2004-05-012024-05-18https://scholars.lib.ntu.edu.tw/handle/123456789/712978摘要：細胞進行計劃性的凋亡(programmed cell death, apoptosis,以下簡稱細胞凋亡)對多細胞生物體的發育以及組織恆定性的維持(tissue homeostasis)扮演非常重要的角色。細胞凋亡失控時與癌症以及功能退變(degeneration)等疾病的發生息息相關。細胞凋亡後的細胞屍體會由吞噬細胞或鄰近細胞進行吞噬作用將之除去，此一吞噬死細胞的步驟必須被嚴格的監控，因為吞噬作用太過會造成功能退變等疾病，太少則會造成自體免疫疾病，最近的研究更發現吞噬作用會刺激細胞的凋亡，由此可見吞噬死細胞對細胞凋亡與生物體的發育和正常生長極為重要。線蟲(C. elegans)全身透明，細胞凋亡可在活體中直接觀察，我們計畫以線蟲作為模式動物，利用便利且有效的RNA干擾技術(RNA interference)來搜尋鑑定參與吞噬死細胞過程的重要基因。由目前的pilot screen，我們發現ina-1 與rtk-x基因當被RNA干擾技術去活化後，會影響吞噬作用的發生，顯示我們RNAi的搜尋方法具有高度的可行性與成功性。此外，初步的遺傳分析發現ina-1與rtk-x作用於兩個不同的路徑(各<br> Abstract: Programmed cell death (apoptosis) is important for metazoan development and tissue homeostasis. Abnormality in apoptosis has been implicated in cancer and degeneration diseases. Cells that die by programmed cell death are engulfed and eliminated. The engulfment process is of important medical relevance, as too little engulfment has been implicated in autoimmune diseases and too much engulfment in degeneration diseases. Recent finding in the nematode C. elegans shows that the engulfment process does not only remove cell corpses passively but also actively promotes apoptosis. Moreover, despite of their importance, genes that function in the engulfment process have been difficult to isolate using the mammalian cell cultured systems. The nematode C. elegans has been a leading model for genetic and molecular analysis of cell death. Here, we take the advantage of simplicity and powerful RNA interference (RNAi) methods developed in C. elegans to identify genes that act in the engulfment of programmed cell death. In a pilot RNAi screen we identified ina-1 and rtk-x that act in the engulfment process, indicating that our screen is feasible and promising. Combining powerful molecular and genetics tools and sensitive cell death assays available in C. elegans, we aim to characterize genes identified in the screen including ina-1 and rtk-x in detail. Our preliminary results indicate that ina-1 and rtk-x act in two distinct pathways mediated by ced-1 and ced-2, respectively. We believe that further characterization of these two genes in C. elegans will shed light on the mechanism of cell-corpse engulfment during programmed cell death. As studies have shown that molecules made up of the death machinery are evolutionarily conserved, we will extend our studies to humans and further understand how human homologs of these genes function to control the engulfment process of apoptosis.線蟲細胞凋亡吞噬作用Programmed cell deathapoptosisengulfmentC. elegans