Systems Biology Opens the Blackest Boxes – Genetic Engineering & Biotechnology News

Immunitys Black Box

Few systems approach the complexity of our own immune system, which promotes a swift and powerful host defense by coordinating a dynamic, multiscale set of hierarchically organized molecular, cellular, and organismal components. I believe the immune system represents the original problem to be addressed by systems biology, declared Naeha Subramanian, Ph.D., assistant professor, Institute for Systems Biology. Immune cells respond to infection and environmental cues through a variety of intracellular and extracellular receptors.

Ligation of these receptors, Dr. Subramanian continued, leads to activation of many signaling cascades eliciting such processes as protein binding, phosphorylation, degradation, and nuclear localization that can subsequently alter gene expression. Dr. Subramanian then related this observation to her work, which focuses on deciphering the molecular mechanisms of innate immunity: The goal of my laboratory is to utilize a systems biology approach to examine these layers of information and derive hypotheses from emerging biological signatures.

According to Dr. Subramanian, small alterations in gene expression resulting from infection or homeostatic dysregulation may lead to significant pathological effects associated with autoimmunity and other immune diseases. By examining how expression changes more globally, we can detect such alterations, she explained. We now know, for example, that regulatory elements in the genome participate in normal immune responses.

However, when these networks are disrupted, as by underlying mutations or polymorphisms in proteins involved in these pathways, the resulting perturbations may initiate a snowball effect that drives disease. Thus, exposure to pathogens may predispose to expression changes associated with immune disorders.

According to Dr. Subramanian, taking a balanced, unbiased approach to data gathering and interpretation is of paramount importance. Decades of reductionist biological studies have catalogued enormous numbers of components ranging from genes and their products to intermediate metabolites, she noted. In the past, we thought of one protein in one pathway leading to one disease. However, that is not true. Rather, it is more like one protein into a black box of myriad interactions.

We need a systems biology approach to understand how these systems interact, she concluded. We need to know how these systems may sustain health or give rise to pathological phenotypes.

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Systems Biology Opens the Blackest Boxes - Genetic Engineering & Biotechnology News