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New imaging mass spectrometry methods for natural products research
Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) is one of imaging mass technology used for providing high spatial resolution of chemicals. Application of MALDI IMS on microbial samples opens a new window to explore the metabolic communication between microorganisms, and subsequently to discover new therapeutics (for human disease) or biological control agents (for agricultural disease). However, MALDI IMS has many limitations, for example, it is difficult to analyze small molecular natural products (< m/z 600) because of the interference of matrix signals. The sensitivity and reproducibility are another bottlenecks of MALDI IMS. Surface-assisted laser desorption/ionization (SALDI) has been developed in the last several years to be one of the potential solutions for detecting small molecules, however, it has been nearly utilized for IMS analysis. In this project, we intend to develop different SALDI substrates, such as SiO2 and TiO2, for small molecular IMS on various types of biological samples. We primarily apply the newly developed technique to investigate the metabolic exchange of microbial interaction. |
New biocontrol agents for agricultural diseases control
In this project, we intend to develop alternative biocontrol agents for controlling agricultural pests and pathogenic microbes. In the pest control project, we focus on the pathogenesis of entomopathogenic fungus, Beauveria bassiana. Entomopathogenic fungi are widely distributed with both restricted (obligate pathogens) and wide host ranges (facultative pathogens) which have different biocontrol potentials against insects and plant pathogenic microbes. B. bassiana was among the first organisms to be used for the biocontrol of pest insects. However, the functional roles of natural products participating in the interactions between B. bassiana and host (insects and plants) have rarely been clarified. Currently, we are working with Dr. Alongkorn Amnuaykanjanasin (National Center for Genetic Engineering and Biotechnology, Thailand) on exploring the functions of natural products in the pathogenesis of B. bassiana.
In this project, we intend to develop alternative biocontrol agents for controlling agricultural pests and pathogenic microbes. In the pest control project, we focus on the pathogenesis of entomopathogenic fungus, Beauveria bassiana. Entomopathogenic fungi are widely distributed with both restricted (obligate pathogens) and wide host ranges (facultative pathogens) which have different biocontrol potentials against insects and plant pathogenic microbes. B. bassiana was among the first organisms to be used for the biocontrol of pest insects. However, the functional roles of natural products participating in the interactions between B. bassiana and host (insects and plants) have rarely been clarified. Currently, we are working with Dr. Alongkorn Amnuaykanjanasin (National Center for Genetic Engineering and Biotechnology, Thailand) on exploring the functions of natural products in the pathogenesis of B. bassiana.
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In the microbial pathogens project, we intend to explore the potentials of microbiome as biocontrol agents. Microbes exist in virtually every niche in the world, where they colonize the internal tissues of the host plant (endophytes) or insect (gut microbiome) can form a range of various relationships including symbiotic, mutualistic, commensalistic and trophobiotic. Currently, we are working on developing biocontrol agents of banana Fusarium wilt. We first analyze the microbiome from different banana cultivars to find out the “microbial hub species” for specific cultivars and employ in situ metabolomics and RNA-seq to visualize the metabolic exchange of interactions between microbial hub species, Fusarium and banana. After obtaining data and formulating hypotheses based on aforementioned data, we will isolate or synthesize the key metabolites and evaluate their true biological functions in the interaction, which may benefit the development of methods to control Fusarium wilt of banana.
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Engineering biosynthetic enzymes for natural products synthesis
Conjugated polyynes are unstable secondary metabolites with various biological functions mainly identified from plants, marine organisms, and fungal sources. However, only a few conjugated polyynes have been identified from bacteria. We have identified that the conjugated polyynes, isolated from Massilia sp. YMA4, inhibit the growth of Candida albicans and some drug-resistant Candida clinical isolates via blocking the biosynthesis of ergosterol, the main component of the fungal cell membrane. Meanwhile, we have established a synthetic biology platform to generate various conjugated polyyne structures for evaluating their biological functions. We anticipate that this project's outcomes would demonstrate the power of the integrated omics approach and establish a model for therapeutic leads discovery from natural products. The participants of this multidisciplinary project will have comprehensive training and gain knowledge about natural products chemistry, bioinformatics, biochemistry, molecular biology, and synthetic biology.
Conjugated polyynes are unstable secondary metabolites with various biological functions mainly identified from plants, marine organisms, and fungal sources. However, only a few conjugated polyynes have been identified from bacteria. We have identified that the conjugated polyynes, isolated from Massilia sp. YMA4, inhibit the growth of Candida albicans and some drug-resistant Candida clinical isolates via blocking the biosynthesis of ergosterol, the main component of the fungal cell membrane. Meanwhile, we have established a synthetic biology platform to generate various conjugated polyyne structures for evaluating their biological functions. We anticipate that this project's outcomes would demonstrate the power of the integrated omics approach and establish a model for therapeutic leads discovery from natural products. The participants of this multidisciplinary project will have comprehensive training and gain knowledge about natural products chemistry, bioinformatics, biochemistry, molecular biology, and synthetic biology.
