GENES WITH MAJOR EFFECTS ON LIFE SPAN IN C ELEGANS

描述(改编自申请人的摘要)：线虫 秀丽线虫饥饿或过度拥挤的条件可能会激活 一种发育开关，因此达尔幼虫，一个发育中的 被捕获的、非喂食的动物被生产出来。过去的调查显示 确定了两种达尔结构性突变，这两种突变导致动物 在大量食物存在的情况下形成达尔幼虫，并有达尔缺陷 在正常诱导下防止Dauer形成的突变 条件。近年来，温度敏感的达尔构成等位基因 基因daf-2的作用已被证明可以延长成年人的寿命(和 通过daf-16基因的Dauer缺陷突变来预防)。 此外，daf-12和daf-23的突变也会影响这一过程。 本提案的目标是了解特定的daf基因是如何 影响寿命，并利用这些基因来理解分子和 决定寿命的生理过程。重点 将放在对daf-2和daf-12基因的分析上。这个 两个基因的完整序列和表达模式将是 在后面的实验中特别强调地确定了 确定特定细胞对寿命是否重要 决心。下游靶标或基因与之相互作用或受其调控 这些基因也将被寻找。

DESCRIPTION (Adapted from the applicant's abstract): In the nematode Caenorhabditis elegans starvation or overcrowded conditions may activate a developmental switch so that the dauer larvae, a developmental arrested, non- feeding animal, is produced. Past investigations have identified both dauer- constitutive mutations, which cause animals to form dauer larvae in the presence of abundant food, and dauer-defective mutations, which prevent dauer formation under normal inducing conditions. Recently, temperature-sensitive dauer-constitutive alleles of the gene daf-2 have been shown to prolong adult lifespan (and be prevented by dauer-defective mutations in the gene daf-16). Additionally, mutations in daf-12 and daf-23 also affect this process. The goal of the present proposal is to understand how specific daf genes affect life span and to use these genes to understand the molecular and physiological processes that underlie life span determination. Emphasis will be placed on the analysis of the daf-2 and daf-12 genes. The complete sequences and patterns of expressions of both genes will be determined with particular emphasis in the latter experiments to ascertain whether specific cells are important for life-span determination. Downstream targets or genes interacting with or regulated by these genes will also be sought.