Phone: +43 1 79730
Research Group: www.imp.ac.at/groups/luisa-cochella
Institution: Research Institute of Molecular Pathology (IMP)
Full member of the Focus Regulatory RNA (SFB RNA Reg) since 2015 and of the DoktoratsKolleg (DK) RNA Biology since 2017.
PhD students within/associated to the DK:
Paula Gutierrez Perez
DK RNA Biology Alumni:
Chiara Alberti: “Dissecting the contribution of microRNAs to nervous system development and function in C. elegans”
For complete list of group members please visit the Cochella group website.
Spatio-temporal specificity of miRNA biogenesis and function
As a single-cell zygote divides and its daughters continue to do so, the patterns of gene expression in each cell change due to intrinsic and external cues. These changes in gene expression have been primarily studied at the transcriptional level, with a number of transcription factor and chromatin associated proteins being implicated in driving many of the changes required for the developmental process. However, the role of post-transcriptional regulation in this process is much less understood. We are currently studying how transcriptional and post-transcriptional mechanisms integrate into gene regulatory networks that define different cell types during development. We are also interested in how the different mechanisms of gene regulation have contributed to the evolution of cell-type complexity.
With the discovery of microRNAs, short RNAs that can act as specific repressors of gene expression at the post-transcriptional level, we have a very good entry point to understand the impact of post-transcriptional regulation of gene expression to development and evolution. To do so, we use as a model system the nematode Caenorhabditis elegans, which is well known for the availability of extremely powerful genetic tools for its study. But in addition, C. elegans offers an invariant body plan where the lineage history and identity of every one of its ~950 cells – as well as a lot about the function of every cell – is known. Moreover, a growing group of Caenorhabditis sp. as well as other out groups have had their genomes fully sequenced and are also tractable with genetic approaches, making these species useful for comparative studies. Together, this makes “the worms” ideally suited model organisms to ask our questions of interest.
Combining genetic approaches, next generation sequencing and in vivo strategies that allow us to follow miRNA expression and function with single-cell resolution, we are currently dissecting the roles of miRNAs in providing specific cell types with their functional properties. We have found that many miRNAs are themselves expressed with very high spatio-temporal specificity, with an extreme case being a miRNA that is made and acts in a single neuron out of the 302 neurons that make up the C. elegans nervous system. This not only allows us to generate hypotheses about the roles of these miRNAs during cell-type specification but also leads us into understanding how their expression is regulated and therefore how this class of regulators is integrated in the cascade of events that unfolds from that totipotent one-cell zygote.
Selected publications: (since 2015)
Cell-type specific sequencing of microRNAs from complex animal tissues.
Alberti C, Manzenreither RA, Sowemimo I, Burkard TR, Wang J, Mahofsky K, Ameres SL, Cochella L.
Nat Methods. 2018 Apr;15(4):283-289.
A framework for understanding the roles of miRNAs in animal development.
Alberti C, Cochella L.
Development. 2017 Jul 15;144(14):2548-2559.
Neuron type-specific miRNA represses two broadly expressed genes to modulate an avoidance behavior in C. elegans.
Drexel T, Mahofsky K, Latham R, Zimmer M, Cochella L.
Genes Dev. 2016 Sep 15;30(18):2042-2047.