Modelling cancer in Caenorhabditis elegans (canceromics)
Modelling cancer in Caenorhabditis elegans
Start date: Oct 1, 2007,
End date: Mar 31, 2012
Cancer is a complex disease that results from accumulation of diverse alterations in the genome. There are more than 300 genes identified as “cancer genes” although it is estimated that there are many more involved in cancer development that could be significant during tumorigenesis and putative targets for drugs therapies. Several scientific groups are performing a comprehensive sequencing of genes in cancer cells but these studies lack of functional validation. Since cancer requires the combination of several defects in the genome, an organism amenable for genetics and functional genomics studies as Caenorhabditis elegans would provide the ideal platform to identified those fatidic combinations. I plan to take advantage of C. elegans mutants and a “RNA interference” (RNAi) library to uncover functions and pathways of the following C. elegans genes: A) SWI/SNF complex subunit ZK1128.5 baf-60: The SWI/SNF complex is conserved from yeast to humans and acts in chromatin remodelling to regulate gene expression. baf-60 mutants present extra proliferation at particular lineages. B) Claspin, F25H5.5: Human Claspin acts as a DNA damage checkpoint through the activation of chk1 protein kinase. chk-1 also acts as a DNA damage checkpoint in C. elegans. I have preliminary results in C. elegans pointing to a novel role of Claspin in genome stability. C) Spliceosome (or splicing-related) components rsr-2 and lsm-2: I have recently published that rsr-2 and lsm-2 act in the RAS pathway that determine the vulval cell fate in C. elegans (Ceron et al, 2007). This observation and others suggests functional relationships between spliceosome-related genes and cancer. The discovery of functional networks for these genes will contribute to create a “Functional map for cancer genes” that will be a essential toward understanding this complex disease and, ultimately, find effective therapies.
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