MBI Begins 200607 Program in Systems Physiology

October 21, 2006

Systems physiology is the theme for 200607 at the Mathematical Biosciences Institute, Ohio State University. Researchers in systems physiology seek to understand how various human organs and tissues are organized and regulated both during normal function and in the development of pathologies.

Participants in this year's program, says MBI director Avner Friedman, "will examine features of several human organ and tissue systems, including the cardiac system, the respiratory system, the microcirculatory system, the renal system, the visual processing system, the endocrine system, and the auditory system." Although these systems are at first glance quite different, the underlying theme is how cellular-level behavior participates in the function of the whole and how feedback from that function contributes to the regulation of behavior at the cellular level. "Understanding of these processes may lead to new insights into the causes of diseases and how they can be treated," Friedman adds.

Jim Keener, one of the organizers of the year's program, emphasizes two important organizing principles: "First, an integrated understanding of systems requires mathematics and the development of theory, supplemented by simulations; secondly, theory cannot be relevant if it is not driven and inspired by experimental data."

"The goal of the workshops throughout the year" Keener says, "is to bring together theoreticians and experimentalists in order to catalyze a deeper understanding of these complex systems."

Keener and Raimond Winslow are the organizers of the first workshop, which will concentrate on atrial and ventricular electrophysiology, from models of the biophysics of single ion channels to predicting the electrocardiogram recorded at the body surface. Winslow identifies the workshop's overarching theme: "how mathematical models can elucidate mechanisms, improve diagnoses and identify therapeutic targets for cardiac arrhythmias."

A second workshop will address the mechanical function of the heart, from models of the biophysics and biochemistry of molecular motors to predicting the three-dimensional mechanical performance of the whole heart. "The theme threading through this workshop," says Andrew McCulloch, "will be how mathematical models can improve the diagnosis and treatment of cardiac mechanical dysfunction during disease, especially congestive heart failure, and elucidate the mechanisms by which mechanical factors can regulate cardiac remodeling in vivo."

Also scheduled for the autumn of 2006 is a workshop on the lungs and respiratory system. According to Ken Luchen, who with Jason Bates and Bela Suki is a co-organizer of the workshop, computational modeling promises a new era in the fundamental understanding of how lung morphometry and biomechanical/biomaterial properties impact lung function. As imaging modalities improve, Luchen says, it is "increasingly possible to establish precise physical locations and degrees of structural or functional defects in the lung during disease." Such data beg the question of how explicit defects of biological components, processes, and structure at specific anatomic locations alter function, Luchen explains. Computational power now available makes it possible to develop models that are close anatomic replicas of a real lung, while incorporating the fundamental biophysical properties and relations for each component of each airway in exquisite detail.

For the winter quarter, Tim Secomb and Daniel Beard are the organizers of a workshop on blood flow and its control: microcirculation, blood pressure, and smooth muscles. "Since the vessels to be considered are very thin (less than 100 mm)," Secomb explains, "short-term local control of blood flow is provided by the ability of vessels to change their diameters by contraction and relaxation of vascular smooth muscle." Understanding this system has important implications both for normal physiological processes and for many diseases, including heart disease, hypertension, and cancer. "Mathematical and computational ap-proaches based on continuum and multiphase models can make important contributions in all these areas," Secomb says.

Scheduled for later in the year are workshops on renal physiology, information processing in the visual system, and the auditory system. One workshop in particular---Insulin Secretion, Insulin Action, and Type 2 Diabetes---is notable for its timeliness. "The current rise in the rates of type 2 diabetes mellitus (T2DM) combined with the rapid expansion of knowledge of the basic biology present great opportunities for mathematical modeling," says Artie Sherman, one of the organizers. It is well appreciated within the diabetes research community that T2DM is a multifactorial disease that involves interactions over disparate spatial scales (from genes to cells to organs to the whole body) and time scales (from milliseconds to decades). In addition, genetic, metabolic, and ionic events all have to be integrated to achieve a workable understanding of normal and pathological regulation.

Sherman believes that the workshop will be valuable both for exposing the current and future generations of modelers to new problem areas and for showcasing areas in which progress has already been made to experimentalists.
"The last decade has uncovered the genetic basis for many diseases," Keener says in summary. "A remaining and larger challenge is to provide an understanding of how the interactions of these biological entities across spatial and temporal scales lead to observable behavior and function."

Mathematicians, statisticians, and computational scientists, along with biologists, are encouraged to apply to participate in the annual program and other workshops at MBI (http://www.mbi.osu.edu/applyworkshop.html). MBI also welcomes suggestions for new programs from the research community.---Avner Friedman, Director, Mathematical Biosciences Institute.

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