A team led by scientists from the U.S. DOE Joint Genome Institute has analyzed the genes activated during algal lipid production, particularly the molecular machinery that orchestrates these gene activities inside the cell when it produces lipids.

“We know how to stress the algae,” said the study’s first author Chew Yee Ngan of the DOE JGI. “What we don’t know is how to keep the algae alive at the same time, until now.”

Researchers have walked a fine line between stressing the algae enough to produce lipids but not enough to kill them.

Until now, little was known about the protein factor that can regulate lipid production in Chlamydomonas reinhardtii, the reference genome for which was released in 2007.

The team cultured Chlamydomonas reinhardtii cells and starved them of nitrogen or sulfur, both of which are stress conditions to which the algae respond by producing lipids. Then the researchers analyzed the complex of DNA and proteins known as chromatin that define what genes are being activated, as well as the expression profiles or transcriptome, and compared these to nonstressed cells.

“We’re looking for changes in starved cells versus cells that are happily growing,” Ngan explained. Through careful analysis of genome-wide data sets, they narrowed down their search to identify two transcription factors that appeared to play a pivotal role in lipid accumulation, and then studied one of them, PSR1, in detail.

“In studying the chromatin modifications, we can read out changes in the proteins bound to DNA on a genome-wide scale and then specifically target those genes whose regulation profiles are changed under lipid-producing conditions,” Ngan said.

Study co-author Axel Visel, DOE JGI deputy for science programs, said, “The study also demonstrated how cells can be tricked into producing lots of lipid without dying of starvation by overexpression of PSR1, which is a strategy that could potentially be applied in other industrial algal species better suited for large-scale biofuel production.”

While the work is expected to help algal bioenergy researchers develop more targeted approaches for producing lipids for fuels, corresponding author Chia-Lin Wei, head of DOE JGI’s Sequencing Technologies Program, pointed out that this study also successfully demonstrated an effective strategy for the integration of epigenomic and gene expression data and methods—the mapping of molecular tags that sit on top of the actual DNA sequence and affect its function—in an organism relevant to DOE missions in energy and environment.

“Such functional interrogation of the genomes, as part of the JGI’s 10-Year Strategic Vision, is expected to be widely applicable to more plants and fungi whose gene regulatory pathways still prove elusive,” Wei said, adding that Ngan and others at the DOE JGI are continuing this work in many other energy-related species.

Their work was published online July 27 in the journal Nature Plants.