultimate goal of our work is to understand the functional organization of the cell: the connection between the topological distribution of cellular elements (proteins or organelles) and their function. We focus on the synapse, whose relative simplicity and well understood function render such structure-function studies more feasible.

 

At the same time, we have a strong interest in using advanced microscopy techniques, and in developing new imaging probes, and new ways of applying them. We are especially interested in the development of new fluorescence labeling methods, ranging from novel affinity probes (aptamers, nanobodies) to new lipid probes and to the genetically-encoded incorporation of non-canonical amino acids in target proteins (click chemistry). We have recently applied these probes to NanoSIMS imaging, using what we termed correlated optical and isotopic nanoscopy (COIN). Moreover, click chemistry enables the mass spectrometry imaging of genetically encoded targets, using a novel technique that we termed specific protein isotopic and fluorescence labeling (SPILL).

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