Systems biology: new approaches to old environmental health problems

Abstract

The environment plays a pivotal role as a human health determinant and presence of hazardous pollutants in the environment is often implicated in human disease. That pollutants cause human diseases however is often controversial because data connecting exposure to environmental hazards and human diseases are not well defined, except for some cancers and syndromes such as asthma. Understanding the complex nature of human-environment interactions and the role they play in determining the state of human health is one of the more compelling problems in public health. We are becoming more aware that the reductionist approach promulgated by current methods has not, and will not yield answers to the broad questions of population health risk analysis. If substantive applications of environment-gene interactions are to be made, it is important to move to a systems level approach, to take advantage of epidemiology and molecular genomic advances. Systems biology is the integration of genomics, transcriptomics, proteomics, and metabolomics together with computer technology approaches to elucidate environmentally caused disease in humans. We discuss the applications of environmental systems biology as a route to solution of environmental health problems.

Figure 1

Central Dogma of Biology: Modern-omics technologies follow the pattern established by the central dogma of biology proposed more than 50 years ago by Watson and Crick [27], with the addition of active enzymes and metabolities, which taken together reflect human phenotypes. Here we include enzymes as part of the metabolome because metabolities are regulated by enzyme patterns.

Figure 2

Indirect Environment-Gene Interaction: Hormones and vitamins interact with the genome via ligand-activated transcription factors yielding a “normal” cellular response to maintain homeostasis. Environmental agents can mimic natural ligands or bind to other intracellular receptors that yield different information from homeostatic regulation. The result is an altered cellular response yielding an adverse health effect.

Figure 3

Simple Interaction Gene Regulatory Network: In the simple model, three interacting genes form a network in a cell. Here Gene A activates Gene B. Gene B activates Gene A and Gene C, and Gene C inactivates Gene A. Thus several levels of regulation are possible with the three interacting genes.