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LAB SCIENCE: Unraveling the mysteries of the tiniest living things

Patrick Chain, left, and Bin Hu

There are trillions of them – millions fitting through the eye of a needle – and they are everywhere. They live and thrive in vast communities in the environment, such as soil, rivers and oceans, and atmosphere, and in the human body. But they also exist in the oddest of places, such as extreme environments like volcanic hot springs and long-frozen ice in the Arctic.

Invisible to the human eye, they are communities of microorganisms, archaea (Greek for “ancient things”), fungi and viruses. Each community, or microbiome, can be thought of as an individual metropolis, each as different as New York City is from Albuquerque.

What’s fascinating about microbiomes is how they contribute to the “big” world. For example, various types of microbiomes thrive in the human body. Those in the human stomach help the gut absorb nutrients and minerals, as well as synthesize vitamins, enzymes (to help with digestion, among other things) and amino acids (the building blocks of proteins). This microbiome also helps train the body’s immune system battle tiny invaders, such as bacteria and viruses.

Scientists know little about the functions of many individual microbes. A deeper knowledge of these complex and ever-evolving communities – such as identifying the genes in each microbe – could unlock secrets improving human health, benefit habitats (such as using microbiomes to boost soil fertility by absorbing carbon from dead leaves), and help us develop new technologies for energy, environment, medicine and agriculture.

Currently, thousands upon thousands of data sets collected from different scientific environments throughout the world have already led to an understanding of the community membership of certain microbiomes. Now, researchers need the ability to compare and contrast many different microbiomes, such as microorganisms that form plaques inside the mouth versus others on the roof of the mouth – all different, but with some similarities. The problem is that scientists have created these data sets by collecting samples in many different ways, compiling data in different formats, and applying different analytical techniques to understand and interpret their results.

The key to understanding microbiomes is to unravel the genetic makeup of each microbe in a microbiome and establish a common data “language” that researchers can use to compare and contrast these complex communities, regardless of scientific discipline. To do this, the Department of Energy’s Office of Biological and Environmental Research has provided $10 million to establish a National Microbiome Data Collaborative. Spearheaded by Lawrence Berkeley National Laboratory, this collaborative consists of Los Alamos, Oak Ridge and Pacific Northwest national laboratories. By bringing together various scientific disciplines, the collaborative expects to unlock new possibilities derived from a better understanding of why microbiomes reside in specific environments and exactly how they work within their microbial communities.

The collaborative’s top goals are to provide easy and comprehensive access to all publicly available environmental microbiome data and to establish software tools allowing analyses that all scientists can use and replicate on their own. For their part, Los Alamos and Berkeley Lab will work out ways to take advantage of the supercomputers at Los Alamos and elsewhere within the DOE complex to create a common approach to collecting, classifying, interpreting and communicating various types of microbiome data, both old and new. This work is in its infancy, having just started in July 2019.

By standardizing the analytical process from start to finish, it will be possible to more adequately compare and contrast data from all different types of microbiomes, giving scientists of various disciplines an initial glimpse of the bigger picture when it comes to understanding the hows and whys of our microbial world. Tiny genetic differences that humans cannot see are easily picked up by computers using rapid algorithms that scan and track DNA sequences, which in turn can help unravel the genomes found in each microbe in a microbiome. Other software can help identify the genes or functional components within a microbe’s genome and determine if the sequences are similar or different from those of other microbes found in other environments.

In the 1953 movie “The War of the Worlds,” the closing line refers to a microbiome: “After all that men could do had failed, the Martians were destroyed and humanity was saved by the littlest things which God, in His wisdom, had put upon this Earth.” By addressing some of the fundamental roadblocks in microbiome data science, the National Microbiome Data Collaborative hopes to further the understanding of how the “littlest things” each contribute to the makeup of our world, and how we as humans can direct and ensure that these microbial communities benefit society.

A 2019 Laboratory Fellow, Patrick Chain works for the Biosecurity and Public Health group at Los Alamos National Laboratory. Bin Hu works for the Biosecurity and Public Health group at LANL. Hu has a Ph.D. in bioinformatics and is also a medical surgeon.

 

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