Bacteria and bacterial viruses (phages) are the most abundant members of the gut microbiota and are important drivers of human health. Despite the large amounts of sequencing and -omics data available on the human gut microbiome, it remains challenging to identify the molecular mechanism underlying associations between specific microbes and disease states. A major barrier in the field is our inability to readily infer function from sequencing data since microbes are extremely diverse with poorly annotated genomes. Furthermore, predicting gene functions often requires mechanistic knowledge of the protein family and phenotypic data, which can be difficult to obtain. To address these challenges, the Huang lab uses multidisciplinary approaches including functional genomics, genetics, biochemistry, and bioinformatics to study new pathways encoded in gut bacteria and phages.

We developed a high-throughput functional genomics platform, Barcoded Overexpression BActerial Shotgun Library Sequencing (Boba-seq), to interrogate gene functions at scale in a prominent group of gut anaerobes, Bacteroidales. These bacteria are highly abundant in the gut and are mostly associated with health due to their diverse repertoires of metabolic pathways and ability to access host-recalcitrant polysaccharides. DNA barcoding reduces the cost and increases the throughput of genome-wide genetic screens drastically. A major focus of the lab is to elucidate new roles and functions of genes important for nutrient acquisition and stress tolerance. We are also interested in identifying factors involved in bacteria-phage interactions. Phages are important members of the gut microbiota, but how they influence bacterial physiology and composition remains poorly understood.

The overarching goal in the lab is to advance our fundamental knowledge of molecular mechanisms underlying host-microbe-phage interactions. This will help us to better understand and predict the composition and functions of microbial communities under constant selections from microbial, host, and environmental factors.