We study life from the start.
Developmental biology has rich history of simply and carefully watching how embryos develop. We draw inspiration from the past and use new technologies of the future to study the processes involved in executing the blueprint encoded in the genome.
We work with the marine acoel worm, Hofstenia miamia, which allows us to collect zygotes and study development daily. While the genome consists of 950 million single base pairs, not all of that information is being used at all times. When do these different regions of the genome get activated to make complex mixture of muscle, neurons, and epidermis that we find in the adult animal? We use a combination of next-generation sequencing methods to interrogate these questions along with microscopy to visualize the instructions encoded in individual cells.
In organisms capable of regeneration, how stem cells retain their identity during development is an enduring mystery in biology. While many species have been used to investigate the role of stem cells in regeneration, most offer limited access to embryogenesis, leaving gaps in our understanding of when and how adult pluripotent stem cells form. Paul's postdoctoral research in the Srivastava Lab at Harvard utilized chromatin profiling data to explore regulatory mechanisms guiding differentiation during development and our group will continue to study the gene regulatory networks that underpin stem cell identity.
Technological advances in the isolation and sequencing of individual cells have made it possible to query the molecular profile of stem cells across the tree of life. In our group we use computational approaches to describe the molecular profile of Hofstenia stem cell populations and putative lineage-specific progenitors. We build gene regulatory networks (GRNs), a combination of cell-type specific transcription factors, for specification of various cell types. Studying the faithful differentiation of cells into in both development and regeneration will inform us broadly of how pluripotency and differentiation are regulated in stem cells.