Talk Title: Protein-based tools for studying brain signaling and neurodegenerative diseases

Abstract: One major challenge in neuroscience is capturing and manipulating neuronal signaling and modulation with high spatiotemporal resolution and across a large brain volume. To address this gap, my research group takes a chemical biology approach to design novel classes of protein-based sensors and tools. For example, we have designed new classes of fluorescence-integrators which generate permanent marks upon detection of specific neuromodulators. These fluorescence-integrators will enable whole-brain mapping of opioids, epinephrine, dopamine, and other neuromodulators with high spatial resolution. We have also designed light- and chemical-activated protein switches for controlling the activity of peptide agonists for G protein-coupled receptors (GPCRs), which will enable the activation of GPCRs in selective neuronal circuits to study their causal-effect on various physiological processes and behaviors. These protein-based sensors and tools will significantly facilitate the study of brain signaling and neuromodulation. Another significant hurdle in neuroscience is the lack of reagents to target misfolded a-synuclein (a-syn) protein aggregates, a hallmark of synucleinopathies. We have designed a-syn fibril-selective nanobodies which show efficacy in inhibiting pathology development in cultured neurons and mouse models. The a-syn fibril-selective nanobodies will provide valuable tools for studying synucleinopathies.