New platform speeds bacterial gene mapping for better biotech design

Scientists at Oak Ridge National Laboratory have developed a platform that rapidly identifies genetic triggers in bacteria to create efficient biotechnology tools. By leveraging synthetic biology, artificial intelligence, and statistical mapping techniques, researchers were able to assess bacterial traits and pinpoint candidate genes responsible for desired characteristics.

The platform builds upon previous work by ORNL scientists who adapted protoplast fusion, a technique used to create genetically diverse bacterial offspring. This allowed for the discovery of specific genetic triggers that control complex traits in bacteria, enabling precise design for targeted applications such as breaking down plant lignin and absorbing critical minerals.

Unlike traditional methods that study the effect of whole gene gain or loss, this approach examines small nucleotide sequence differences, which greatly impact bacterial function. Researchers used quantitative trait locus (QTL) mapping to analyze the traits of many offspring from two distinct parents, identifying candidate genes in a single workflow.

However, limited genetic variation in bacteria posed a challenge, which was overcome by creating diverse recombinant populations through protoplast fusion. The team validated their findings using CRISPR gene-editing tools, confirming the effects of identified DNA variants. Automation and AI were employed to quickly phenotype the large population of bacteria, accelerating the process by tenfold.

This microbial QTL mapping platform, combining genome shuffling, automated phenotyping, statistical mapping, and CRISPR validation, is now available for licensing at ORNL and is being utilized for various research endeavors, including DOE efforts in bioenergy innovation, plant-associated microbes, and airborne microbes.