Research Summary

We focus on developing various physical and chemical approaches to study biological processes in neurons. Currently, there are three major research directions: (1) Investigating the axonal transport process using optical imaging, magnetic and optical trapping, and microfluidic platform; (2) Developing vertical nanopillar-based electric and optic sensors for sensitive detection of biological functions; (3) Using optogentic approach to investigate the temporal and spatial control of intracellular signaling pathways.

(1) Vesicle transport in axons

In neurons, the axon acts as a conduit for organized transport of materials between the cell body and the synapse, a process that is essential for the function and survival of neurons.  The extreme lengths and narrow calibers of axons, along with the large amount of materials that must be transported through axons represent unique challenges for neurons.  Defective axonal transport, such as accumulation of axonal cargoes and slower transport rate, has been linked with a range of neurodegenerative diseases.  We are investigating molecular mechanism associated with retrograde axonal transport of neurotrophins and how molecular motors and various regulatory proteins coordinate this essential process.  We are also developing a novel technique that permits external manipulation of axonal transport via magnetic and optical forces.  The capability to manipulate axonal transport affords new approaches to investigate the linkage between defective axonal transport and neuronal degeneration.

 

(2) At the nano-bio interface: probing live cells with nanosensors

The rapidly evolving field of nanotechnology creates new frontiers for biological sciences.  Recently, we and other groups show that vertical nanopillars protruding from a flat surface support cell survival and can be used as subcellular sensors to probe biological processes in live cells.  We are exploring nanopillars as electric sensor, optical sensors, and structural probes. In particular, we find that nanopillar electrode protruding from the flat surface significantly enhances the cell membrane-electrode coupling by deforming the plasma membrane inwards. Interestingly, the presence of high membrane curvature induces accumulation of proteins around nanopillars and affects certain biological processes. The interplay between biological cells and nano-sized electrode is an essential consideration for future development of interfacing devices.

 

(3) Optic control of intracellular signaling pathways

Cells are constantly processing environmental cues such as growth factors to make decisions on cell fate, e.g. survival, proliferation, differentiation, migration, and apoptosis.  To ensure proper conversion of a specific environmental input into a distinct cellular output, the activation of intracellular signaling pathways is tightly regulated in space and time.  Compared with our understanding of protein players involved in various signaling pathways, much less is understood about how these temporal and spatial aspects affect cell behavior, largely due to the lack of effective tools to precisely regulate signaling pathways in space and time. We use light-gated protein-protein interaction systems to control the activation and inactivation of intracellular signaling pathways. The ability to control signaling pathways by light offers unprecedented precision in temporal and spatial dimensions.