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Related Experiment Videos

New directions in incidence-dose modeling.

Melvin E Andersen1, James E Dennison, Russell S Thomas

  • 1CIIT Centers for Health Research, Six Davis Drive, PO Box 12137, Research Triangle Park, NC 27709-2137, USA. mandersen@ciit.org

Trends in Biotechnology
|March 1, 2005
PubMed
Summary

Cellular responses, like gene induction, often act as on-off switches. New mechanistic incidence-dose (ID) models incorporating this quantal nature improve biological risk assessments.

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Area of Science:

  • Systems Biology
  • Toxicology
  • Cellular Biology

Background:

  • Many cellular responses, including cell replication, differentiation, and apoptosis, are quantal, meaning they occur or do not occur.
  • Gene induction and coordinated cellular changes can also exhibit quantal behavior due to underlying molecular circuitry acting as on-off switches.

Purpose of the Study:

  • To develop mechanistic incidence-dose (ID) models that accurately represent the quantal nature of cellular switches.
  • To improve the biological basis of safety and risk assessments by incorporating these novel quantitative models.

Main Methods:

  • Utilizing interdisciplinary systems biology approaches.
  • Integrating detailed knowledge of cellular circuitry in signal transduction pathways.
  • Employing evolving biological modeling tools for cellular circuits and chemical perturbations.

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  • Leveraging high-throughput 'omic' screens to analyze cell signaling and biological responses.

    • Main Results:

    • Development of novel, quantitative mechanistic incidence-dose (ID) models for biological responses.
    • Improved understanding of how cellular switches contribute to dose thresholds and response incidence.

    Conclusions:

    • Mechanistic ID models must account for the quantal characteristics of cellular switches.
    • Interdisciplinary systems biology approaches are crucial for creating accurate biological response models.
    • These advancements will significantly enhance the biological foundation of safety and risk assessments.