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Content archived on 2024-06-18

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

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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Topic(s)

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Call for proposal

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ERC-2012-StG_20111109
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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-SG - ERC Starting Grant

Host institution

UNIVERSITAT BASEL
EU contribution
€ 891 759,00
Address
PETERSPLATZ 1
4051 Basel
Switzerland

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Region
Schweiz/Suisse/Svizzera Nordwestschweiz Basel-Stadt
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

No data

Beneficiaries (1)

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