{"id":4840,"date":"2014-06-03T10:19:03","date_gmt":"2014-06-03T14:19:03","guid":{"rendered":"https:\/\/web.uri.edu\/inbre\/?page_id=4840"},"modified":"2014-06-03T10:19:03","modified_gmt":"2014-06-03T14:19:03","slug":"stillwell","status":"publish","type":"page","link":"https:\/\/web.uri.edu\/riinbre\/research\/ecd\/stillwell\/","title":{"rendered":"A drosophila model of ALS"},"content":{"rendered":"<p><strong>Investigator:<\/strong>\u00a0Geoff Stillwell, Rhode Island College<\/p>\n<p><strong>Mentor:<\/strong>\u00a0Robert Reenan, Brown University<\/p>\n<p><strong>Scientific Theme:<\/strong>\u00a0Neuroscience &amp; Molecular Toxicology<\/p>\n<p style=\"text-align: justify\"><strong>Abstract:\u00a0<\/strong>Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease that causes progressive\u00a0motor neuron degeneration and leads to muscle weakness and death in afflicted individuals. The average\u00a0survival time is 3 years after diagnosis and Riluzole, the only approved therapeutic, shows minimal increases\u00a0in survival time. Familial forms of the disease produce similar or identical pathologies and have been used\u00a0extensively to model the human disease state. Mutations in the superoxide dismutase 1 (SOD1) were first\u00a0described 20 years ago and more than 150 mutations in this gene have been documented in patients to\u00a0date. In well-characterized mouse SOD models, disease pathogenesis appear to be a consequence of\u00a0protein aggregation; however, it is still unclear which cellular and molecular changes are considered critical\u00a0and relevant to ALS pathogenesis due to significant phenotypic variability in the animal models combined\u00a0with the non-physiological expression levels of mutant SOD protein.<\/p>\n<p style=\"text-align: justify\">To address the issue of variability within the genetic models and to address questions relating to pathogenic\u00a0events, we will develop and characterize novel ALS models using homologous recombination to insert\u00a0disease-associated mutations into the endogenous SOD gene of the genetically tractable model organism\u00a0Drosophila melanogaster. The overall objective of this program is to create and characterize a series of\u00a0mutant SOD alleles within a single isogenic background to allow for direct comparisons between alleles and\u00a0characterize the resulting biological events leading to toxicity. As a first specific aim, we will first use\u00a0homologous recombination to \u2018knock-in\u2019 two SOD mutations that exhibit seemly differential toxicity and\u00a0characterize the effects in flies. As a second aim, will conduct forward genetic screens to identify enhancers\u00a0of toxicity and use methods developed previously to adapt this model for well-based high-throughput\u00a0screening in vivo screening to identify chemical suppressors of toxicity. This research will enhance\u00a0collaborations between investigators at Brown University and Rhode Island College.<\/p>\n<p style=\"text-align: justify\"><strong>Human Health Relevance:<\/strong>\u00a0This proposal aims to investigate the events leading to motor neuron death in Amyotrophic Lateral Sclerosis\u00a0in a translational model that could also be used to find new drug targets and therapeutic compounds. This\u00a0project represents collaborative efforts between scientists at Rhode Island College and Brown University and\u00a0will provide undergraduates at Rhode Island College the opportunity to engage in translational research.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Investigator:\u00a0Geoff Stillwell, Rhode Island College Mentor:\u00a0Robert Reenan, Brown University Scientific Theme:\u00a0Neuroscience &amp; Molecular Toxicology Abstract:\u00a0Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease that causes progressive\u00a0motor neuron degeneration and leads to muscle weakness and death in afflicted individuals. The average\u00a0survival time is 3 years after diagnosis and Riluzole, the only approved therapeutic, shows minimal increases\u00a0in [&hellip;]<\/p>\n","protected":false},"author":1036,"featured_media":0,"parent":10203,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"page-twocol.php","meta":{"_acf_changed":false,"footnotes":"","_links_to":"","_links_to_target":""},"class_list":["post-4840","page","type-page","status-publish","hentry"],"acf":[],"_links":{"self":[{"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/pages\/4840","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/users\/1036"}],"replies":[{"embeddable":true,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/comments?post=4840"}],"version-history":[{"count":0,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/pages\/4840\/revisions"}],"up":[{"embeddable":true,"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/pages\/10203"}],"wp:attachment":[{"href":"https:\/\/web.uri.edu\/riinbre\/wp-json\/wp\/v2\/media?parent=4840"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}