Research

We study biological systems through the lens of physical chemists.

ITK_mGL_4-Scale-time.avi

Receptor Tyrosine Kinase (here, ITK in T cells) form these bright clusters, condensates, upon T cell landing onto the artificial lipid bilayer.

Biomolecular Condensates in Cells

Did you know that there are protein-rich liquid droplets (sometimes, gels or solid aggregates), formed by phase transitions of biomolecules? They are known to organize other biomolecules in cells. Those droplets are called biomolecular condensates, a new class of cellular compartments.

In recent years, biomolecular condensation has emerged in various biological processes including gene regulation and cellular signaling. These condensates are proposed as a compelling mechanism for cells to organize and control biochemical reaction networks. However, mechanistic understanding of how their distinct physical properties and phase transition dynamics translate into biological functions remains largely unexplored.

Therefore, we ask this central question:

How do phase transition dynamics and mechanisms regulate biochemical reaction networks at molecular level in biology?

Bridging Biology

and Soft Materials

Our research is at the intersection of traditional physical chemistry and emerging biological questions. We apply principles of statistical mechanics, thermodynamics, soft matter physics, and chemical kinetics—foundational to physical chemistry—to understand the behavior of biomolecular condensates, a new class of cellular compartments.

Projects

The central idea is to discover new biology enabled by protein phase transition condensation in biological processes, such as RNA equilibria or signal transduction, and apply it to develop a new synthetic system.

Project 1. Synthetic Biomolecular Condensates with Controlled Physico-chemical Processes

Can specific molecular interactions tune phase transition dynamics and condensate properties in non-equilibrium condition?

Project 2. Tyrosine Kinase Phase Transition Dynamics in Cell Signaling

Whether/how does different phase transition mechanisms and dynamics connect to their roles in biology?

Project 3. High-throughput micro-condition droplets for phase-transition dynamic studies

Can we develop high-throughput platform for wide range of micro-conditions for screening different phase transition mechanisms and dynamics?

Systems and Tools

1. Liquid-liquid Phase Separation (LLPS, Coacervates)

We utilize coacervates—polymer-rich droplets formed via liquid-liquid phase separation (LLPS)—as an experimental model for biomolecular condensates. While coacervates are ubiquitous in daily life, appearing in almost everything from cosmetics and food to underwater adhesives and ink, our lab is pushing the boundaries of their composition and functions.

2. Peptide/DNA/RNA Chemistry

Moving beyond traditional synthetic polymers, we specialize in developing coacervates composed of polypeptides and oligonucleotides. Our research investigates how these droplets behave under diverse experimental conditions, with a particular focus on engineering them for advanced functionalities, such as the compartmentalization and storage of biomolecules.

3. Quatitative Microscopy Tools and Live Cell Imaging

We leverage quantitative fluorescence imaging, including single-molecule microscopy, to elucidate the phase transition nucleation mechanism. This approach provides an unexplored window into the dynamics of protein condensation during immune signaling, revealing stochastic nucleation behaviors that remain obscured in traditional ensemble measurements.

Beyond nucleation, our lab applies these quantitative tools to investigate the transport and partitioning phenomena of guest molecules within multiphasic coacervates. By bridging molecular-scale dynamics with macroscopic behavior, we aim to understand how biological systems harness phase transitions to spatially and temporally organize complex reaction networks.

4. Supported-lipid Bilayer Imaging Platforms

We synthesize supported-lipid bilayers (SLBs) as artificial membrane systems that can be precisely functionalized with a wide array of biomolecules. Our lab utilizes SLBs as a single-molecule level imaging platform to study how live cells interact with biological membranes in real-time. In addition to live cell imaging, we can leverage SLBs to characterize the enzyme kinetics of membrane-bound or recruited proteins within a controlled environment. By mimicking the native cellular interface, our SLB platforms offer immense potential for developing next-generation biomolecular sensors, biocompatible coatings, and advanced bioanalytical tools.

Broader Impact

We will establish a novel framework for applying physical chemistry to living systems, addressing the emerging questions in biology. My research program has the potential to provide new insights into RNA biology and cellular signaling and may offer novel platforms for high-throughput drug screening and molecular medicine.

Understand the fundamental rules of life

Develop high-throughput experiment platforms

Lead to design novel platforms for molecular medicine

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