ARGENTINE ANTS: A SYSTEM A STUDY GENES INVOLVED IN HUMAN BEHAVIORAL DISEASE
Christopher David Smith
San Francisco State University, 1600 Holloway Ave, Adm 471, San Francisco, Ca 94132-1722
Grant 5SC2MH086071-03 from National Institute Of General Medical Sciences
Abstract: Increasingly, human neurological diseases are being mapped to genome regions shared between affected individuals, however current methods generally identify large genomic regions containing many genes. For example, Williams-Beuren Syndrome (WBS), results in learning deficits and cardiopulmonary phenotypes and is associated with deletion of at least 25 genes in the 1.5 Mb WBS critical region (WBSCR). Interestingly, those affected with WBS often have a ´hyper-gregarious´ nature and enhanced language or music skills. Despite the small number of genes implicated, the lack of a social animal model has limited the study of how WBSCR genes affect social interaction and little is known about the WBSCR genes or how they contribute to the characteristic WBS symptoms. Social insects, including ants and bees, are a tractable experimental system to test the in vivo effects of WBSCR genes on complex social behaviors. We propose to perturb the expression level of genes from the WBSCR in the social insect, Linepithema humile (Argentine ant). We will 1) Use comparative genomics to identify WBSCR gene orthologs in several genomes and annotate their exons, regulatory elements, and repeats. 2) Develop L. humile cDNA and fosmid resources to clone, sequence, and assess the methylation state of WBSCR gene regions. 3) Use RNA interference constructs to perturb expression of WBSCR genes in ants and observe changes in individual and group behaviors. In addition to these research objectives, the principal investigator will pursue the following developmental goals with the guidance of his mentor, Dr. Gary Karpen 4) establish an independent research group 5) enhance personal mentoring and teaching skills 6) improve the quality of research. Relevance to Public Health Social interaction is a complex behavior that profoundly affects human health and well-being. Experimentation with behavior genes in humans is not feasible, making the development of a ´social behavior´ animal model system desirable. The proposed studies will elucidate the conserved protein, cis-DNA regulatory features, and gene networks involved in Williams-Beuren Syndrome and will develop a social animal model system to test other gene-behavior interactions. This study of WBSCR genes promises to identify novel biomarkers and gene targets for therapeutic intervention of behavioral disorders
Keywords: Affect; Animal Model; Animal Models and Related Studies; Ants; Assay; Bees; Behavior; Behavior Disorders; Behavioral; Beuren syndrome; Bio-Informatics; Bioassay; Biochemical; Bioinformatics; Biologic Assays; Biological Assay; Biological Models; Cardiopulmonary; Characteristics; Chromosome 7; Chromosomes, Human, Pair 7; Complementary DNA; Complex; Contiguous Gene Syndrome, Williams; Coupled; DNA Molecular Biology; DNA, Complementary; Depression; Development; Disease; Disorder; Educational process of instructing; Elfin Facies Syndrome; Exhibits; Exons; Fanconi Schlesinger syndrome; Fanconi-Schlesinger syndrome; Gene Targeting; Genes; Genes, Regulator; Genetic; Genome; Genomics; Goals; Health; Hostility; Human; Human, General; Hymenoptera; Individual; Insecta; Insects; Invertebrates, Insects; Language; Learning; Link; Literature; Man (Taxonomy); Man, Modern; Maps; Mental Depression; Mentors; Methods; Methylation; Model System; Models, Biologic; Molecular; Molecular Biology; Music; Musics; Nature; Nervous System Diseases; Neurologic; Neurologic Disorders; Neurological; Neurological Disorders; Ortholog; Orthologous Gene; Personal Satisfaction; Phenotype; Post-Transcriptional Gene Silencing; Post-Transcriptional Gene Silencings; Posttranscriptional Gene Silencing; Posttranscriptional Gene Silencings; Principal Investigator; Promoter; Promoters (Genetics); Promotor; Promotor (Genetics); Protein Methylation; Proteins; Psyche structure; Public Health; Quelling; RNA Interference; RNA Silencing; RNA Silencings; RNAi; RT-PCR; RTPCR; Regulator Genes; Regulatory Element; RegulatoryElement; Research; Research Resources; Resources; Reverse Transcriptase Polymerase Chain Reaction; Sequence-Specific Posttranscriptional Gene Silencing; Social Behavior; Social Interaction; Symptoms; System; System, LOINC Axis 4; Targetings, Gene; Teaching; Testing; Therapeutic Intervention; Transcriptional Regulatory Elements; Vertebrate Animals; Vertebrates; Williams Barratt syndrome; Williams Syndrome; Williams syndrome (WMS, WS); Williams-Barratt syndrome; Williams-Beuren Syndrome; Williams-Beuren syndrome (WBS); Work; behavioral disorder; biomarker; cDNA; comparative; comparative genomics; disease/disorder; elfin-facies hypercalcemia syndrome; experience; gene product; hypercalcemia-peculiar facies-supravalvular aortic stenosis syndrome; hypercalcemia/Williams-Beuren syndrome; idiopathic hypercalcemia-supravalvular aortic stenosis syndrome; improved; in vivo; intervention therapy; mental; mental retardation-typical facies-aortic stenosis syndrome; model organism; nervous system disorder; neurological disease; novel; prevent; preventing; public health medicine (field); regulatory gene; reverse transcriptase PCR; skills; social; social integration; sociobehavior; sociobehavioral; trans acting element; vertebrata; well-being
Project start date: 2008-09-16
Project end date: 2011-07-31
Budget start date: 1-AUG-2010
Budget end date: 31-JUL-2011
PFA/PA: PAR-06-492
5SC2MH086071-03 (2010): $115125
Sponsored Links Excellgen http://Excellgen.com
ARGENTINE ANTS: A SYSTEM A STUDY GENES INVOLVED IN HUMAN BEHAVIORAL DISEASE
Christopher David Smith
San Francisco State University, 1600 Holloway Ave, Adm 471, San Francisco, Ca 94132-1722
Grant 5SC2MH086071-02 from National Institute Of General Medical Sciences
Abstract: Increasingly, human neurological diseases are being mapped to genome regions shared between affected individuals, however current methods generally identify large genomic regions containing many genes. For example, Williams-Beuren Syndrome (WBS), results in learning deficits and cardiopulmonary phenotypes and is associated with deletion of at least 25 genes in the 1.5 Mb WBS critical region (WBSCR). Interestingly, those affected with WBS often have a ´hyper-gregarious´ nature and enhanced language or music skills. Despite the small number of genes implicated, the lack of a social animal model has limited the study of how WBSCR genes affect social interaction and little is known about the WBSCR genes or how they contribute to the characteristic WBS symptoms. Social insects, including ants and bees, are a tractable experimental system to test the in vivo effects of WBSCR genes on complex social behaviors. We propose to perturb the expression level of genes from the WBSCR in the social insect, Linepithema humile (Argentine ant). We will 1) Use comparative genomics to identify WBSCR gene orthologs in several genomes and annotate their exons, regulatory elements, and repeats. 2) Develop L. humile cDNA and fosmid resources to clone, sequence, and assess the methylation state of WBSCR gene regions. 3) Use RNA interference constructs to perturb expression of WBSCR genes in ants and observe changes in individual and group behaviors. In addition to these research objectives, the principal investigator will pursue the following developmental goals with the guidance of his mentor, Dr. Gary Karpen 4) establish an independent research group 5) enhance personal mentoring and teaching skills 6) improve the quality of research. Relevance to Public Health Social interaction is a complex behavior that profoundly affects human health and well-being. Experimentation with behavior genes in humans is not feasible, making the development of a ´social behavior´ animal model system desirable. The proposed studies will elucidate the conserved protein, cis-DNA regulatory features, and gene networks involved in Williams-Beuren Syndrome and will develop a social animal model system to test other gene-behavior interactions. This study of WBSCR genes promises to identify novel biomarkers and gene targets for therapeutic intervention of behavioral disorders
Keywords: Affect; Animal Model; Animal Models and Related Studies; Ants; Assay; Bees; Behavior; Behavior Disorders; Behavioral; Beuren syndrome; Bio-Informatics; Bioassay; Biochemical; Bioinformatics; Biologic Assays; Biological Assay; Biological Models; Cardiopulmonary; Characteristics; Chromosome 7; Chromosomes, Human, Pair 7; Complementary DNA; Complex; Contiguous Gene Syndrome, Williams; Coupled; DNA Molecular Biology; DNA, Complementary; Development; Disease; Disorder; Educational process of instructing; Elfin Facies Syndrome; Exhibits; Exons; Fanconi Schlesinger syndrome; Fanconi-Schlesinger syndrome; Gene Targeting; Genes; Genes, Regulator; Genetic; Genome; Genomics; Goals; Health; Hostility; Human; Human, General; Hymenoptera; Individual; Insecta; Insects; Invertebrates, Insects; Language; Learning; Link; Literature; Man (Taxonomy); Man, Modern; Maps; Mentors; Methods; Methylation; Model System; Models, Biologic; Molecular; Molecular Biology; Music; Musics; Nature; Nervous System Diseases; Neurologic; Neurologic Disorders; Neurological; Neurological Disorders; Ortholog; Orthologous Gene; Personal Satisfaction; Phenotype; Post-Transcriptional Gene Silencing; Post-Transcriptional Gene Silencings; Posttranscriptional Gene Silencing; Posttranscriptional Gene Silencings; Principal Investigator; Promoter; Promoters (Genetics); Promotor; Promotor (Genetics); Protein Methylation; Proteins; Psyche structure; Public Health; Quelling; RNA Interference; RNA Silencing; RNA Silencings; RNAi; RT-PCR; RTPCR; Regulator Genes; Regulatory Element; RegulatoryElement; Research; Research Resources; Resources; Reverse Transcriptase Polymerase Chain Reaction; Sequence-Specific Posttranscriptional Gene Silencing; Social Behavior; Social Interaction; Symptoms; System; System, LOINC Axis 4; Targetings, Gene; Teaching; Testing; Therapeutic Intervention; Transcriptional Regulatory Elements; Vertebrate Animals; Vertebrates; Williams Barratt syndrome; Williams Syndrome; Williams syndrome (WMS, WS); Williams-Barratt syndrome; Williams-Beuren Syndrome; Williams-Beuren syndrome (WBS); Work; behavioral disorder; biomarker; cDNA; comparative; depression; disease/disorder; elfin-facies hypercalcemia syndrome; experience; gene product; hypercalcemia-peculiar facies-supravalvular aortic stenosis syndrome; hypercalcemia/Williams-Beuren syndrome; idiopathic hypercalcemia-supravalvular aortic stenosis syndrome; improved; in vivo; intervention therapy; mental; mental retardation-typical facies-aortic stenosis syndrome; model organism; nervous system disorder; neurological disease; novel; prevent; preventing; public health medicine (field); regulatory gene; reverse transcriptase PCR; skills; social; social integration; sociobehavior; sociobehavioral; trans acting element; vertebrata; well-being
Project start date: 2008-09-16
Project end date: 2011-07-31
Budget start date: 1-AUG-2009
Budget end date: 31-JUL-2010
PFA/PA: PAR-06-492
5SC2MH086071-02 (2009): $115125
Grants awarded to Christopher David Smith
Argentine Ants: A System A Study Genes Involved In Human Behavioral Disease
Christopher David Smith
Biologysan Francisco State University
1600 Holloway Ave, Adm 471
san Francisco, Ca 941321722
Grant 1SC2MH086071-01 from National Institute Of Mental Health IRG: ZGM1
Abstract: Increasingly, human neurological diseases are being mapped to genome regions shared between affected individuals, however current methods generally identify large genomic regions containing many genes. For example, Williams-Beuren Syndrome (WBS), results in learning deficits and cardiopulmonary phenotypes and is associated with deletion of at least 25 genes in the 1.5 Mb WBS critical region (WBSCR). Interestingly, those affected with WBS often have a ´hyper-gregarious´ nature and enhanced language or music skills. Despite the small number of genes implicated, the lack of a social animal model has limited the study of how WBSCR genes affect social interaction and little is known about the WBSCR genes or how they contribute to the characteristic WBS symptoms. Social insects, including ants and bees, are a tractable experimental system to test the in vivo effects of WBSCR genes on complex social behaviors. We propose to perturb the expression level of genes from the WBSCR in the social insect, Linepithema humile (Argentine ant). We will 1) Use comparative genomics to identify WBSCR gene orthologs in several genomes and annotate their exons, regulatory elements, and repeats. 2) Develop L. humile cDNA and fosmid resources to clone, sequence, and assess the methylation state of WBSCR gene regions. 3) Use RNA interference constructs to perturb expression of WBSCR genes in ants and observe changes in individual and group behaviors. In addition to these research objectives, the principal investigator will pursue the following developmental goals with the guidance of his mentor, Dr. Gary Karpen 4) establish an independent research group 5) enhance personal mentoring and teaching skills 6) improve the quality of research. Relevance to Public Health Social interaction is a complex behavior that profoundly affects human health and well-being. Experimentation with behavior genes in humans is not feasible, making the development of a ´social behavior´ animal model system desirable. The proposed studies will elucidate the conserved protein, cis-DNA regulatory features, and gene networks involved in Williams-Beuren Syndrome and will develop a social animal model system to test other gene-behavior interactions. This study of WBSCR genes promises to identify novel biomarkers and gene targets for therapeutic intervention of behavioral disorders
Project start date: 2008-09-16
Project end date: 2011-07-31
1SC2MH086071-01 (2008): $114813