Sammy Garcia, a senior biochemistry & molecular biology major at Dickinson College, developing a tool to link single-neuron transcriptomes to synaptic connectivity.
Both synapse and gene expression dysregulation underlies many CNS disorders. Understanding how neurons connect in a healthy individual, will help us understand what synapses are changed in disease. The Broad is an amazing place that provides you with the resources to leave an impactful mark in science. This experience has motivated me to pursue my PhD in the biological sciences.However, there is no technology to relate neuroanatomy to single-cell transcriptomes. We are building a new technology which enables the identification of individual synapses and their connections at a single-cell resolution. The foundation of this approach is an mRNA trafficking system that transports mRNA barcodes to pre-synapses. The trafficked mRNA barcodes are then read out with a spatial transcriptomics technique known as Slide-seq. To validate our system, we examined the projections from the ventral posteromedial nucleus (VPM) to various cortical targets by injecting an AAV carrying our trafficking system into this region of the brain. We then analyzed sections of the mouse brain to assess whether the constructs correctly traffic to synapses. Moreover, this data will give us valuable information about our system along with the VPM region.
Project: Developing a tool to link single-neuron transcriptomes to synaptic connectivity
Mentors: Dr. Mike Dolan and Judy Luu, Macosko Lab