Uncovering Molecular Mechanisms of Biological Processes at the Single-Molecule Level

The Youngkwang Lee group applies advanced imaging and spectroscopic techniques to solve important problems in cell signaling and develop novel biosensing platforms. We use research methods from multiple disciplines — biophysics, biochemistry, materials science, nanotechnology, and optics. We integrate these tools into our research program to quantitatively analyze biomolecular reactions at single-molecule resolution. The research program in the lab has two main areas of interest described below.

Molecular Mechanisms of Cell Signaling At Membrane Surfaces

Many of cellular processes involve a series of biochemical reactions that take place on membranes. The importance of membrane reactions is underscored by the fact that more than 50% of current drugs target membrane proteins and many of cytosolic proteins are fully functional only within membrane environments. Reactions on membrane surfaces are intrinsically different from those in solution. Proteins experience enhanced local concentrations, orientational and conformational change, restricted diffusion, and physical assembly with their interacting partners; as a result, many emergent properties arise at the membrane. A major focus in the lab is to elucidate molecular mechanisms regulating the activation of Raf kinases, which are involved in various cellular processes with biomedical significance. We seek to understand how molecular assembly processes spanning multiple length scales define spatiotemporal activity of Raf kinases and other associated enzymes. A relative lack of methodology for quantitatively analyzing membrane processes effectively hinders an understanding of this process. We solve this challenge by adapting a synthetic model cell membrane platform. A key idea is to reconstitute signaling reactions on a supported lipid bilayer (SLB) in a highly controlled manner. A suite of cutting-edge single-molecule fluorescence imaging and spectroscopic techniques are employed to quantitatively elucidate detailed molecular mechanisms. Our approach is generally applicable to other systems, beyond membrane signaling. Overall, we apply chemical and physical principles to understand complex biological phenomena, seeking to leverage our discovery to develop better therapeutic strategies.

Functional Nanostructure/Biomolecule Hybrids for Novel Bioassays

Quantification of extremely low-abundance biomolecules (e.g. nucleic acids and protein) is of tremendous importance for applications such as early diagnosis, adjuvant therapy, food safety monitoring, and biological warfare defense. We aim to develop novel optical sensors by synthesizing functional nanostructure/biomolecule hybrids. Our primary synthetic building blocks include plasmonic nanoparticles, artificial cell membranes, DNA nanomachines and recombinant proteins. The ultimate detection sensitivity of the hybrid sensing system is at the single molecule/particle level.

Perspective Students

Students working in my lab will be trained to be skillful at a variety of biochemical and biophysical techniques that include in vitro reconstitution, enzymatic assays, chemical modeling, molecular cloning, protein purification/modification, microfabrication, coding-based high-throughput data analysis, advanced optical imaging and spectroscopy, and so on. If you want to learn more about research in my lab, please contact prof. Youngkwang Lee via email. We are always looking for graduate and undergraduate students in pursuit of excellence in science!