(3jz) Robust and Programmable Microbial Systems for Sustainable Biomanufacturing and Living Therapeutics

Microorganisms hold immense potential for solving pressing environmental and health-related challenges. Through metabolic engineering and synthetic biology, we can reprogram microbes to combat climate change, valorize waste, and produce important chemicals and materials sustainably. However, different microbes are naturally suited to perform different metabolic tasks and trying to engineer a single strain to do everything can be inefficient or unstable. Thus, one powerful approach is to use microbial consortia, which enable division of labor, allowing different species to specialize in distinct tasks, improving efficiency and reducing the metabolic burden on individual strains. They also offer enhanced stability and adaptability in dynamic environments through synergistic interactions and resource sharing. Yet only a limited number of microbial species have been engineered, leaving much of Earth’s microbial diversity—and its functional potential—underutilized. Even worse is that, among the engineered microbes, prokaryotes account for the vast majority, which further reduced the potential of microbial consortia.

My lab will focus on engineering probiotic yeast–probiotic bacteria consortia as robust and programmable microbial systems. Probiotic strains are especially compelling as chassis because they are generally regarded as safe (GRAS), exhibit long-standing compatibility with the human microbiome, and can survive and function in harsh physiological and industrial environments, such as low pH, oxidative stress, or antibiotic exposure. These properties make them ideal candidates not only for health-related applications but also for sustainable biomanufacturing in non-sterile, large-scale systems. Compared to traditional bacteria–bacteria consortia, cross-kingdom systems combining probiotic yeasts (e.g., Saccharomyces boulardii, Issatchenkia orientalis) and bacteria (e.g., E. coli Nissle 1917, Lactobacillus spp.) offer enhanced metabolic diversity, reduced competition, and broader environmental adaptability. By taking the advantage of both prokaryotes and eukaryotes, I aim to enable microbial communities that can perform even more complex biosynthetic functions, colonize and interact with host environments, and maintain stability across time and space. Three key initiatives will be performed to achieve the research scope.

1. Discovery and engineering of host-independent DNA replication, transcription, and translation machinery

• Develop cell-free systems for DNA replication, transcription and translation, respectively, and assemble them to fully reconstitute the central dogma in vitro
• Transform the above in vitro system into an in vivo system to establish a host-independent system for facile engineering of probiotic yeasts and bacteria

2. Machine learning guided discovery of genetic elements for cross-kingdom gene expression.

• Leverage transcriptomic data from microbes from different kingdoms as a database to design promoter, RBS and terminator that could be used cross different kingdoms
• Implement designed genetic elements to the host-independent system for cross-kingdom microbial engineering

3. Applications in sustainable bioproduction and microbiome-based therapeutics

• Engineer synthetic yeast–bacteria consortia for sustainable biosynthesis of value-added chemicals through division of labor and co-culture optimization.
• Design programmable inter-species communication systems to enable coordinated therapeutic functions in microbiome-inspired consortia.

Research experience

During my doctoral studies, my research work centered around engineering different E. coli strains for various applications, including biosensing, CO₂ assimilation, chemical productions, and protein engineering. Besides, I developed a host-independent transcription system via T7 polymerase in various prokaryotes. During doctoral study, I also learned and studied a cell-free protein synthesis system. My postdoctoral work included the development of novel genetic tools, such as landing pad systems for multi-copy gene integration, and metabolic engineering of a non-model yeast, Issatchenkia orientalis, for organic acid production. The combination of my research experience on engineering both prokaryotes and yeasts has equipped me with essential skills to achieve my research goals.

Teaching interest

With a strong foundation in chemical engineering, as well as extensive research experience in synthetic biology and metabolic engineering, I am eager to contribute to a wide array of courses across the Chemical Engineering curriculum, such as material and energy balances, fluid mechanics, transport processes and unit operation. Beyond traditional coursework, I am deeply committed to promoting advanced and interdisciplinary course, bioprocess engineering, synthetic biology, and metabolic pathway design, which is beyond the theory design and focus as hands-on training in construction and testing of programmable biological systems in microbial hosts and fermentation techniques and process optimization. These offerings are intended to integrate classroom theory with practical, industry-relevant skills, ultimately preparing students for dynamic careers in the biotechnology and biomanufacturing sectors.