The research interest of our group lies at the interface of biology, chemistry, and physics.
We have recently discovered that, in single cells, signaling and gene expression events occur in a surprisingly burst-like fashion.
With quantitative single cell time-lapse fluorescence microscopy, we uncovered a previously unknown frequency-modulated (FM) mode of control in signaling, where signaling proteins are coherently phosphorylated and de-phosphorylated in pulses within a single cell, and the frequency and duration of pulses are modulated by external signal.
Observations of new modes of regulation provide the impetus to ask a broad range of scientific questions and develop new spectroscopic tools to visualize chemical dynamics in single cell.
Elucidate the mechanisms of FM pulses. How do they happen? Are there general mechanisms linking bursting signaling pathways? We will use genetic perturbations and light-controlled protein-protein interaction systems to dissect the network and model their dynamics.
Examine crosstalk and integration. Given that many signaling pathways pulse and propagate to downstream genes, we will investigate in depth how bursting in diverse signaling pathways overlaps temporally to crosstalk and integrate at the transcription factor and the promoter levels.
Single molecule signaling dynamics. How do we visualize phosphorylation reactions in individual cells? We will use single molecule techniques to track interactions between kinases (or phosphatases) and their target proteins to explore epigenetic and gene expression events.
Explore signaling in multi-cellular organisms. What roles do signaling dynamics play in developmental cell fate decisions? In particular, does nutrient starvation result in dynamics in zebrafish similar to the FM bursts observed in homologous pathway in yeast? And what is their relevance to disease and aging?
