Systems biology approaches to uncover the role of gut microbes in PSC

Aided by the advent of the high-throughput data measurement era, systems biology approaches are ushering in a new period within Primary Sclerosing Cholangitis (PSC) research.

Systems biology provides a large-scale, global picture of disease, giving researchers a novel perspective that is different from more traditional, small-scale measurement approaches. A fairly new approach to PSC research, systems biology involves using computational modeling to examine all the biomolecular features that make up an organism and trying to understand how they work as a whol, while noting how differences affect the rest of the system. This approach allows researchers to further explore disease heterogeneity, complexity and emergent properties that demonstrate how the whole of a system is greater than the sum of its parts.

The effort to apply systems biology tools to PSC is led by Jaeyun Sung, Ph.D., who works in partnership with the laboratories of Konstantinos Lazaridis, M.D., and Nicholas LaRusso, M.D. Sung and his team provide computational analysis of high through-put data, turning the date into information that can be tested in a traditional wet-bench laboratory. Sung says that his group is largely focusing on the role of the gut microbiome in PSC.

"What we're looking into is not just a single bug, but the community of microbes in its entirety, which is the only way to understand collective function and behavior," he said.

This approach allows Dr. Sung and his team to cast a wide net, seeing all possibilities, and then narrowing them down to discover what could be differentiating a normal, healthy gut with one that has PSC. The team is also looking into the collective behavior of microbes as well as building classification models through the use of high-throughput data to discover new knowledge that could help to advance our understanding of PSC.

One apsect of the research that Dr. Sung is very interested in is uncovering how gut microbes may affect the liver, leading to PSC. "One of the main ways, that has yet to be really explored in the PSC literature, is what the gut microbes are making that may be influencing, mediating, or prolonging the disease." Dr. Sung said, "we have a long and challenging journey in front of us, but I'm optimistic."