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CORVALLIS, Ore. – The Gordon and Betty Moore Foundation has selected an Oregon State University researcher to lead a study of chemical signaling and metabolite production among microbial communities whose origins trace back billions of years.

These “microbialites” encode much of the history of life on Earth – including the role ancient organisms played in the evolution of life and the shaping of environments.

Their metabolites could hold keys for advancing both human and environmental health.

OSU pharmaceutical sciences professor Kerry McPhail will work with collaborators at the University of Wisconsin, the University of California, San Diego, and Rhodes University in South Africa to study stromatolites, one of the two types of microbialites. Thrombolites are the other.

“‘Stromatolite’ is generally recognized to refer to the earliest known fossils of cyanobacterial-rich microbial mats, from the Archaean and Precambrian eras,” said McPhail, who received a $1,415,223 grant from the Moore Foundation. “These have been of intense geobiological and geochemical interest with regard to theories on the origin of life, and also biomineralization and lithification as related to global carbon cycling.”

Cyanobacteria, McPhail notes, are ubiquitous and well known for their ability to produce toxins, including those that kill cancer cells.

“If you want to find a natural medicine, look for a toxin in the environment,” she said.

Stromatolites and thrombolites are rocklike accumulations – multilayered sheets of microorganisms growing at interfaces between different types of material – that develop in limestone- or dolostone-forming environments. Stromatolites are laminar, whereas thrombolites are amorphous and clotted.

“The different underlying structures are associated with different microbial communities comprising a variety of bacteria and archaea,” McPhail said. “The discovery of actively accreting modern microbialites in 1956 at Shark Bay, Australia, allowed the investigation of these sedimentary deposits formed by the metabolic activity of microbial communities, which bind and trap sediments and induce the precipitation of calcium and magnesium carbonates.”

Metabolites are products of the life-sustaining chemical reactions within cells. Primary metabolites are necessary for cell growth; secondary metabolites, also known as natural products, are not, but they can perform important ecological functions.

Chemical signaling is how cells communicate with each other to coordinate their activities and maintain homeostasis.

The stromatolites McPhail’s team will study form a series of “barrage pools” – water can flow in but not out – along the southeastern coast of South Africa. The barrage pools comprise a vertical transect: a line running from the high intertidal area to low intertidal.

“The pools vary in salinity,” she said. “The upper pool is fed by freshwater with variable nitrogen and phosphate concentrations, and the lower pools are marine influenced. In preliminary studies of field-collected samples, phylogenetic analyses show significant differences in the types of bacteria present in stromatolites from upper and lower pools, and the presence of new and known cyanobacterial taxa related to known producers of biologically active secondary metabolites.”

Researchers have also identified known peptide secondary metabolites that inhibit protease enzymes – catalysts necessary for infection by viral or bacterial pathogens, including those that cause HIV/AIDS and cholera – and found unknown new metabolites not shared between samples from the different collection sites.

“In the lab, these bacterial communities rapidly precipitate calcium carbonate in both native water and artificial seawater,” McPhail said. “That enhances the opportunity to explore the dynamic process of microbialite formation and persistence.

“This project is about understanding what’s going on in these microbialites, and how they come to exist. We’ve always viewed fossil stromatolites as something very intriguing that speak to the origin of life, and to find these living ones has big implications. We can look at the chemical signaling in real time, over different time scales, including hours, days, weeks or seasons, and not just as a snapshot.”

That’s important because chemical signaling in a microbial community – like a conversation among a room full of people – involves a complex, developing mix of communiques. All of the people in the room are unlikely to simultaneously scream every word they know in a short-term burst, and bacteria don’t send out their signals in that manner either.

“If we want to know what the conversation is about, we have to sit and listen for a while, not just hear two words and jump to conclusions,” McPhail said. “With bacteria, it’s about volume control and expression of genes to make natural products in appropriate contexts. If we want to then interfere with bacterial virulence, for example, then we want to join or disrupt that conversation, and not in a way that’s driving drug resistance.”

The research team is aiming to add to the known vocabulary of chemical signaling. The scientists will do that by pushing the limits of instrumentation – including imaging by confocal microscopy, mass spectrometry and nuclear magnetic resonance spectroscopy – and combining that with metagenomics and secondary metabolite biosynthesis studies to detect new molecules and determine their structure and function.

“We first got samples from this stromatolite site in 2015,” McPhail said. “Chemical extracts from these samples were complex mixes of thousands of compounds; we couldn’t tell which metabolite was from which organism, and often each metabolite was in a very small amount. Biological activity screening will allow for the future design of specific assays to understand the ecological context of metabolite expression. That could lead to ways of manipulating microbial community structures, both for environmental and human health applications.”

The Gordon and Betty Moore Foundation selected McPhail for a Marine Microbiology Initiative grant after her research group presented a poster, “Stromatolite microbial communities as a source of new secondary metabolites,” in 2016 at the Joint Natural Products Conference in Copenhagen.

Gordon Moore, 88, is co-founder and chairman emeritus of Intel Corporation. The Moore Foundation was created “to tackle large, important issues at a scale where it can achieve significant and measureable impacts.”