(3ej) Revolutionizing Systems Biology Experimental Methods with Integrated Micro-Systems

Systems biology takes a holistic approach to investigations into complex biological systems and studies the interactions and dynamics of cellular and molecular components in a living organism. This comprehensive approach will lead to a deeper understanding of many fundamental biological processes, such as gene functions and neurodevelopment. In other words, with advanced studies on heterogeneous system-level dynamics among individual organisms, we can pinpoint the complex underlying mechanisms of critical medical challenges in the modern society, such as aging and neurodegenerative diseases, and hence develop personalized therapeutic strategies. One of the critical experimental challenges for researchers in systems biology is to collect individual-specific multi-dimensional data of complex systems. They need to develop generalizable experimental paradigms which enable (1) high-throughput screening and precise perturbation of complex biological systems on the individual level, and (2) simultaneous extraction of individual-specific, multi-scale biological information ranging from molecular level to organismal level.

To address this challenge, I have developed new experimental strategies by creating the integrated micro-systems with nematode C. elegans, an excellent model organism for systems biology. First, I have designed an open-accessible and programmable microfluidic platform. By exploiting capillary-driven contact line dynamics on this platform, I have invented a generalizable sample handling method to achieve high-throughput and yet ultra-simple screening and on-demand perturbation of complex living organisms. Second, I have also engineered an integrated microfluidic / ionic circuit system that consists of two units: the fluidic circuit unit which allows for parallel characterization of individual-specific cellular phenotypes, and the ionic circuit unit that offers rapid in situ concentration and fractionation of nucleic acid-based molecular probes, and successfully achieves multiplexed profiling of tissue-specific gene expression patterns in whole animals. I have applied the integrated micro-systems into the study of key questions in neuroscience, such as the underlying mechanism of stress-induced or age-related behavioral decline through tissue-specific transcriptional regulations. The integrated micro-systems I have designed require only minimum equipment and simple operation, and hence can be easily adopted by a broader community of systems biology researchers.

My future research will continue to advance experimental methods in systems biology with innovative engineered solutions. I will combine these integrated micro-systems and multi-omic techniques such as next-generation sequencing, to develop new experimental pipelines to uncover individual-specific, tissue-specific transcriptomic and proteomic signatures which determine the organismal level phenotypes and behaviors. I will also utilize these micro-systems in other complex biological systems, such as human tissues and organoids. I envision these new system-level experimental strategies to play a critical role in understanding neurological diseases and eventually revolutionizing therapeutic strategies.

Teaching Interests:

My teaching philosophy is to ignite the students’ passion for learning and understanding engineering fundamentals, to cultivate their critical thinking ability, and to help them transform the fundamental knowledge into unique and practical skillsets. As a graduate instructor and teaching assistant, I have taught core undergraduate Chemical Engineering courses including “Numerical Methods in Chemical Engineering” and “Science of Engineering Materials”. As a co-instructor and guest lecturer, I have taught advanced graduate Chemical Engineering courses including “Microfluidics and Biological Applications” and “Non-Equilibrium Electrokinetics”. I am interested in teaching core Chemical Engineering courses such as “Transport Phenomena”, “Mathematical Methods for Engineers”, “Fluid Mechanics”, “Separation Process” and “Thermodynamics”. I will also design advanced and specialized courses such as “Microfluidics and Applications”, “Electrokinetics and Applications”, “Micro and Nano Fabrications”, and “BioMEMS”.