The research in our lab focuses on quantitatively understanding mechanisms of complex biological processes at multiple spatial and temporal scales. There are three major directions: 1) the mechanism of activated conformational dynamics of proteins; 2) the mechanism of assembly dynamics of microtubules and how they are controlled in different cellular processes; 3) automated methods for quantitative analysis of live-cell imaging data.

1. Mechanism of protein conformational dynamics from an energy-flow perspective.

Conformational dynamics are essential for the functionality of protein molecules. Functionally important conformational changes are activated processes in which a protein molecule needs to surmount a free energy barrier. The rigorous and quantitative physical mechanism of activated dynamics in highly conjugated systems with highly heterogeneous interactions, such as protein molecules, is an unsolved and fascinating question. We recently developed a scheme for analyzing energy flows during a conformational change that have shed new lights on the underlying physical picture. The gist is that energy flows from degrees of freedom (DoFs) with fast time scales into DoFs with slow time scales, so that energy accumulates in the slow DoFs and enables them to cross energy barriers significantly higher than thermal energy to achieve the target conformational change. The slow DoFs are the reaction coordinates that govern the progress of an activated process.

2. Assembly dynamics of microtubules.

Microtubules are a major component of the cytoskeleton and play essential roles in many essential cellular processes such as mitosis, morphogenesis, polarization, etc. The key to microtubule’s functionality is their assembly dynamics, which allows the entire cellular microtubule network to promptly disassemble, reassemble and reorganize for different processes. The physical mechanism of microtubule assembly dynamics is a fascinating question central to our understanding of functionality of microtubules in vitro and in vivo. In living cells, a wide array of regulatory proteins, collectively called microtubule associated proteins (MAPs), tightly control the fine details of microtubule assembly dynamics. Together they form efficient cellular machinery in which microtubules are the infrastructure while MAPs are the fine-tuning gadgets. We use kinetic simulations to investigate both the detailed physical mechanism of microtubule assembly dynamics and how they are controlled and tuned by interaction-networks of MAPs in different cellular processes.

3. Automated methods for tracking microtubules in live-cell imaging data.

The dominant experimental tool for investigating behaviors of microtubules in living cells is fluorescence microscopy. The imaging data collected from such experiments contain invaluable information on the dynamics and morphology of microtubules in different cellular processes and environments. Tracking fluorescently labeled microtubules from such imaging data is essential for quantifying microtubule dynamics in cells. This is currently done by manual tracking, which is extremely labor-intensive and often subjected to subtle human bias and errors. We developed an efficient algorithm for accurate and automated tracking of microtubules in live cell fluorescent imaging data. Information extracted from tracking provides invaluable inputs to our modeling efforts.