Imaging at the genomic-scale: from 3D organization of the genome to cell atlas of the brain

Prof. Xiaowei Zhuang, the 2019 Robert Hofstadter Memorial Lecturer and the David B. Arnold Professor of Science, Professor of Chemistry and Chemical Biology and Professor of Physics of Harvard University, will give the Appied Physics/Physics colloquium.

Inside a biological cell, thousands to tens of thousands of different genes function collectively to give rise to cellular behavior. Understanding the emergent behaviors of cells require imaging at the genomic scale. Such genomic, transcriptomic and proteomic analyses of single cells promise to transform our understanding in many areas of biology, such as regulation of gene expression, development of cell fate, and organization of distinct cell types in complex tissues. We developed a genomic-scale imaging method, MERFISH, which uses combinatorial imaging to massively multiplex single-molecule measurements and error-robust barcoding to minimize measurement error. Using this approach, we have imaged RNAs of hundreds to thousands of genes in individual cells. By enabling single-cell transcriptomic analysis in the native context of cells and tissues, MERFISH facilitates the delineation of gene regulatory networks, the mapping of molecular distributions inside cells, and the mapping of distinct cell types in complex tissues. We have also extended this approach to image numerous genomic loci and trace the 3D structure of chromosomes in single cells. In this talk, I will describe the technology development of MERFISH and its applications focusing on generating the cell atlas of complex tissues and mapping the 3D organization of the genome.