Principles of cell fate specification
In the Askary lab, we strive to find simple principles that are used during embryonic development to make complex tissues like the mammalian retina. To this aim, we develop innovative tools to monitor, characterize, and manipulate cells. We leverage both our methods and our findings to make better therapeutic strategies and molecular diagnostics, with a focus on neurodegenerative disorders of the eye.
Identity and pattern of the cells are influenced by their intrinsic states, extrinsic signals, and stochastic processes. Collecting quantitative data is the first step to understand how these factors work together to make a functional nervous system and how they go wrong in developmental and degenerative disorders. We have developed a method for sensitive and scalable in situ readout of DNA barcodes (Askary et al., 2020 Nature Biotechnology). Now our team is using this technology, together with CRISPR base editors, to monitor the intensity and order of signals that cells receive over time. We also map gene expression in the retinal neurons and progenitors using spatial transcriptomics. To find interesting patterns in these data, that can lead us to principles of cell fate determination, we use computational tools of systems biology. We believe new technologies and interdisciplinary approaches are essential for providing new insight into the oldest questions in developmental biology.