Rice professor part of study that reveals competition for resources in gene expression

BY MIKE WILLIAMS
Rice News staff

Life is a competition even at the subcellular level, where genes do battle every second to gain the tiniest advantage.

MATTHEW BENNETT

That sort of competition extends to yeast, which are among the simplest eukaryotes for biologists to study; what makes bread rise also expands scientists’ knowledge of the inner life of cells. The mechanisms of gene transcripts in yeast are the subject of a new paper in the Proceedings of the National Academy of Sciences to which Matthew Bennett, an assistant professor of biochemistry and cell biology at Rice, was a major contributor.

Bennett, who holds a doctorate in theoretical physics but turned to biology as a postdoctoral researcher, helped set the ground rules and provided analytical tools for a study carried out in the lab of his former mentor, Jeff Hasty, a synthetic biologist at the University of California, San Diego (UCSD).

In the new paper, the researchers detail the workings of gene-expression transitions that, until the recent development of new tools for analysis, were too quick to see.

Bennett said the team took a close look at how a species of yeast, Saccharomyces cerevisiae, metabolizes two common sugars, galactose and glucose. “We were able to find new regulatory mechanisms for metabolizing these sugars that had never been seen. This was surprising because the system has been studied for a long time,” said Bennett of his previous work, published in Nature in 2008. In that study of the metabolic gene regulation and the regulated decay of messenger RNA transcripts – the “blueprint” for protein production – the team found that certain mRNA that normally decay in 15 to 20 minutes are destroyed within five minutes when the sugar in a yeast cell’s environment changes from galactose to its preferred meal of glucose. “It was unclear to us why that should be. Why would the cells want to degrade mRNA that is going to go away anyway?”

The new paper has answers, he said. “My colleague Bridget Baumgartner, a postdoctoral fellow in Hasty’s lab (and lead author), found that by doing so, the cells gain an advantage,” Bennett said. “When cells switch from a galactose to a glucose environment, they can switch to glucose metabolism quicker if they decay transcripts faster. The cells gain a little growth advantage, just a tiny bit – but evolution doesn’t need a lot.”

The study also found galactose-based mRNA competes for translational machinery with transcripts that regulate cell division – which gives the cell another reason to hasten its demise. “There’s a gene called CLN3, which is a regulator of when the cell decides it has enough energy to start making a daughter cell. Galactose transcripts compete with CLN3 transcripts, so if there are galactose transcripts around, CLN3 can’t start the cell cycle,” he said.

Bennett, who continues to study the dynamics of gene regulation in yeast and bacteria at Rice, said the next step would be “to quantify just how much of an advantage cells get” by rushing galactose transcripts out the door. He said the knowledge gained might become useful in synthetic biology. “As we learn more about how cells can manipulate and regulate gene expression in new ways, we might be able to engineer these forms of regulation into our synthetic networks.”

Co-authors of the paper are postdoctoral fellow Michael Ferry, Associate Professor Tracy Johnson and research scientist Lev Tsimring, all of UCSD.

The National Institutes of Health and General Medicine, the San Diego Center for Systems Biology and the Welch Foundation supported the research.