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MicroRNA functions in single cells

Objective

It is now becoming apparent that genes are regulated not only by transcription, but also by thousands of post-transcriptional regulators that can stabilize or degrade mRNAs. Some of the most important regulators are miRNAs, short RNA molecules that are deeply conserved in sequence and are involved in numerous biological processes, including human disease. Surprisingly, transcriptomic and proteomic studies show that most miRNAs only have subtle silencing effects on their targets, suggesting additional important, but yet undiscovered functions. Thus the question is raised: if the main function of miRNAs is not to silence targets, what is it?

I will test two novel hypotheses about miRNA function. The first hypothesis proposes that miRNAs can buffer gene expression noise. The second hypothesis is inspired by my preliminary results and proposes that miRNAs can synchronize expression of genes. If I validate either hypothesis, it would mean that miRNA functions can be investigated in entirely new ways, yielding important new biological insights relevant to both basic research and human health. However, these hypotheses can only be tested in individual cells, and the necessary single-cell technologies and computational tools are only maturing now.

I will apply my expertise in miRNA biology and in combined wet-lab and computational methods to design, develop and apply miRCell-seq to test these two hypotheses in cell cultures and in animals. This new method will for the first time measure miRNAs, their targets, and the interactions between them in single cells and transcriptome-wide. We will use mutant cells devoid of miRNAs and time course experiments to generate sufficient data to develop detailed models of the miRNA impact on their targets. We will then validate our findings with single cell proteomics. This project thus has the potential to reveal novel functions of miRNAs and substantially improve our general understanding of gene regulation.

Fields of science (EuroSciVoc)

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Keywords

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Programme(s)

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Topic(s)

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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-STG - Starting Grant

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Call for proposal

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(opens in new window) ERC-2017-STG

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Host institution

STOCKHOLMS UNIVERSITET
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 497 650,02
Address
UNIVERSITETSVAGEN 10
10691 Stockholm
Sweden

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Region
Östra Sverige Stockholm Stockholms län
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.

€ 1 497 650,02

Beneficiaries (1)

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