Bridging the gap between high-throughput single-cell profiling and functional studies: understanding microbiota-animal interactions for pest management through microbiota
Functional analyses of unknown bacteria in the microbiota
To fully understand the function of bacterial microbiota, individual cells must be identified, targeted or isolated, and their functions should be studied at the molecular level, however, it is difficult with current techniques. Recently, we have developed a novel method (named BarBIQ) [Jin, et al., Nat. Commun., 2022], which firstly enabled to accurately and quantitatively characterize microbiota at single-cell level with single-base accuracy for genes (e.g., 16S rRNA genes), and independently of any databases, which means BarBIQ unbiasedly visualizes both the global microbiota and individual bacterial members. However, in order to understand the mechanism of the microbiota function and further manipulate them, this method should be combined with other functional analysis methods. Therefore, beyond BarBIQ, we will develop approaches that can do both high-throughput characterization and functional analysis. These approaches will not only identify unknown bacteria, but also determine the functions of the identified bacteria.
Mechanism study of microbiota-animal interactions
To fully understand the function of microbiota in its host (we focus on animals), studying the mechanisms of microbiota-animal interactions should be studied. Most current studies of microbiota-host interactions only addressed the association relationship between the microbiota and host, but were hard to answer the causal relationship or mechanism. On one hand, molecular studies (e.g., whole transcriptome sequencing) were only performed for the microbiota and host separately with rare and inaccurate integration. On the other hand, real-time observation of microbiota-host interactions by imaging is limited for molecular details. Recently, we developed an Automated Live-imaging and cell Picking System (ALPS), which successfully linked high quality imaging and whole transcriptome sequencing for the same cell [Jin et al., PNAS, 2023]. Next, we will develop new systems based on ALPS to study microbiota-host interactions using both imaging and sequencing. We hope these new systems with comprehensive analyses will help to understand the causal relationships between the microbiota and animal heath, behavior, etc., and the mechanisms of microbiota-host interactions.
Manipulation of bacteria in pests
Understanding the function of the bacterial microbiota and the causal relationships between the microbiota and animal heath or behavior is the first step, manipulating the microbiota based on the functional understanding to control the pest through their commensal microbiota is our ultimate goal. We will develop a complete pipeline to efficiently identify, functional understand, and manipulate any bacteria (whatever known or unknown) in pests.