Untersuchungen zur Hangover Funktion während der Entwicklung von Alkoholtoleranz und der zellulären Stressantwort

目的是了解细胞应激途径如何引起神经元适应的变化，以及这些变化如何反过来促进乙醇诱导的行为。之前我们已经在果蝇中发现了宿醉突变体。这个突变体对乙醇的耐受性降低。通过对宿醉突变体的表型和分子遗传学分析，我们已经表明，对乙醇的行为反应在分子水平上与细胞对高温和氧化应激的应激反应部分相似，并且涉及宿醉基因（Scholz et al., 2005）。现在需要解决的关键问题是，这些缺陷是发育性的还是由细胞对乙醇的应激反应直接引起的；确定耐受所需的宿醉蛋白的生化活动；确定可能的相互作用伙伴；确定宿醉调节的靶基因。通过这些分析，我们希望深入了解宿醉在细胞水平上促进耐受性发展的机制。

The goal is to understand how a cellular stress pathway might cause changes in neuronal adaptation and how these changes in turn contribute to ethanol induced behavior. Previously we have identified the hangover mutant in Drosophila. This mutant develops reduced ethanol tolerance. By phenotypic and molecular genetic analyzing the hangover mutants we have shown that the behavioral response to ethanol is on the molecular level similar in part similar to a cellular stress response to heat and oxidative stress and involves the hangover gene (Scholz et al., 2005). Key questions to address now are whether the defects are developmental or directly caused by a cellular stress response to ethanol, to define the biochemical activities of the Hangover protein that are required for tolerance, to identify possible interaction partners and to identify target genes that are regulated by Hangover. With these analyses we want to gain insight into the mechanism by which Hangover acts on the cellular level to promote the development of tolerance.