Dr. Kao's research focuses on genomics, systems biology and biotechnology. Her laboratory is interested in using genomic and systems biological tools to study microbial adaptation in various environments. Specifically, Kao is focusing on the use of adaptive laboratory evolution for two main applications: (1) to understand how opportunistic human fungal pathogens adapt to environmental stressors such as antifungal drugs in biofilms and (2) develop microbes such as yeast and bacteria for enhanced tolerance to toxic feedstock and products and to increase product formation. We are also exploring fermentation-based biopolymer formation for more sustainable materials development and have collaborations with Materials Engineering faculty to develop materials with anti-biofilm properties. 

EXAMPLE CURRENT PROJECTS:

Adaptive Evolution of Candida Biofilms

There is a critical need to identify important parameters involved in adaptation to environmental stresses in fungal biofilms, in order to develop effective therapeutic strategies against fungal infections. Treatment of fungal infections by Candida spp, including the emerging pathogen Candida glabrata (C. glabrata), remains a clinical challenge especially in immunocompromised individuals. C. glabrata is now the second most frequently isolated Candida spp in North America. In vivo, microbes mostly exist in biofilms, which serve as protective layers. Cells in biofilms exhibit increased resistance to environmental stresses. Since biofilms are an integral part of pathogenesis, the adaptation of fungal pathogens inside a biofilm is an important aspect that requires a deeper understanding. However, existing knowledge of fungal adaptation in biofilms is limited, partly due to the lack of established experimental methods for the long-term propagation of fungal biofilms. With a long-term goal of contributing to the development of therapeutic strategies for candidiasis, the overall objective of the project is to develop a fungal biofilm propagation method for use in experimental adaptive evolution in C. glabrata biofilms. This will be achieved by first developing a biofilm culture system suitable for long-term in vitro evolution will be developed and characterized. A key feature of the method being developed is the ability to grow multiple biofilms from the same seed biofilm, allowing multiple procedures for analysis and characterization of biofilms at each passage during in vitro evolution. We then implement the fungal biofilm propagation system for in vitro evolution of C. glabrata to environmental stressors. Key properties, such as amount of biofilm formation and changes in biofilm structure will be monitored. Molecular mechanisms associated with adaptation to environmental stressors in fungal biofilms will be elucidated based on genome-sequencing and phenotypic analyses. We will combine the biofilm propagation method with transposon sequencing to identify genes involved in biofilm formation in C. glabrata. The method being developed can be broadly applied to other microbial pathogens to better identify how pathogens adapt and evolve in a more host-relevant environment, and enables the identification of potential therapeutic strategies against difficult-to-treat biofilms.

Engineering yeast to produce value-added compounds

Plant-derived natural products are important sources of therapeutics or therapeutic precursors. Direct extraction of these compounds from plants face issues of low abundance, unpredictable crop yields, and some only available from ecologically sensitive regions. Chemical synthesis of these compounds often involve petrochemical-derived precursors. Thus, microbial-based production of these compounds has obvious advantages. Projects in the lab are focused on using laboratory adaptation and metabolic engineering of microbes to produce value-added compounds from plant-derived feedstocks. 

Biopolymers

We are developing fermentation-derived biopolymers for various applications.