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Open Access Research article

Large scale physiological readjustment during growth enables rapid, comprehensive and inexpensive systems analysis

Marc T Facciotti12*, Wyming L Pang1, Fang-yin Lo1, Kenia Whitehead1, Tie Koide1, Ken-ichi Masumura13, Min Pan1, Amardeep Kaur1, David J Larsen2, David J Reiss1, Linh Hoang4, Ewa Kalisiak4, Trent Northen4, Sunia A Trauger4, Gary Siuzdak4 and Nitin S Baliga1*

Author Affiliations

1 Institute for Systems Biology, 1441 North 34th Street, Seattle, WA 98103 USA

2 Department of Biomedical Engineering and UC Davis Genome Center, University of California, Davis, One Shields Ave, Davis, CA 95616 USA

3 Division of Genetics and Mutagenesis, National Institute of Health Sciences, Tokyo 158-8501, Japan

4 Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, Ca 92037 USA

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BMC Systems Biology 2010, 4:64  doi:10.1186/1752-0509-4-64

Published: 14 May 2010

Abstract

Background

Rapidly characterizing the operational interrelationships among all genes in a given organism is a critical bottleneck to significantly advancing our understanding of thousands of newly sequenced microbial and eukaryotic species. While evolving technologies for global profiling of transcripts, proteins, and metabolites are making it possible to comprehensively survey cellular physiology in newly sequenced organisms, these experimental techniques have not kept pace with sequencing efforts. Compounding these technological challenges is the fact that individual experiments typically only stimulate relatively small-scale cellular responses, thus requiring numerous expensive experiments to survey the operational relationships among nearly all genetic elements. Therefore, a relatively quick and inexpensive strategy for observing changes in large fractions of the genetic elements is highly desirable.

Results

We have discovered in the model organism Halobacterium salinarum NRC-1 that batch culturing in complex medium stimulates meaningful changes in the expression of approximately two thirds of all genes. While the majority of these changes occur during transition from rapid exponential growth to the stationary phase, several transient physiological states were detected beyond what has been previously observed. In sum, integrated analysis of transcript and metabolite changes has helped uncover growth phase-associated physiologies, operational interrelationships among two thirds of all genes, specialized functions for gene family members, waves of transcription factor activities, and growth phase associated cell morphology control.

Conclusions

Simple laboratory culturing in complex medium can be enormously informative regarding the activities of and interrelationships among a large fraction of all genes in an organism. This also yields important baseline physiological context for designing specific perturbation experiments at different phases of growth. The integration of such growth and perturbation studies with measurements of associated environmental factor changes is a practical and economical route for the elucidation of comprehensive systems-level models of biological systems.