PhD Position at IECB, Bordeaux, France

A Grad Student Position is available in the Laboratory of Dr. Dupuy at the European Institute of Chemistry and Biology / Institut Europeen de Chimie et Biologie (IECB). The institute was founded in 1998 in Bordeaux (France) and hosts diverse and international groups covering a wide range of scientific interests.

Integrative spatiotemporal analysis of gene regulation during C. elegans post embryonic development.

It has recently been shown that one can evaluate the impact of miRNA regulation on a given gene by comparing the expression patterns obtained from a transcriptional fusion with a generic UTR to monitor transcriptional activity, and another including the cognate UTR. The goal here will be to scale up the approach to investigate miRNA regulation in a systematic and quantitative manner. Indeed to date most miRNA targets have been identified computationally and lack experimental confirmation. We will apply an iterative strategy in which we will initially characterize the expression patterns of a few regulators and all their predicted targets. Then, we will identify the complete list of potential regulators for each of these targets and characterize their respective transcription patterns.

Thirty to forty genes are predicted to be regulated by let-7 miRNA in C. elegans genome. For each of these genes we will generate transgenic animals expressing GFP under the control of the corresponding proximal promoter with and without the cognate UTR. For each pair of reporter constructs we will assess quantitative differences in tissue specific expression on whole animals population using the COPAS profiling system (Dupuy et al, 2007). In this case, we will confirm that the difference in gene expression is related to the presence of the let-7 miRNA by comparing the let-7 promoter expression pattern with that of its putative targets.

Most UTRs are predicted to be the target of more than one miRNA. Based on published miRNA targets prediction one can estimate that forty to fifty distinct miRNAs are also involved in the posttranscriptional regulation of messenger RNAs targeted by let-7. We will characterize the expression patterns of all the other potential regulators of let-7 targets, by generating transgenic animals carrying the corresponding promoter::GFP constructs. Integrating the expression patterns of a set of miRNAs and their putative targets throughout post-embryonic development will make it possible to dissect the relative contributions of the various miRNAs on a given messenger translation.

The position is starting September 2008 and funding is in place to support the salary for three years.

Please send your letter of motivation, CV and letters of reference directly to Dr. Denis Dupuy.