Kuang To Investigate How Microbes May Rewrite Genetic Messages
Heidi Opdyke
- Associate Dean of Marketing and Communications, MCS
- Email opdyke@andrew.cmu.edu
- Phone 412-268-9982
Trillions of bacteria help digest food, shape the immune system and influence mood. Scientists have known for years that these microbes talk to host bodies in countless ways, and 麻豆村鈥檚 Zheng Kuang is exploring whether bacteria in the gut microbiota help decide which versions of a gene get turned on. The work could reveal new links between diet, microbes and disease and offer novel therapeutic strategies that target RNA isoforms instead of the genes themselves.
Every gene can be read in different ways, like a choose鈥憏our鈥憃wn鈥慳dventure book. This process 鈥� called alternative splicing 鈥� lets a single gene produce multiple versions of its message. These versions, called mRNA isoforms, can create proteins with very different jobs. Alternative splicing is a powerful tool cells use to fine-tune how the body works.
鈥淭his work will shift how the field conceptualizes how the microbiome regulates host biology, from changes in transcript abundance to selection among functional isoforms,鈥� said Kuang, Eberly Family Career Development Professor. His lab studies the ecosystem of intestinal bacteria and cells. 鈥淢ore broadly, it will inform future therapeutic or diagnostic strategies that target RNA isoform regulation rather than gene alone.鈥�
Kuang鈥檚 new project, 鈥淎 Splicing Language of Host Microbial Coevolution: Microbial Selection of Alternative Isoforms,鈥� could fundamentally change how scientists think about the microbiome鈥檚 influence on human biology.
Kuang proposes that the gut microbiota may influence which of these gene 鈥渟tories鈥� cells choose to tell. Depending on which version gets used, a body might adapt to the microrganism鈥檚 presence in healthy ways 鈥� or become more vulnerable to disease. To uncover this hidden world, the researchers will use cutting鈥慹dge sequencing tools and custom-built tests designed to track and measure these gene choices.
Kuang said he aims to look at how diet and microbes shape genetic choices, because different diets 鈥� like one of fast food or one with high fiber 鈥� can dramatically change the gut microbiome. By comparing how each microbiome influences alternative splicing in the gut, Kuang hopes to map out which splicing events are unique to certain diets and which are universal. This could reveal how flexible 鈥� or evolutionarily 鈥減lastic鈥� 鈥� gene regulation is in response to an environment.
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Kuang is also looking for the microbial molecules that flip the switch, so to speak.
Microbes produce a vast chemical world of metabolites 鈥� small molecules that can float into our bloodstream and influence many aspects of health. Kuang plans to test around 500 known microbial metabolites to see whether any of them shift the balance between different gene isoforms. If none do, the team will search for new ones.
For his efforts Kuang has been awarded a Hypothesis Fund, which supports foundational research too early for traditional grant programs. The fund empowers a diverse network of scientists Scouts to identify high-risk, high-reward ideas that challenge conventional thinking and address systemic risks to human and planetary health.
