Manuscript Topics

Chronic diseases such as cardiovascular disease and cancer are complex phenotypes. These diseases cannot be adequately understood by investigating individual genes, behaviors, environmental factors or signaling pathways without observing them in their functional context. Inherent in these complex phenotypes are emergent properties — new characteristics that evolve as the level of complexity increases from genes to proteins to tissues to organs. They are called emergent because they cannot be reduced to the properties of their constituent parts.

The body’s flexibility and ability to adapt to ever changing demands are what create the dynamic equilibrium observed in healthy organisms. Immune mechanisms that defend against invading bacteria, DNA repair mechanisms that repair mutations and prevent cancer, and feedback mechanisms that lower blood pressure when it becomes too high, are examples of how this dynamic equilibrium is maintained. If one system is overloaded, there are usually others in place to back it up. This state has previously been referred to as homeostasis but in fact involves a dynamic equilibrium where everything is constantly in flux but is maintained within certain boundaries defined as a ‘state space’. In health, all systems work together to keep the body healthy. But if load continues to increase and more and more systems are called upon to be continually active in the attempt to restore equilibrium, the dynamics can tip and become dysfunctional. At that point, a bifurcation, a new equilibrium is created around an unhealthy attractor that promotes disease. This can be illustrated in cancer where DNA repair and immune mechanisms cease to function in defense of tumor suppression and instead others kick-in to promote tumor growth and metastases.

This special issue on gene x environment interactions and systems biology in chronic disease solicits articles that address ways in which environmental factors interact with gene or protein expression to affect multiple systems in the body, or articles that address ways to intervene that incorporate a systems biology approach to treatment and prevention.

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