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900 Walnut St.
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James S. Schwaber, PhD|
How Can Maintenance of Homeostasis Involve Adaptive Molecular Processes? The emergence of post-genomic data shows that very large networks of interacting genes, noncoding DNA and proteins determine biological functions and diseases. A systems biology approach is needed to decode these, leading to my current emphasis on developing these approaches for my long term interest in homeostasis and the visceral-emotional neuraxis. In this neuraxis parts of the brain involved with control of the viscera (e.g. cardiorespiratory function) interact with parts of the brain underlying stressful emotion (limbic areas). This interaction appears to play a role in a wide range of dysfunctions such as hypertension, sudden cardiac death, addiction/withdrawal and immune system functions (e.g. affecting susceptibility to cancer). More specifically, we at present are involved in systems biology projects to study (1) the brain's homeostatic adaptive processes related to hypertension, (2) the effects of withdrawal from chronic alcohol consumption in producing anxiety and cardiorespiratory dysfunctions, and (3) the interaction of the master circadian rhythm center of the brain (suprachiasmatic nucleus - SCN) with light, affecting homeostasis. In taking a systems biology approach to these, we (1) acquire global, system-wide datasets, (2) computationally analyze the data, (3) use the data to develop computational models (4) in which we can explore possible functional mechanisms and (5) develop experimentally testable hypotheses of systems function. To take the hypertension project as a specific example of our approach, the central nervous system has recently been shown to play a significant role in long term regulation of blood pressure, including the development and maintenance of hypertension. The mechanisms underlying these surprising but potentially very important cardiovascular homeodynamics are largely unknown. We hypothesize that the nucleus tractus solitarius (NTS), a major brain center mediating central and peripheral integration in cardiovascular control, adapts to transient, acute hypertensive events with a molecular remodeling that alters long-term regulatory function. In order to investigate this we have mounted a systems-level study of the cardiovascular NTS response to hypertension. This study involves examination of system-wide gene expression (transcriptional) regulation, short- and longer-term intracellular molecular signaling behavior, and the relation of these events to neuronal outputs, e.g. action potentials or "spiking" electrical behavior. Visit our website to learn more: www.dbi.tju.edu. |
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