- Email: [email protected]
Systems biology
Systems biology Editorial overview Alan Aderem Current Opinion in Biotechnology 2007, 18:331–332 Available online 2nd August 2007 0958-1669/$ – see front matter # 2007 Elsevier Ltd. All rights reserved. DOI 10.1016/j.copbio.2007.07.010
Alan Aderem Institute for Systems Biology, 1441 N. 34th Street, Seattle, WA 98103, USA e-mail: [email protected]
Alan Aderem is the Director and Cofounder of the Institute for Systems Biology. His research deals with complexity in the immune system with the ultimate aim of rational vaccine design.
Systems biology is now a burgeoning field. Technological and computational advances have enabled the acquisition and analysis of large datasets obtained by interrogating diverse biological systems at multiple levels. Global measurements of DNA have yielded sequence, genotype, and information about chromatin structure. RNA measurements have enabled genome-wide transcriptional profiling and information about alternative splicing and non-coding RNA. Proteomic approaches using mass spectrometry, and more recently protein arrays, have permitted the global identification and quantification of proteins in their biological context. Furthermore, these technologies have allowed the quantification of post-translational modifications and revealed dynamic protein–protein and protein–DNA interactions. Great strides have also been made in measuring metabolic fluxes, and emerging imaging technologies are providing tantalizing glimpses into biological function. However, despite these advances, the link between complex biological networks and phenotype remains an enormous challenge. The compendium of articles that follows addresses this question from various perspectives. Lucy Shapiro has focused on the temporal and spatial control of chromosome replication and segregation during the division of the bacterium, Caulobacter crescentus. She discusses a multidisciplinary approach that combines genomewide transcriptional profiling with powerful single molecule imaging to understand the molecular underpinnings by which subcellular organization orchestrates a crucial biological process. Tyers and Cook extend this theme to consider the control of cell size in yeast and metazoans. They describe how gene deletions, RNAi silencing, and imaging approaches provide global insights into the cross talk between the multiple biochemical pathways that govern this crucial attribute of biological systems. The much more daunting question of size control of organs and organisms is also discussed in the context of integrated system wide approaches. Davidson and Materna discuss the logic of transcriptional regulatory networks that coordinate developmental transitions in sea urchin embryos. They consider regulation in the context of a mathematical formalism that permits the prediction of unknown components of the network and the identification of inconsistencies within it. Kim and Zahn describe how they used global transcriptional profiling and high-throughput RNAi screens to identify genes that modulate aging in worms. These studies were extended to flies, mice, and humans in order to define tissue-specific and organ-specific mechanisms of senescence. Palsson and colleagues discuss advances in the inference of metabolic networks as well as efforts to map transcriptional regulatory networks in
www.sciencedirect.com
Current Opinion in Biotechnology 2007, 18:331–332
332 Systems Biology
microbial cells. They describe cases in which these networks are re-engineered for specific applications. Shmulevich and Price synthesize a variety of approaches to modeling biological networks. Two broad classes, biochemical reaction networks and statistical influence networks, are identified and examined in the context of their specific strengths and weaknesses. A major weakness in analyzing transcriptional profiling data is the implicit belief that regulated genes are functional in the particular biological context of the system
Current Opinion in Biotechnology 2007, 18:331–332
being studied. Barkai and colleagues leverage evolution to circumvent this problem. They perform cross-species comparisons of large-scale expression datasets to identify conserved features that are likely to represent functional elements within the system. Proteomics occupies a central position in the armamentarium of the systems biologist. However, increases in speed and data quality are hampered by significant technological limitations. Aebersold and colleagues discuss targeted mass spectrometry as a promising new approach to address these challenges.
www.sciencedirect.com
Alan Aderem Institute for Systems Biology, 1441 N. 34th Street, Seattle, WA 98103, USA e-mail: [email protected]
Alan Aderem is the Director and Cofounder of the Institute for Systems Biology. His research deals with complexity in the immune system with the ultimate aim of rational vaccine design.
Systems biology is now a burgeoning field. Technological and computational advances have enabled the acquisition and analysis of large datasets obtained by interrogating diverse biological systems at multiple levels. Global measurements of DNA have yielded sequence, genotype, and information about chromatin structure. RNA measurements have enabled genome-wide transcriptional profiling and information about alternative splicing and non-coding RNA. Proteomic approaches using mass spectrometry, and more recently protein arrays, have permitted the global identification and quantification of proteins in their biological context. Furthermore, these technologies have allowed the quantification of post-translational modifications and revealed dynamic protein–protein and protein–DNA interactions. Great strides have also been made in measuring metabolic fluxes, and emerging imaging technologies are providing tantalizing glimpses into biological function. However, despite these advances, the link between complex biological networks and phenotype remains an enormous challenge. The compendium of articles that follows addresses this question from various perspectives. Lucy Shapiro has focused on the temporal and spatial control of chromosome replication and segregation during the division of the bacterium, Caulobacter crescentus. She discusses a multidisciplinary approach that combines genomewide transcriptional profiling with powerful single molecule imaging to understand the molecular underpinnings by which subcellular organization orchestrates a crucial biological process. Tyers and Cook extend this theme to consider the control of cell size in yeast and metazoans. They describe how gene deletions, RNAi silencing, and imaging approaches provide global insights into the cross talk between the multiple biochemical pathways that govern this crucial attribute of biological systems. The much more daunting question of size control of organs and organisms is also discussed in the context of integrated system wide approaches. Davidson and Materna discuss the logic of transcriptional regulatory networks that coordinate developmental transitions in sea urchin embryos. They consider regulation in the context of a mathematical formalism that permits the prediction of unknown components of the network and the identification of inconsistencies within it. Kim and Zahn describe how they used global transcriptional profiling and high-throughput RNAi screens to identify genes that modulate aging in worms. These studies were extended to flies, mice, and humans in order to define tissue-specific and organ-specific mechanisms of senescence. Palsson and colleagues discuss advances in the inference of metabolic networks as well as efforts to map transcriptional regulatory networks in
www.sciencedirect.com
Current Opinion in Biotechnology 2007, 18:331–332
332 Systems Biology
microbial cells. They describe cases in which these networks are re-engineered for specific applications. Shmulevich and Price synthesize a variety of approaches to modeling biological networks. Two broad classes, biochemical reaction networks and statistical influence networks, are identified and examined in the context of their specific strengths and weaknesses. A major weakness in analyzing transcriptional profiling data is the implicit belief that regulated genes are functional in the particular biological context of the system
Current Opinion in Biotechnology 2007, 18:331–332
being studied. Barkai and colleagues leverage evolution to circumvent this problem. They perform cross-species comparisons of large-scale expression datasets to identify conserved features that are likely to represent functional elements within the system. Proteomics occupies a central position in the armamentarium of the systems biologist. However, increases in speed and data quality are hampered by significant technological limitations. Aebersold and colleagues discuss targeted mass spectrometry as a promising new approach to address these challenges.
www.sciencedirect.com