Tracing the origin and early evolution of animal cell type regulation with genomics and single-cell approaches
Cell types are the fundamental units of animal multicellularity. Distinct cell types are established and maintained by specific gene regulatory networks (GRNs), as well as epigenomic mechanisms that mediate the asymmetric access to genetic information within each cell. This cell regulation results in complex metazoan functions and structures. However, cell types and their regulation have only been characterized in a few species. Therefore, the origin and evolution of animal cell types remain largely unexplored, and so remains the evolution of the underlying GRNs and epigenomic mechanisms. 
In this project, we will develop a unified comparative framework to study cell type evolution and regulation from a multi-level and phylogenetic perspective. This project will focus on non-bilaterian metazoan lineages (Porifera, Ctenophora, Placozoa, and Cnidaria) as they are maximally informative towards reconstructing the evolutionary origins of metazoan genome regulation and of major cell types and their GRNs (e.g. neurons, secretory cells, stem cells, epithelial cells). To this end, we will integrate single-cell genomics and epigenomic profiling methods with advanced computational tools in order to: (1) investigate the origins of the animal regulatory genome; (2) characterize the diversity of cell type programs in non-bilaterian metazoans; and (3) model the structure and evolutionary dynamics of cell type-specific GRNs in these lineages. 
This evolutionary systems biology approach provides a complementary angle to both phylogenetically-restricted single-cell analyses and traditional cross-species studies based on targeted marker genes. Therefore, our results will fill a large gap of knowledge in our understanding of the origin and diversification of animal cell type programs and epigenomic mechanisms. In a broader context, this research program will provide unprecedented insights into the fundamental question of how cell types and their defining regulatory networks evolve.