(3ct) Enabling Technologies for High-Throughput Whole Tissue Analysis At Single-Cellular Resolution: From Model Organisms to Human Organs

Understanding complex biological systems require integrated structural and molecular information. However, current techniques fall far short of providing complete system-relevant information with both global scope and molecular resolution. To address these limitations, I have developed two unique sets of technologies that enable rapid extraction of structural and molecular information at single-cellular resolution for broad biological systems.  For small model organisms, such as C. elegans and Drosophila melanogaster embryos, I developed novel microfluidic technologies that allow precise and rapid manipulation of a large number of samples for imaging, screening, and laser ablation of single cells. These technologies have been used to study nervous system of C. elegans and embryogenesis of Drosophila melanogaster embryos. For large mammalian tissues, such as mouse brain and human tumor tissues, I have developed a novel technology that enables whole tissue imaging and molecular phenotyping without prohibitively inefficient mechanical sectioning and reconstruction. I have applied this technique to understanding function and dysfunction of mammalian brains. In conclusion, these enabling technologies promise to provide high-content system-wide structural and molecular information that may enable integrative understanding of a broad range of biological systems.