Cellular behavior depends on the activities of countless individual biomolecules. Compared to population-based methods, the ability to simultaneously perturb and analyze individual molecules provides a more direct and quantitative understanding, and unprecedented insights, of how these molecules function. I am passionate about adapting and developing new single molecule tools to investigate important but currently inaccessible molecular and cellular biology questions and achieve more predictive cellular manipulation.
More specifically, my developed image-based tools have provided an exquisitely detailed view of RNA regulation both in vitro and in a cellular context. By combining methods from Astrophysics and deep-learning, I achieved to investigate ‘in situ’ splicing activity as a function to nuclear spatial organization in individual mammalian cells, and revealed a surprisingly new functional role of splicing regulation, working as a gene expression filter in an ‘economy of scale’ manner. I further explored the RNA/DNA regulation at the molecular level. By overcoming the technical challenges (e.g. high resolution <1nm, fast dynamics ~ seconds, and high stochasticity) using magnetic tweezers, I achieved to monitor nucleic acid base-pair competition dynamics in real time and invented a 4th generation sequencing technique (which led to a successful biotech startup Depixus@).
In future, I plan to combine my research experiences in molecular and cellular RNA regulation using diverse single molecule tools. I will establish a lab that focus on quantitative single molecule RNA biology, emerging from basic single-cell research to tool developments for RNA-based therapies.