This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Weill Cornell Medicine investigators have developed a set of molecular tools to regulate the activity of specific genes in one of the most common classes of intestinal bacteria. The ability to genetically manipulate these microbes could lead to a better understanding of the role they play in human physiology and disease.
In healthy individuals, species of Clostridia comprise half of the bacteria found in the gut. Many produce metabolites that are likely beneficial for human health and immune regulation. However, some are associated with disease—from botulism and inflammatory intestinal conditions to metabolic disorders such as diabetes or even cancer.
Exactly how Clostridia contribute to disease onset or progression is not well understood. For example, do the bacteria produce a specific toxin or disease-affecting metabolite? Or could changes in their abundance alter other gut bacteria and influence health or disease?
"There is no way to answer this question without having a genetic toolset that will allow us to study the Clostridia obtained from clinical strains," said Dr. Chun-Jun "C.J." Guo, associate professor of immunology in medicine in the Division of Gastroenterology and Hepatology and a scientist at the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine. The toolsets that Guo and his team developed are described in a study published in Nature Biotechnology.
Ting-Ting Li and Xu Chen, both postdoctoral associates in the Guo lab at the time of the study, were the lead authors. To develop a tool for precisely controlling specific Clostridial genes, Guo and his team turned to the DNA sequences, also known as promoters, that normally regulate gene expression activity in these microbes. They tested 67 different regulatory sequences isolated from one strain of Clostridia and identified the one that directed the highest level of gene activity.
They then took this strong gene "promoter" and attached a "switch" that would allow them to turn the promoter on or off using a chemical inducer. The researchers—including collaborator Dr. Matthew Sorbara from the University of Guelph in Ontario—then inserted this controllable promoter into Clostridia and found that they could use their chemical inducer to regulate the levels of selected bacterial metabolic genes.
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