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Born 23 April 1968 Email: mihaela.zavolan@unibas.ch |
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Past Research The emergence of high-throughput technologies has changed the way biological problems are approached. Sophisticated computational methods applied to large-scale datasets of sequences and expression profiles allow one to now simultaneously study the response of many genes and biological pathway to developmental and environmental stimuli. My first contribution in computational biology was an analysis of the spectrum of mutations that took place during somatic hypermutation of immunoglobulin genes and during evolution of pseudogenes, which lead to the hypothesis of a two-tiered mechanism underlying somatic hypermutation. Experimental data in support of this model has recently started to emerge. I have then participated in a number of studies of large-scale sequence data generated at the Riken Institute. My contributions were to show that alternative splicing is very frequent in mouse, that alternative exons differ from constitutive ones in a number of regulatory sequence motifs, and that alternative transcription start sites can be coupled with the changes in downstream splicing. Since I have established my group at the Biozentrum in Basel, we have focused to a large extent on small regulatory RNAs. We have contributed to the discovery of virus-encoded miRNAs, of many mammalian miRNAs, and of the principles of miRNA-target recognition. Currently, we are investigating the regulation of mRNA metabolism by small RNAs and RNA-binding proteins. |
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Current projects Our current aim is to understand the role of various post-transcriptional regulatory mechanisms under normal conditions, particularly in development, and in disease. Through transcriptomics and proteomics approaches we are studying the function of specific miRNAs in development and cancers. By combining crosslinking and immunprecipitation with deep sequencing and computational modeling, we aim to understand how RNA-binding proteins recognize their target and how the interplay of multiple RNA-binding proteins on individual mRNAs determines the lifetime and protein output of these mRNAs. Many of the factors that we are studying exhibit specific patterns of deregulation in diseases such as cancers, and we therefore hope that our studies will shed light on the contribution of post-transcriptional regulatory mechanisms to the process of cell division, particularly under pathological conditions. |
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| Research within the Node | |
| One of the aims of Cellplasticity is to understand the patterns of gene expression along various developmental lineages. These patterns are set by a combination of epigenetic, transcription and post-transcriptional factors. Ideally, one would like to build quantitative models that relate the sequence of a gene (including promoter, enhancers, genomic neighborhood, transcript 3'UTR, etc.) to the gene's expression in a particular context. Towards this goal we will contribute our expertise in the regulation at the RNA level. Interestingly, Not surprisingly, post-transcriptional regulators can act on factors that regulate the chromatin state, thereby having broad consequences on transcriptional events Preliminary data from a variety of groups also indicate that miRNAs play important roles in development and differentiation, partly because they regulate the translation of transcription factors. | |
Sinkkonen L, Hugenschmidt T, Berninger P, Gaidatzis D, Mohn F, Artus-Revel CG, Zavolan M, Svoboda P, Filipowicz W. (2008) MicroRNAs control de novo DNA methylation through regulation of transcriptional repressors in mouse embryonic stem cells. Nat Struct Mol Biol. 15:259-67.
Aravin A, Gaidatzis D, Pfeffer S, Lagos-Quintana M, Landgraf P, Iovino N, Morris P, Brownstein MJ, Kuramochi-Miyagawa S, Nakano T, Chien M, Russo JJ, Ju J, Sheridan R, Sander C, Zavolan M, Tuschl T. (2006) A novel class of small RNAs bind to MILI protein in mouse testes. Nature 442:203-207.
Chern T-M, van Nimwegen E, Kai C, Kawai J, Carninci P, Hayashizaki Y, Zavolan M. (2006) A simple physical model predicts small exon-length variations. PLoS Genetics 2:e45.
Pfeffer S, Sewer A, Lagos-Quintana M, Sheridan R, Sander C, Grasser FA, van Dyk LF, Chien M, Russo JJ, Ju J, Randall G, Lindenbach BD, Rice CM, Simon V, Ho DD, Zavolan M, Tuschl T. Identi?cation of the microRNAs of the herpesvirus family. Nature Methods 2:269-276 (2005).