Systems Biology is about combining theory, technology, and targeted experiments in a way that dri... more Systems Biology is about combining theory, technology, and targeted experiments in a way that drives not only data accumulation but knowledge as well. The challenge in Systems Biomedicine is to furthermore translate mechanistic insights in biological systems to clinical application, with the central aim of improving patients' quality of life. The challenge is to find theoretically well-chosen models for the contextually correct and intelligible representation of multi-scale biological systems. In this review, we discuss the current state of Systems Biology, highlight the emergence of Systems Biomedicine, and highlight some of the topics and views that we think are important for the efficient application of Systems Theory in Biomedicine.
Summary Objective: To discuss interdisciplinary research and education in the context of informat... more Summary Objective: To discuss interdisciplinary research and education in the context of informatics and medicine by commenting on the paper of Kuhn et al.“Informatics and Medicine: From Molecules to Populations”. Method: Inviting an international group of experts in biomedical and health informatics and related disciplines to comment on this paper. Results and Conclusions: The commentaries include a wide range of reasoned arguments and original position statements which, while strongly endorsing the educational needs ...
The molecular basis of the mouse mutation (), which is associated with spina bifida and exencepha... more The molecular basis of the mouse mutation (), which is associated with spina bifida and exencephaly, was analyzed at three of its alleles, , and . We mapped the paired box gene within the to interval, near or at the locus on ...
Previous studies have identified a single amino-acid substitution in the transcriptional regulato... more Previous studies have identified a single amino-acid substitution in the transcriptional regulator Pax-1 as the cause of the mouse skeletal mutant undulated (un). To evaluate the role of Pax-1 in the formation of the axial skeleton we have studied Pax-1 protein expression in early sclerotome cells and during subsequent embryonic development, and we have characterized the phenotype of three different Pax-1 mouse mutants, un, undulated-extensive (unex) and Undulated short-tail (Uns). In the Uns mutation the whole Pax-1 locus is deleted, resulting in the complete absence of Pax-1 protein in these mice. The other two genotypes are interpreted as hypomorphs. We conclude that Pax-1 is necessary for normal vertebral column formation along the entire axis, although the severity of the phenotype is strongest in the lumbar region and the tail. Pax-1-deficient mice lack vertebral bodies and intervertebral discs. The proximal part of the ribs and the rib homologues are also missing or severely ...
Introduction After more than 50 years of classical genetics, developmental genetics of the mouse ... more Introduction After more than 50 years of classical genetics, developmental genetics of the mouse has entered a new phase. The recent advances in molecular biology enable the old questions in developmental biology to be addressed with new methods. Traditionally, mouse genetics has centered around the study of a large number of mutants that either occurred spontaneously or were induced by experimental mutagenesis. The biological questions that were asked were mainly dictated by the nature of the mutants available. Although phenotypic consequences of mutated genes could be analyzed, the nature of the genes themselves remained unknown. Reverse genetics has changed this situation dramatically. We now have many genes at hand whose functions remain to be discovered. A major focus is on the identification and analysis of developmental control genes in vertebrates. Genetic and molecular studies of developmental processes in Drosophila melanogaster have revealed that embryogenesis is under the control of a cascade of genes directing developmental decisions and orchestrating complex processes, such as cell commitment and differentiation. Mutations affecting the formation of metameric units (segmentation genes) or the identity of segments (homeotic genes) facilitated the identification of a gene regulatory network in which a limited number of key regulatory genes control developmental pathways in the fruit fly (Gehring and Hiromi, Annu. Rev. Genet., 20, 147-173, 1986; Akam, Development (Cambridge), 101, 1-22, 1987; Ingham, Nature (London), 335, 25-34, 1988). Is vertebrate embryogenesis, likewise, under the control of similar genes? The cloning of Drosophila homeotic and segmentation genes has identified at least three types of conserved sequence motifs among these developmental control genes. Low stringency cross-hybridization strategies then led to the identification of a large number of vertebrate genes that have also conserved these sequences. The question therefore arises whether the homeobox, paired-box, and zinc-finger containing genes of the mouse play a similar role in development as their counterparts in Drosophila. To answer this question, three approaches are currently being pursued in the functional analysis of candidate mouse development control genes.
Systems Biology is about combining theory, technology, and targeted experiments in a way that dri... more Systems Biology is about combining theory, technology, and targeted experiments in a way that drives not only data accumulation but knowledge as well. The challenge in Systems Biomedicine is to furthermore translate mechanistic insights in biological systems to clinical application, with the central aim of improving patients' quality of life. The challenge is to find theoretically well-chosen models for the contextually correct and intelligible representation of multi-scale biological systems. In this review, we discuss the current state of Systems Biology, highlight the emergence of Systems Biomedicine, and highlight some of the topics and views that we think are important for the efficient application of Systems Theory in Biomedicine.
Summary Objective: To discuss interdisciplinary research and education in the context of informat... more Summary Objective: To discuss interdisciplinary research and education in the context of informatics and medicine by commenting on the paper of Kuhn et al.“Informatics and Medicine: From Molecules to Populations”. Method: Inviting an international group of experts in biomedical and health informatics and related disciplines to comment on this paper. Results and Conclusions: The commentaries include a wide range of reasoned arguments and original position statements which, while strongly endorsing the educational needs ...
The molecular basis of the mouse mutation (), which is associated with spina bifida and exencepha... more The molecular basis of the mouse mutation (), which is associated with spina bifida and exencephaly, was analyzed at three of its alleles, , and . We mapped the paired box gene within the to interval, near or at the locus on ...
Previous studies have identified a single amino-acid substitution in the transcriptional regulato... more Previous studies have identified a single amino-acid substitution in the transcriptional regulator Pax-1 as the cause of the mouse skeletal mutant undulated (un). To evaluate the role of Pax-1 in the formation of the axial skeleton we have studied Pax-1 protein expression in early sclerotome cells and during subsequent embryonic development, and we have characterized the phenotype of three different Pax-1 mouse mutants, un, undulated-extensive (unex) and Undulated short-tail (Uns). In the Uns mutation the whole Pax-1 locus is deleted, resulting in the complete absence of Pax-1 protein in these mice. The other two genotypes are interpreted as hypomorphs. We conclude that Pax-1 is necessary for normal vertebral column formation along the entire axis, although the severity of the phenotype is strongest in the lumbar region and the tail. Pax-1-deficient mice lack vertebral bodies and intervertebral discs. The proximal part of the ribs and the rib homologues are also missing or severely ...
Introduction After more than 50 years of classical genetics, developmental genetics of the mouse ... more Introduction After more than 50 years of classical genetics, developmental genetics of the mouse has entered a new phase. The recent advances in molecular biology enable the old questions in developmental biology to be addressed with new methods. Traditionally, mouse genetics has centered around the study of a large number of mutants that either occurred spontaneously or were induced by experimental mutagenesis. The biological questions that were asked were mainly dictated by the nature of the mutants available. Although phenotypic consequences of mutated genes could be analyzed, the nature of the genes themselves remained unknown. Reverse genetics has changed this situation dramatically. We now have many genes at hand whose functions remain to be discovered. A major focus is on the identification and analysis of developmental control genes in vertebrates. Genetic and molecular studies of developmental processes in Drosophila melanogaster have revealed that embryogenesis is under the control of a cascade of genes directing developmental decisions and orchestrating complex processes, such as cell commitment and differentiation. Mutations affecting the formation of metameric units (segmentation genes) or the identity of segments (homeotic genes) facilitated the identification of a gene regulatory network in which a limited number of key regulatory genes control developmental pathways in the fruit fly (Gehring and Hiromi, Annu. Rev. Genet., 20, 147-173, 1986; Akam, Development (Cambridge), 101, 1-22, 1987; Ingham, Nature (London), 335, 25-34, 1988). Is vertebrate embryogenesis, likewise, under the control of similar genes? The cloning of Drosophila homeotic and segmentation genes has identified at least three types of conserved sequence motifs among these developmental control genes. Low stringency cross-hybridization strategies then led to the identification of a large number of vertebrate genes that have also conserved these sequences. The question therefore arises whether the homeobox, paired-box, and zinc-finger containing genes of the mouse play a similar role in development as their counterparts in Drosophila. To answer this question, three approaches are currently being pursued in the functional analysis of candidate mouse development control genes.
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