WHYMIR

Interplays between miRNAs and transcription factors in the determination and maintenance of cell identity

 Coordinatore UNIVERSITAET BASEL 

Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.

 Nazionalità Coordinatore Switzerland [CH]
 Totale costo 891˙759 €
 EC contributo 891˙759 €
 Programma FP7-IDEAS-ERC
Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
 Code Call ERC-2012-StG_20111109
 Funding Scheme ERC-SG
 Anno di inizio 2012
 Periodo (anno-mese-giorno) 2012-11-01   -   2015-10-31

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    UNIVERSITAET BASEL

 Organization address address: Petersplatz 1
city: BASEL
postcode: 4003

contact info
Titolo: Dr.
Nome: Kurt
Cognome: Kamber
Email: send email
Telefono: +41 61 2672833

CH (BASEL) hostInstitution 891˙759.00
2    UNIVERSITAET BASEL

 Organization address address: Petersplatz 1
city: BASEL
postcode: 4003

contact info
Titolo: Prof.
Nome: Mihaiela Luxita
Cognome: Zavolan
Email: send email
Telefono: +41 61 267 15 77
Fax: +41 61 267 15 85

CH (BASEL) hostInstitution 891˙759.00

Mappa


 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

transcriptional    mrna    induced    function    gene    small    tfs    expression    affecting    mirna    immunoprecipitation    directly    their    cell    genes    reprogramming    mirnas    cells    somatic   

 Obiettivo del progetto (Objective)

'miRNAs are small RNAs that guide the RNA-induced silencing complex to mRNA targets, destabilizing them and inhibiting their translation. Much has been learned about their involvement in organism development and function, yet some striking puzzles remain. On the one hand it has been shown that miRNAs are essential for development, and the preferential targeting of transcription factors (TFs) by miRNAs suggests that miRNAs and TFs 'coordinate' to regulate gene expression. Furthermore, studies in the past year concluded that, on their own or in combination with TFs, miRNAs can induce reprogramming of somatic cells into induced pluripotent stem cells (iPSC). On the other hand, high-throughput measurements of mRNA and protein level changes upon miRNA transfections suggest that miRNAs have largely a 'fine-tuning' function. These small effects on individual genes must, however, confer a substantial selective advantage, because many target sites remain conserved over long evolutionary distances. Here I first propose to investigate the hypothesis that instead of primarily affecting the average levels of target genes, miRNAs reduce the cell-to-cell variation in gene expression, affecting precisely the steps that determine the intrinsic noise. I will then use miRNA-mediated reprogramming of somatic cells into iPSCs as a model system to directly investigate the 'coordination' between miRNAs and TFs in determining cell identity and differentiation. Through determination of miRNA targets with Argonaute crosslinking and immunoprecipitation, mRNA sequencing and methylated DNA immunoprecipitation I attempt to retrace the regulatory interactions that lead from induction of a few miRNAs, through perturbation of TF activities, to the activation of 'stemness' genes. Finally, following up on preliminary results obtained in my lab, I will investigate the function of miRNA targeting in the nucleus, that potentially couples transcriptional and post-transcriptional regulation more directly.'

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