Our research is among the most rapidly evolving topics of biophysics that combines the traditional quantitative strengths of physics with clear potential for biological application and health impact. We take highly interdisciplinary approach integrating quantitative imaging, biotechnology, soft condensed matter, and living cells to explore exciting unknowns in biophysics. Here are some examples of what we are working on.
1. Protein phase separation
1. Protein phase separation
A cancer-causing protein spontaneously forms granules in living cells. Turning on or off granules can turn on or off cancer signaling.
It’s recently shown that certain proteins spontaneously form micron-sized high-concentration granules and low-concentration surroundings in living cells, reminiscent of phase separation in physics. We found the physical state of granule nucleation or dissolution can promote or inhibit diseases such as cancer. We follow individual protein granules with high spatiotemporal resolution and combine data-mining of entire human proteome and high-throughput imaging to understand the biophysics of protein granules such as the driving force for protein phase separation, nucleation kinetics, and the mesoscale structure through self-assembly.
2. Quantitative imaging of living cell
2. Quantitative imaging of living cell
CRISPR gene-editing and quantitative imaging show how a group of human cells respond to hostile environment such as cold temperature.
Like people with different personalities, we are interested in the heterogeneity exhibited by individual cells in a cell population. It’s increasingly recognized that the heterogeneity is not merely noise but may underlie cell fate decision, drug resistance in cancer, and many other important biological processes. To gain insights, we use powerful imaging platform such as high-through quantitative imaging and CRISPR gene-editing for native protein tagging in living human cells. These technologies also enable us to track dynamic non-equilibrium processes in living cells, cell-cell communication, and cell-materials interaction.
3. Single-molecule dynamics of biomaterials
3. Single-molecule dynamics of biomaterials
A bio-polymer chain navigates through obstacles (unlabeled background) in intermittent stretch-recoil steps, contrary to expectation of continuous snaking-through.
Decades of theories of underlying dynamic processes in soft condensed matter and biomaterials have been mostly built on ensemble-averaged measurements. We recently show that direct high-throughput imaging at single-molecule level often yield surprises and shed new lights, contrary to classical expectation. For example, we show that a long polymer chain driven through obstacles would walk in discrete stretch-recoil steps rather than continuous smooth snaking-though as commonly thought. Even simple hard-sphere colloid suspension can exhibit break-down of classical Gaussian displacement distribution.