My general research goal is to engineer molecular probes and to develop new photonic techniques to enable biological discovery. We apply a combination of approaches including molecular design and engineering, imaging, chemical synthesis, molecular and cellular biology.
My current research is focused on two areas:
(1) Develop photonic probes for biological applications.
(2) Study the regulation and function of gap junction coupling in C elegans.
(1) Develop photonic probes for biological applications.
Caged probes
Photoactivatable or “caged” molecules are powerful probes for studying molecular dynamics with pinpoint accuracy. Because the intensity, duration, shape and direction of a light beam can be manipulated at our will, photoactivation (uncaging) offers superb accuracy and flexibility in controlling cellular biochemistry.
We are engineering new caged probes by exploring new concepts in caging chemistry, aiming to produce compounds suitable for in vivo applications, such as mapping neural circuitry, controlling cellular signaling, and regulating gene expression.
Imaging probes
The superb sensitivity of fluorescence detection has enabled its broad application in biological imaging. We are developing new fluorescent sensors for monitoring cellular metabolic activities, focusing on processes pertaining to insulin release in beta cells.
In parallel, we are also developing new magnetic resonance imaging (MRI) contrast agents to follow physiological processes in living animals. Recent advances in MRI instrumentation and pulse sequence design have made it possible to achieve cellular resolution, providing a truly non-invasive imaging technique to diagnose optically opaque organisms at the molecular and cellular level.
(2) Physiological regulation and function of gap junction coupling
Intercellular communication through gap junction channels is wide spread in multicellular organisms and is essential for many vital physiological processes. We are interested in understanding the functions of gap junction coupling during development, currently using the nematode C elegans as a model because it has a very limited number of cells, invariant cell lineage and favorable optical properties for imaging.
Using a newly developed imaging technique (Trojan-LAMP), we find that patterns of junctional communication undergo a dynamic remodeling in developing C elegans embryos. We are investigating the mechanisms that regulate cell coupling strength which lead to the formation of distinct communication compartments during development. In parallel, to better understand the function of dynamic cell junctional communication, we are developing specific pharmacological reagents to modulate cell coupling.