Deciphering sumoylation-dependent signalling through systematic loss-of-function analysis in C. elegans

蛋白质通常在多蛋白复合物中具有活性，并且必须定位到适当的细胞区室中。在许多情况下，蛋白质被修饰，这些修饰可以调节它们的稳定性，促进物理相互作用并指定它们的定位。一种这样的修饰是SUMO化;其中短多肽（SUMO）被转移到蛋白质上。蛋白质上添加的SUMO导致新的相互作用或重新定位。SUMO化与亨廷顿病和病毒感染有关。一些病毒抑制类小泛素化以创造更好的增殖环境。我发现在没有SUMO的情况下，致癌途径，与癌症有关的途径，更加活跃。 我将研究sumoylation在体内系统鉴定的辅因子参与这一过程中使用C。优雅的模特该模型的优点是类小泛素化过程在C.有一种叫做RNA干扰（RNAi）的技术可以使基因表达失活。我们已经建立了一个RNAi文库，可以单独灭活C.线虫基因组利用这项技术，我将确定基因的合作和调节sumoylation过程。我还将使用经典的生物化学和荧光成像来可视化亚细胞定位。

Proteins are often active in multiprotein complexes and have to be localised into the appropriate cellular compartments. In many cases, proteins are modified and these modifications can regulate their stability, promote physical interactions and specify their localisation, for example. One such modification is sumoylation; where a short polypeptide (SUMO) is transferred onto a protein. The added SUMO on a protein leads to novel interactions or relocalisation. Sumoylation has been found involved in Huntington‘s disease and viral infection. Some viruses inhibit sumoylation to create a better environment for their multiplication. I discovered that in absence of SUMO, oncogenic pathways, pathways involved in cancer, are more active. I will investigate sumoylation in vivo by systematic identification of the co-factors involved in this process using C. elegans as a model. The advantages of this model are that the sumoylation process is conserved in C. elegans, and there is a technology called RNA interference (RNAi) that inactivates gene expression. We have built an RNAi library that individually inactivates all the predicted genes of the C. elegans genome. Using this technology I will identify the genes cooperating and regulating the sumoylation process. I will also use classical biochemistry and fluorescence imaging to visualise sub-cellular localisation.