Currently, there are two ongoing projects in the lab:

    1) Modelling cancer in Caenorhabditis elegans 
    2) Functional Genomics of Spliceosome  components 

Beside the great interest for the basic science, these two projects may contribute  to future clinical applications because:

(i) RNAi screens and C. elegans genetics could identify “synthetic lethal” or “modifiers” genes of cancer related genes, and those genes may be diagnostic markers or ideal drug targets against cancer.

(ii) There is an extremely high level of conservation between splicing proteins in nematodes and humans. Thus, a “functional map” of Spliceosome components in C. elegans will be a valuable resource for a better understanding of how alterations in the levels of different types of RNA may lead to several diseases, including cancer.

1) Modelling cancer in Caenorhabditis elegans

As different diseases are controlled and human life span increase, cancer is becoming one of the main causes of human mortality. Cancer is a complex disease that is being studied from diverse perspectives. There are more than 300 genes that have been implicated in human cancer. While the cancer census is still growing, functional studies are becoming more essential and necessary to discover how the combination of these gene expression alterations affects tumorigenesis. By using C. elegans Genetics and Genomics tools (mutants, transgenic strains, RNAi libraries..etc...) we are creating Functional maps, which are going beyond the description of a single gene function by correlating such function with other genes, phenotypes or expression patterns. We are currently working with SWI/SNF chromatin remodelling subunits that have been implicated in cancer–related processes. Ultimately, we intend to add novel nodes and links within cancer gene networks.

2) Functional Genomics of spliceosome components

There is an increasing amount of data pointing to additional functional roles of splicing related proteins. To address this issue we are currently building a functional genomics map of Splicing-related components or Spliceosome components.First, combining genomic information available in web-based resources, we are generating the platform to assemble a “Spliceosome functional map” in C. elegans. This information includes description of gene functions in genome-wide RNAi screens (Phenome), large-scale identification of protein-protein interactions (Interactome), extensive characterization of expression profiles (Localizome) and microarray-based mRNA expression studies to obtain transcriptional profiles (Transcriptome). Moreover, We are extending the “Phenome” data by doing a detailed description of RNAi phenotypes, at different developmental stages and at different lineages (GFP labeled). To achieve that aim, we have created a collection of RNAi clones to inactivate 164 C. elegans genes orthologs to human spliceosome genes (Barbosa-Morais et al, 2006) that will be used to our functional genomic analysis. Due to the high level of conservation between splicing factors in nematodes and human, this approach will provide a valuable resource for a better understanding of how molecules and pathways interrelate in the control of gene expression, and how alterations in the splicing proteins functions may lead to disease.