PNNL Life Scientists Are Pioneering Predictive Phenomics

It is well known that genes are the instruction book for life. They determine whether we are born with blue eyes, brown hair or a predisposition to certain diseases. 

However, our genetic makeup is only part of the equation. The environment is the other. For example, brown hair could get bleached by the summer sun, or a healthy lifestyle may deter an illness from manifesting. 

Researchers at the Department of Energy’s Pacific Northwest National Laboratory are studying the rich and dynamic interactions that lead to the collection of an organism’s observable traits, which is known as its phenome. 

There are many examples of the phenome phenomenon in nature that illustrate how an organism’s genes and its environment result in interesting traits. 

For instance, genetics alone do not account for a flamingo’s pink feathers. The color is the result of a constant diet of shrimp. Similarly, the sex of sea turtle hatchlings is not genetically pre-programmed within the eggs but determined by the temperature of the surrounding sand during incubation.

While flamingos and sea turtles help explain phenomics, they are not the focus of research at PNNL.

Instead, life scientists are studying the relationship between genetics and environmental influences in microbes—the dominant form of life on Earth based on sheer numbers. In particular, they seek to predict how microbes might respond to different environmental conditions, stressors or treatments.

With that knowledge, they can engineer the environment to achieve desired outcomes. PNNL innovators are bringing multidisciplinary strengths in chemistry, biology, engineering and artificial intelligence to bear on this nascent field of “predictive phenomics.” 

They aim to position the United States as a leader in the emerging $4 trillion bioeconomy, with applications ranging from precision medicine and resilient agriculture to biosensors for national security and biobased material production. 

By leveraging PNNL’s expertise in molecular measurement and data science, scientists are developing sophisticated models to understand how the molecular function of viruses, bacteria and other microbes respond to changes in their environment. 

In one effort, scientists developed a screening process to explore whether they could create a new microbial community that acts as a catalyst for producing ammonia, which provides the fixed nitrogen needed to produce fertilizers, biofuels and other commodities. Their approach may offer a more efficient alternative to today’s methods for ammonia production.

The researchers used their screening process to investigate the result of pairing two specific microorganisms—adjusting their “environment” by creating a microbial community where new traits emerge based on their interactions. They combined a yeast that degrades lipids and proteins for producing biofuels with a bacterium that captures nitrogen from the air and secretes ammonium. By bringing them together, they enabled a biologically based method for nitrogen fixation. 

In another effort, scientists studied the role that “good cholesterol” plays in removing the “bad cholesterol” that builds up in our arteries, threatening our heart health. Researchers predicted that a particular protein found in most good cholesterol, known as high-density lipoproteins or HDLs, would boost the removal of bad cholesterol from arteries. 

Through testing, they determined that adding the protein produced the desired effect—demonstrating how an environmental trigger (an HDL protein) could change observable traits (improved cholesterol regulation).

In yet another example, researchers are exploring how to increase soil’s capacity for long-term carbon storage. Unlike genetic engineering, which would involve tinkering with the microbe’s DNA, scientists are influencing outcomes by tweaking environmental factors, such as which beneficial microbes are present. 

With plants constantly capturing carbon dioxide from the atmosphere, this work focuses on pushing that carbon down into the soil where it could be converted to new stable and storable forms. 

As pioneers in predictive phenomics, scientists at PNNL seek to harness the power of this new field. Their work is shaping a revolutionary approach to biological research that opens the door to promising solutions for a brighter future. 

Steven Ashby, director of Pacific Northwest National Laboratory, writes this column monthly. To read previous Director's Columns, please visit our Director's Column Archive.