Developing Technology to Study Complex Biological Systems

The ensemble behavior of biological systems, such as tissues and organs or microbial communities, is governed by the molecular profile of individual biological components as well as their interaction with each other and the environment. For instance, organ systems comprise multiple types of cells, interacting with each other and the environment to drive complex functions and behaviors. Recent advances in sequencing or antibody-based assays has enabled the molecular profiling of individual cells but intercellular interactions and the functional architecture of cells remain elusive. Understanding the functional network of cells is especially important to understand brain functions and dysfunctions as well as cancer development. To tackle these difficult questions, we innovate imaging, sequencing, and sensing technologies that enables high throughput, high resolution profiling of biological systems and to identify molecular and cellular interactions in tissues. We closely work with neurobiologists, cancer biologists, and computational biologists to unveil how brains process social interactions and identify inter-cellular regulatory networks that are affected during disease.

Virus evolution and infection is another focus of our research. Due to their high mutation rate, short life cycle, and selection pressures, viruses exist as heterogeneous, dynamic populations. Although a detailed genomic profile of individual virus greatly informs the infectivity and pathogenesis of the ensemble population, single virus genome sequencing as not been achieved due to the tiny amount of genomic materials in a single virus particle. We are pioneering a single virus genomics platform for high throughput, unbiased sequencing of individual virus genomes. Single virus genomics will open a wide avenue for new investigations in virus infection and evolution. We closely work with field virologists to obtain virus samples from wildlife animals and to design a widely applicable sequencing platform.

We enable new biological studies by developing analytical tools. Leveraging our extensive expertise in material chemistry, nanotechnology, optics, and microfluidics, we enable in depth analysis of biological substances with high-resolution and with minimal disruption of the native biological context. The followings are the drives of technological innovation in our lab: 

Single Molecule Bioimaging

High resolution imaging allows the spatial context of cells and the spatial organization of cellular and molecular networks to be probed. We have been developing a high throughput, single molecule-resolution imaging platform to simultaneously image a large number of RNA, DNA, and protein species. Using the new platform, we aim to extract underlying molecular interactions as well as intercellular regulatory networks. We also have been developing live imaging technologies to monitor cell movements and interaction with other cells in vivo. 

microscope with cells

Quantum Dot Probes for Bioimaging

Single molecule imaging or single cell tracking in vivo requires high quality fluorescent probes that are bright, photo-stable, and compact. The probes also need to have narrow emission profiles (color purity) for sensitive multi-color imaging. Semiconductor nanocrystals, known as quantum dots (QDs), have unique optical and electronic properties that make them ideal for this application. We are developing new synthetic methods to prepare high quality QDs that emit in the visible to near-infrared. We engineer both the inorganic and organic components of QDs to optimize interaction and transport in complex biological systems. 

Quantum dots

Droplet Microfluidics 

Droplet microfluidics offers unmatched advantages for high throughput assays on single cells, viruses, and even molecules. Using pico-liter drops as individual reaction vessels, drop microfluics ensures high reaction efficiencies even with minimal input material, providing single molecule sensitivity. After performing massively parallelized assays, individual drops can be screened one-by-one and the drops containing the desired products can be selected using a microfluidic-sorter. Drops can also be used as templates for polymerization reactions of enclosed substances, generating highly monodisperse products with a defined structure. We are developing new microfluidic modules and platforms to enable new biological measurements and ultra-sensitive assays. We also seek to understand the fluid dynamics inside microfluidic channels to enable precise control of drops and cells. 



Students in our lab will have the opportunity to learn: Nanocrystal synthesis, ligand engineering, droplet microfluidics, spectroscopic and analytical characterization, cellular imaging, single cell/virus genomics and transcriptomics, cell culture techniques, and molecular biology