Other projects:

Project 1

Project 2

Project 3

fig1

Figure 1: Regulation of miRNA expression. The expression of miRNAs can be monitored by multiple methods including quantitative RT-PCR (qRT-PCR) or by examined the expression of GFP when fused to the promoter of our miRNAs of interest. We are examining how pertubations to the environments or mutations to genes critical to the regulation of the animal's response to environmental stress affect the expression of aging-associated miRNAs.

Project 4:

Regulators of miRNAs

We previously reported that miRNAs that are upregulated during aging in C. elegans can function during lifespan and stress resistance in the nematode (de Lencastre et al, 2010). In order to understand the molecular mechanisms underlying miRNA function in these biological processes, we are studying what upstream factors might be responsible for miRNA upregulation and function during adulthood (Figure 1). Using the Mod-Encode project, which characterized the occupancy of numerous transcription factors across promoter regions in C. elegans, we are testing whether mutations to these candidate protein regulators cause differential expression of our aging associated miRNAs. In addition, we are using an unbiased approach (Figure 2) to identify potential upstream regulators of miRNA expression from an RNAi library. The regulation of miRNA expression in response to stress has been noted in several organisms (Figure 3). Similarities between the expression patterns observed across phyla suggest that principles discovered in C. elegans may be broadly useful in identification of corresponding regulatory systems of miRNA mediated stress response in higher eukaryotes.


Fig3

Figure 3: The regulation of miRNA expression in response to stress is conserved across species.

Fig2

Figure 2: Genetic screen for regulators of miRNA expression. In order to identify regulators of miRNA expression, we will screen an RNAi library containing ~16,000 C. elegans genes for their effect on the expression of GFP reporters of miR-71 and miR-239 expression. We expect that RNAi constructs that target regulators of these miRNAs will lead to altered spatial or temporal expression of miRNA::GFP expression helping us to understand the biological network and cell localization that utilize miRNA signalling.