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[Lecture] Leveraging the power of light microscopy and hydrogel-tissue chemistry to interrogate the brain across scales
Jan. 15, 2025
Speaker: Prof. Mojtaba R. Tavakoli

Time: 10:00-11:30 a.m., Jan 15, 2025, GMT+8

Venue: Rm. B117, Research Complex #2, PKU

Abstract: 

Light microscopy-based  (super resolution) technologies offer unprecedented opportunities to study biological systems as complex as the brain across scales, from the centimeter-sized whole organ down to its nanoscopic features. The advantage of fluorescence light microscopy, the molecular specificity and its broad accessibility, enables scientists across the Globe with a wide range of molecular tools to tailor experimental conditions for manipulating and interrogating cellular outputs, enabled by complex subcellular and molecular machineries. Cellular entities of the brain (neuron and glial  cells) are  physically wired  and form circuits, which together with  their molecular and functional characteristics enable the brain’s information-processing capability. Thus, a comprehensive understanding of the brain requires to study the brain at multiple levels, from the molecular machineries to the synapses, circuits and the behavior.

Multi-level investigation of the brain (e.g. molecular, cellular and circuit   levels) with light microscopy has been hampered by its limitation to provide structure contrast at the synapse-level. Hence, electron microscopy is the technology of choice to reconstruct the  brain circuit, as this technology provides a comprehensive structural contrast and nanoscale resolution. However, linking structural,  and functional characteristics of brain's cellular network to the intracellular compartments and their respective molecular machineries is extremely challenging with electron microscopy,  because sample preparation and readout are not usually compatible with direct visualization of specific molecules, requiring correlation with light microscopy.

In this talk, I will discuss our efforts on developing readily adoptable optical imaging and molecular tools enabling multi-modal investigation of the brain. We have developed the LICONN technology, for light microscopy-based connectomics, which combines the power of hydrogel-based expansion microscopy, optical imaging and automated reconstruction algorithm. Furthermore, I will discuss its application across species (human, rodent and fly), its current limitations and future prospects.

Source: College of Future Technology, PKU