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

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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.