Holistic measurement of diverse functional, anatomical, and molecular traits that span multiple levels, from molecules to cells to an entire system, remains a major challenge in biology. In this talk, I will introduce a series of technologies including CLARITY, SWITCH, MAP (Magnified Analysis of Proteome), and stochastic electrotransport that enable proteomic and structural imaging for scalable, integrated, high-dimensional phenotyping of both animal tissues and human clinical samples. SWITCH enables over twenty rounds of relabeling of a single tissue with precise co-registration of multiple datasets by synchronizing key chemical reactions in tissue processing. With SWITCH, we demonstrated combinatorial protein expression profiling and high-dimensional quantitative analysis of the human cortex. MAP enables scalable superresolution proteomic imaging of large scale tissues by expanding intact organs four fold linearly while preserving their 3D proteome, nanoscopic architecture, and intercellular connectivity. Using MAP, we demonstrated molecular imaging of subcellular architectures and accurate tracing of densely packed neural projections. To speed up the labeling process in CLARITY, SWITCH, and MAP, we developed a novel electrokinetic method termed stochastic electrotransport, which enables immunolabeling of whole mouse brains within 1-3 days. We hope these new technologies to accelerate the phase of discovery in a broad range of biomedical research.
Thesis Defense Seminar
Thesis Defense Seminar
With the accumulation of our knowledge about how memories are formed, retrieved, and updated, neuroscience is now reaching a point where discrete memories can be identified and manipulated at rapid timescales. Here, I will review recent advances in memory research that combine transgenic, optogenetic, in vivo imaging, and viral-tracing strategies to visualize and manipulate discrete sets of cells sufficient to modulate mnemonic processes. I will focus on three lines of research: acutely activating and visualizing hippocampus cells to drive the behavioral expression of positive and negative memories; acutely activating cells processing positive memories to suppress the return of fear; and, chronically activating cells processing positive and negative memories to enduringly modulate social and hedonic-like states. Together, I propose that defined sets of hippocampus cells provide a neuronal node sufficient to permanently alter healthy and maladaptive states