Current Genomics, Vol. 5, No. 7, 2004
Contents
Hot
Topic: Systems Biology, from Archae to Man
Guest
Editor: John Aitchison
Systems Biology Experimental Design - Considerations for Building Predictive Gene Regulatory Network Models for Prokaryotic Systems Pp.527-544
Exploring Toll-Like Receptor Regulation of Innate
Immunity with the Tools of Systems Biology Pp.545-557
Kelly D. Smith and Vesteinn Thorsson
Transcriptional Complexity from Dynamic Interaction
Networks In Vivo Pp.559-566
Miroslav Dundr and Tom Misteli
Global Genomic Approaches to the Study of Human Gene
Function Pp.567-574
Peter D. Burbelo, Dana M. Pirone and Kathryn H. Ching
Mitochondrial Genomics and Proteomics Pp.575-588
Melissa S. Schonauer and Carol L. Dieckmann
Genome Variability in Gram-Positive Pathogenic Bacteria –
Impact on Virulence and Evolution Pp.589-600
Knut Ohlsen, Jorg Hacker and Wilma Ziebuhr
Current Perspectives in Genetics and Genomics of Alcohol
Dependence Pp.601-612
U.W. Preuss, G. Schultz, W.M. Wong, A.B. Watzke, S.
Barnow and J. Zimmermann
Abstracts
[Back to top]
Systems Biology Experimental Design - Considerations for Building Predictive
Gene Regulatory Network Models for Prokaryotic Systems
Marc T. Facciotti, Richard Bonneau, Leroy Hood and Nitin S. Baliga
The goal of systems biology is to describe and quantitatively model complete biological systems. It is a reasonable goal to begin by developing quantitative models that accurately recapitulate many aspects of gene regulatory networks for some simple organisms. We consider here the advantages of using prokaryotic organisms as model systems in the initial development of such quantitative models. In addition, we discuss some of the benefits of studying stress responses in these organisms and illustrate some of the biological and theoretical complexities facing the analyses of dynamic biological systems.
[Back to top]
Exploring Toll-Like Receptor Regulation of Innate Immunity with the Tools of
Systems Biology
Kelly D. Smith and Vesteinn Thorsson
[Back to top] Transcriptional
Complexity from Dynamic Interaction Networks In Vivo
Miroslav Dundr and Tom Misteli
The last decades have lead to the identification and characterization of most key steps in gene expression including chromatin remodeling, transcription, RNA processing, export and translation. Extensive biochemical, genetic and molecular approaches have not only revealed the key players involved in these processes, but have yielded detailed insights into the molecular behavior of many. Despite the wealth of molecular and structural information of distinct processes of gene expression and of single molecular components, fundamental aspects of the system behavior of the gene expression machinery have remained elusive. It is just now becoming clear that the single steps in the gene expression process are tightly interlinked and virtually nothing is known about how the various components of genome regulation and expression machineries are integrated into presumably complex networks of interactions and pathways. Even more elusive has been the elucidation of how gene expression processes occur in their natural setting of the cell nucleus in intact living cells. Recent advances in qualitative and quantitative imaging methods are beginning to provide tools to study the complexity of the gene expression process in living cells. We briefly review here some emerging in vivo imaging technologies and summarize the recent results and the conceptual impact these methods are making on understanding transcriptional complexity in vivo.
[Back
to top] Global Genomic Approaches to the Study of
Human Gene Function
Peter D. Burbelo, Dana M. Pirone and Kathryn H. Ching
The completion of the human genome project and the increasing availability of cDNAs to most genes made accessible the possibility of identifying the function of every gene. In contrast to most previous studies which typically examined one or a few human genes at a time for their biological effects, activity, or expression levels, new reagent sets and technological advances now allow large subsets or potentially even all human genes to be studied in a single experiment. Such high throughput approaches not only evaluate expression patterns of known genes, they may also be useful for assigning new activities to genes, placing them in signaling networks not previously known. Functional genomic studies that systematically manipulate either gene overexpression or gene knockdown via RNA interference are particularly useful for gaining global insights into gene function. Expansion of current genomic approaches to phenotypic and functional assays will likely provide new insights into the normal and pathological activities of many genes, undoubtedly accelerating the development of new therapeutic approaches for diagnosing, treating, and preventing disease.
[Back
to top] Mitochondrial Genomics and Proteomics
Melissa S. Schonauer and Carol L. Dieckmann
Factors involved in mitochondrial biogenesis and function have been studied classically via mutagenesis screens and subsequent genetic and biochemical analyses. The recent advent of high-throughput technologies has provided a wealth of information regarding mitochondrial function, morphology, gene regulation, protein complexes, and disease in a fraction of the time. This review will describe past and present genomic and proteomic methods used to study mitochondria both in yeast and mammalian cells, their advantages and limitations, and the current knowledge of the number of genes and proteins that are required for proper functioning of the organelle.
[Back
to top] Genome Variability in Gram-Positive Pathogenic Bacteria –
Impact on Virulence and Evolution
Knut Ohlsen, Jorg Hacker and Wilma Ziebuhr
The availability of complete genome sequences of more than 160 pathogenic and non-pathogenic bacteria is facilitating the understanding of evolution of bacterial virulence. Comparative genomics revealed that most pathogens have a relative by stable core genome, encoding factors essential for growth in a specific environment and a flexible gene pool, encoding virulence traits, resistance determinants and genes that confer gene-mobility such as transposons, integrases and insertion sequences. The flexible part of the genome often determines the virulence of a particular organism. This concept originally developed for Enterobacteriaceae is now being proven also for gram-positive pathogens such as staphylococci, streptococci and enterococci. For example, pathogenic staphylococci are now the most common cause of nosocomial infections. It is assumed that the enormous genome plasticity of staphylococci is the basis for the rapid adaptation of staphylococci in the highly selective environment of hospitals. The genome of pathogenic staphylococci consists of a complex mosaic of larger regions which have been acquired by horizontal gene transfer. Remarkably, mobile genetic elements such as resistance and pathogenicity islands, bacteriophages, IS-elements, plasmids, and transposons are widespread among clinical isolates. In this review, we summarise the recent results from comparative genomics studies of selected gram-positive bacterial pathogens and discuss the implications of these studies for the evolution of bacterial pathogenicity.
[Back
to top] Current Perspectives in Genetics and Genomics of Alcohol
Dependence
U.W. Preuss, G. Schultz, W.M. Wong, A.B. Watzke, S.
Barnow and J. Zimmermann
In the last two decades, a number of attempts have been made to unravel the complex genetic background of alcohol dependence. There is evidence from family, twin and adoption studies that the contribution of genetic factors accounts for 40-60% of alcohol dependence. In humans, the main approaches for investigating the complex genetics of alcoholism are linkage and association studies. Linkage studies reported alcoholism to be linked to only 5 chromosomal regions (on chromosomes 1, 7, and possibly 2, 4 and 5) and none of those loci reached a high statistical significance. Association studies are conducted by numerous research groups. They test a potential relationship between a certain genetic variant and alcoholism in a design similar to the classical case-control studies. Polymorphisms in the GABAergic, serotonergic, dopaminergic, and glutamatergic system have been related to alcohol- or alcoholism-associated phenotypes. Many studies failed to confirm initial positive results, raising doubts on the validity and replicability of this study approach. Recently more research has been conducted using genetic microarrays to investigate expression patterns of genes under the influence of chronic alcohol consumption. However, these approaches have several shortcomings, in particular their applicability in humans. In short, approaches in use for years by many research groups such as linkage and association studies showed either controversial or disappointing results. New approaches using endophenotypes and genetic microarrays may be helpful to shed light more light on the complex genetic background of alcoholism.