Research Projects

PROJECT SUMMARY Dynamic changes in the spatiotemporal patterning of transcription factor binding on cis-regulatory DNA elements drives the developmental transition of cell lineages during neurogenesis. In the human brain, neurons are generated from early embryonic development until early postnatal stages. The main neurogenic region in the adult brain is the dentate gyrus in the hippocampus. While adult hippocampal neurogenesis has been confirmed in the majority of mammals, it is unclear if this phenomenon exists in the human brain.

Project Summary (Abstract) Gaining a comprehensive understanding of brain-wide cellular organization in the human brain has long been recognized as a critical foundation for understanding complex brain functions, including who we are as humans. In this project we propose to take on this challenge and establish a pipeline capable of imaging the entire human brain at cellular resolution.

Cell Type-specific Anterograde Circuit Mapping and Functional Control by Optimizing YFV-17D Transneuronal Systems Summary To elucidate the functional organization of brain circuitry we need to delineate neuronal connectivity and control the activity of neurons with specific connectivity. Both tasks have increasingly relied on transneuronal viral vectors. Anterograde transneuronal viral vectors, which spread from presynaptic neurons to the postsynaptic neurons, can reveal the neuronal projections and selectively target postsynaptic neurons.

PROJECT SUMMARY Identifying how neurons are connected to each other in the brain is an important and necessary step towards understanding how brain activity gives rise to behavior, and how it is perturbed by disease. Unfortunately, currently available methods have limitations that make it challenging to visualize these brain wiring diagrams. In addition, there is an urgent need for a method that will make it possible not only to unveil brain connectivity, but also to genetically modify the functional properties of neurons connected in a circuit.

Project Summary Cell signaling pathways in the brain are an essential part of a complex system regulating the activity and coordination of neuronal networks.

Project Summary The quest to understand the brain’s complex structure has become more challenging as the high degree of molecular heterogeneity among brain cells has become evident in recent years. Mapping the brain in detail will require incorporating large amounts of molecular information into high-resolution imaging. Current imaging methods are limited by the number of distinguishable detection channels, so greater degrees of multiplexing entail repeated cycles of stripping and reapplying probes.

PROJECT SUMMARY Brain function depends on forming and maintaining synaptic connections between neurons of specific types, yet systematic descriptions of cell-type connectivity and the molecules that instruct these relationships remain challenging because we lack some necessary tools. Traditional approaches for measuring synaptic connections and networks – such as whole-cell electrophysiology and anatomical reconstructions – sample only a few cells or small tissue volumes, do not readily scale to many animals or genotypes, and do not ascertain the molecular type and state of each cell.

PROJECT SUMMARY Single-cell technologies have revolutionized the characterization of mammalian brains allowing unbiased census of cell types and their transcriptomic and epigenomics signatures. However, the mapping of molecular signatures onto three-dimensional brain structures remains highly challenging since most single-cell methods can only analyze disassociated cells or nuclei. We propose to develop photonic-indexing sequencing (pi-seq) strategies for in situ spatial barcoding with single-cell resolution.

PROJECT SUMMARY A detailed and comprehensive census of central nervous system (CNS) cell types and states is essential to our understanding of the neural substrates of cognition and behavior.

Project abstract BRAIN pioneers are people who take on significant risk as participants in first-in-human or early neurotechnology studies for the sake of helping to further science.