Controlled Measurement and Comparative Analysis of Cellular Components in E. coli Reveals Broad Regulatory Changes in Response to Glucose Starvation.
How do bacteria regulate their cellular physiology in response to starvation? Here, we present a detailed characterization of Escherichia coli growth and starvation over a time-course lasting two weeks. We have measured multiple cellular components, including RNA and proteins at deep genomic coverage, as well as lipid modifications and flux through central metabolism. Our study focuses on the physiological response of E. coli in stationary phase as a result of being starved for glucose, not on the genetic adaptation of E. coli to utilize alternative nutrients. In our analysis, we have taken advantage of the temporal correlations within and among RNA and protein abundances to identify systematic trends in gene regulation. Specifically, we have developed a general computational strategy for classifying expression-profile time courses into distinct categories in an unbiased manner. We have also developed, from dynamic models of gene expression, a framework to characterize protein degradation patterns based on the observed temporal relationships between mRNA and protein abundances. By comparing and contrasting our transcriptomic and proteomic data, we have identified several broad physiological trends in the E. coli starvation response. Strikingly, mRNAs are widely down-regulated in response to glucose starvation, presumably as a strategy for reducing new protein synthesis. By contrast, protein abundances display more varied responses. The abundances of many proteins involved in energy-intensive processes mirror the corresponding mRNA profiles while proteins involved in nutrient metabolism remain abundant even though their corresponding mRNAs are down-regulated.
Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas, United States of America; Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, Texas, United States of America.
John R
JR
Houser
Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas, United States of America; Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, Texas, United States of America.
Craig
C
Barnhart
Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas, United States of America; Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, Texas, United States of America.
Daniel R
DR
Boutz
Department of Organismic and Evolutionary Biology, Harvard University, Boston, Massachusetts, United States of America.
Sean M
SM
Carroll
Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas, United States of America; Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, Texas, United States of America.
Aurko
A
Dasgupta
Department of Organismic and Evolutionary Biology, Harvard University, Boston, Massachusetts, United States of America.
Joshua K
JK
Michener
Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas, United States of America; Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, Texas, United States of America.
Brittany D
BD
Needham
Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas, United States of America; Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, Texas, United States of America.
Ophelia
O
Papoulas
Center for Computational Biology and Bioinformatics, The University of Texas at Austin, Austin, Texas, United States of America.
Viswanadham
V
Sridhara
Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas, United States of America.
Dariya K
DK
Sydykova
Department of Organismic and Evolutionary Biology, Harvard University, Boston, Massachusetts, United States of America; Faculty of Arts and Sciences Center for Systems Biology, Harvard University, Boston, Massachusetts, United States of America; Department of Biological Sciences, University of Idaho, Moscow, Idaho, United States of America; Institute for Bioinformatics and Evolutionary Studies, University of Idaho, Moscow, Idaho, United States of America.
Christopher J
CJ
Marx
Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas, United States of America; Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, Texas, United States of America; Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America.
M Stephen
MS
Trent
Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas, United States of America; Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, Texas, United States of America; Center for Computational Biology and Bioinformatics, The University of Texas at Austin, Austin, Texas, United States of America; Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas, United States of America.
Jeffrey E
JE
Barrick
Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas, United States of America; Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, Texas, United States of America; Center for Computational Biology and Bioinformatics, The University of Texas at Austin, Austin, Texas, United States of America; Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas, United States of America.
Edward M
EM
Marcotte
Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas, United States of America; Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, Texas, United States of America; Center for Computational Biology and Bioinformatics, The University of Texas at Austin, Austin, Texas, United States of America; Department of Integrative Biology, The University of Texas at Austin, Austin, Texas, United States of America.
Claus O
CO
Wilke
D000465:Algorithms; D004926:Escherichia coli / Q000166:cytology / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D049490:Systems Biology / Q000379:methods*
D005947:Glucose