A new study by researchers at the University of 蓝莓视频 has uncovered a crucial mechanism in the evolution of regulatory systems in E. coli that could have far-reaching applications in cancer therapy and biomanufacturing for products such as insulin or mRNA vaccines.
This discovery stems from a long-term experiment initiated by Richard Lenski, in which E. coli bacteria have been grown in a glucose-only environment for the equivalent of a few million years in human terms. The Lenski experiment was designed to record the adaptations that occur in bacteria in a controlled laboratory environment. However, deciphering the observed changes has been challenging due to the sheer volume of data.
The critical insight arose when the research team examined a regulatory mechanism near the tail end of a protein called PykF
鈥淎 helpful analogy to understand this mechanism is the speedometer in a car. When you're driving through a town, where there are dangers to avoid, you need to know how fast you're going, so the speedometer is important. But, if you're on an open stretch of road with no risks, you can throw the speedometer out the window and put the pedal to the metal,鈥 said Dr. Christian Euler from the Department of Chemical Engineering. 鈥 The research opens up the potential to one day put a new stoplight on the road to limit growth rate.鈥
PykF acts like a speedometer for carbon metabolism. Its deletion effectively removes this 鈥榮peedometer鈥. As a result, the bacteria can grow faster and more efficiently
Although E. coli and cancer cells are different, they share a similar mechanism. This research found that this mechanism can be lost under controlled conditions, allowing cells to grow faster.
Cancer cells in solid tumours create a controlled microenvironment that may bypass this regulatory process, driving rapid growth. This unchecked growth is how cancer becomes deadly.
Understanding these changes could help researchers better understand cancer evolutionary dynamics to inform therapies and design better microbial strains for biomanufacturing.
鈥淭he cells could be genotyped to investigate the mutations and their role in the type of cancer the patient has, and it could inform treatment protocols,鈥澨齭aid Dr. Matthew Scott a professor in the Department of Applied Mathematics.听听 鈥淢ore directly, we could introduce a chemical that "resets the speedometer," neutralizing the advantage gained from this adaptation.鈥
The potential applications of this discovery are significant. In cancer cells, the loss of similar regulatory mechanisms might offer a growth advantage to healthy cells.
鈥淭his finding is not just a fundamental advancement in understanding bacterial evolution,鈥 said Euler. 听鈥淚t could redefine practices in both healthcare and industrial biotechnology, potentially improving cancer treatments.鈥
In the Lenski experiment, cells were grown on glucose. The research team is investigating whether the same mechanisms are at play on other carbon sources, like glycerol, and acetate. This would help to establish it as a universal aspect of metabolic regulation.
The appears in Nature Communications journal.