PNNL

A biological system is a group of entities (e.g. organs or cells) that work as a unit to achieve a common objective or goal. Functioning as a unified “system,” the work performed by biological systems impacts human life daily. For example, biological systems help cure diseases, produce our food, and provide substances, such as medicine, that we use every day. But exactly how biological systems perform their work (functions) remains largely a mystery.

Research shows that dissecting the genome allows us to predict only 10 percent of how biological systems function. Studying sequence after sequence, scientists attempt to tease out the changes in them to understand how or why they evolved. But the process doesn’t account for ever-changing environmental conditions like lifestyle factors, climate, and more, that surround proteins.

In fact, scientists could sequence genes for a lifetime and still fail to predict system function with sufficient reliability and accuracy to support manipulating biological systems used to improve human health or achieve other objectives.

With the Predictive Phenomics Initiative (PPI), Pacific Northwest National Laboratory (PNNL) is tackling the question of how protein expression alters biological system functionality differently. Through PPI, PNNL scientists are exploring the molecular basis of biological function to better understand and predict how genomes interact with the environment to produce phenotypes, and to develop capabilities to rationally design and control phenotypes. Put simply, they’re creating a rapid, verifiable, and repeatable process to harness the power of biological systems to develop revolutionary applications that will benefit humankind, and they’re starting with phenotypes.

A phenotype is a characteristic or trait of a biological system. For example, some biological systems naturally excrete more sugars as waste products and some digest atmospheric carbons as a food source. And others, like viral infection, have an uncanny ability to remain undetected for long time periods.

Scientists at PNNL are identifying measurable phenotypes—like the ones above—and using model systems such as soil microbes or human lung cells to observe if and how each molecular piece (lipids, metabolites, etc.) interacts with or changes protein structures.

The protein structure and its interaction with its chemical environment is critical because it drives enzyme activity, which promotes chemical reactions in a biological system and influences function. Yet changes in protein structures are also the most challenging to predict because of how outside variables critically impact them and their transient nature.

The long-term goal of PPI is to understand a function, model it, replicate it, and use it to improve or boost productivity within biological systems.