Genetic Studies of Gene Silencing in Drosophila

RNA干扰(RNAi)是一种通过双链RNA控制基因表达的自然机制。与双链触发器同源的信使RNA被酶破坏。这一机制提供了对病毒的内源性保护和转座元件的动员。细胞凋亡涉及细胞死亡，并参与正常的发育过程。在初步实验中，发现细胞死亡会导致相邻细胞中RNAi的抑制。据推测，来自垂死细胞的信号导致了这种抑制。为了深入了解细胞死亡信号抑制RNAi的机制，本项目将在果蝇中进行突变，以确定通过白色眼色基因的RNAi抑制沉默的突变。这些已确定的突变将被用来试图理解细胞死亡信号抑制RNAi的分子机制。通过绘制基因图谱并从基因组序列中确定预测的基因，修饰基因的收集将提供有关相关分子过程的信息。细胞死亡是与发育有关的自然过程，其抑制可能导致癌症。RNA干扰也是基因沉默的自然过程，可以起到保护病毒的作用。细胞死亡被发现抑制了相邻扇区的RNA干扰过程。如果病毒感染攻克了RNAi的第一道防线，并杀死了一个细胞，这种相互作用可能就是这种情况。濒临死亡的细胞可能会向其邻居发送信号，以诱导更有效的抗病毒机制，与RNA干扰过程竞争。这个项目将研究这种相互作用的机制。该研究项目还将有助于指导一名博士后，并将参与科学研究的本科生介绍给他们。

RNA interference (RNAi) is a natural mechanism involved with the control of gene expression that operates via double stranded RNA. Homologous messenger RNAs to the double stranded trigger are enzymatically destroyed. This mechanism provides an endogenous protection against viruses and transposable element mobilization. Apoptosis involves cell death and is involved with normal developmental processes. In preliminary experiments, it was found that cell death would cause inhibition of RNAi in adjacent cells. It is hypothesized that signals from the dying cells cause this inhibition. In order to gain insight into the mechanism of inhibition of RNAi by cell death signaling, this project will involve a mutagenesis in Drosophila to identify mutations that modify the inhibition of silencing via RNAi of the white eye color gene. The mutations identified will be used in an attempt to understand the molecular mechanism of inhibition of RNAi by cell death signaling. By mapping the genes and determining the predicted genes from the genomic sequence, the collection of modifier genes will provide information about the molecular processes involved.Cell death is a natural process involved with development and its inhibition can lead to cancer. RNA interference is also a natural process of gene silencing that can serve as a protection against viruses. Cell death was found to inhibit the process of RNA interference in adjacent sectors. This interaction might be the case if a viral infection overcomes the first line of defense of RNAi and kills a cell. The dying cell might send signals to its neighbors to induce more potent antiviral mechanisms that compete with the RNA interference process. This project will investigate the mechanism of this interaction. The research project will also contribute to the mentoring of a postdoctoral fellow and introduce the undergraduates involved to scientific research.