Skip to main content

Mechanisms of microRNA biogenesis and turnover

Objective

MicroRNAs (miRNAs) are a novel class of genes, accounting for >1% of genes in a typical animal genome. They constitute an important layer of gene regulation that affects diverse processes such as cell differentiation, apoptosis, and metabolism. Despite such critical roles, deciphering the mechanism of action of miRNAs has been difficult, leading to multiple, partially contradictory, models of miRNA activity. Moreover, adding an additional layer of complexity, it is now emerging that miRNA activity is regulated by various mechanisms that we are only beginning to identify. Our objective is to understand how miRNAs are regulated under physiological conditions, in the roundworm Caenorhabditis elegans. We will focus on pathways of miRNA turnover, an issue of fundamental importance that has received little attention because miRNAs are widely held to be highly stable molecules. However, miRNA over-accumulation causes aberrant development and disease, prompting us to test rigorously whether degradation can antagonize miRNA activity and either identify the machinery involved, or confirm the dominance of other regulatory modalities, whose components we will identify. C. elegans is the organism in which miRNAs and many components of the miRNA machinery were discovered. However, previous studies emphasized genetics and cell biology approaches, limiting the degree of mechanistic insight that could be obtained. In addition to exploiting the traditional strengths of C. elegans, we will therefore develop and apply biochemical and genomic techniques to obtain a comprehensive understanding of miRNA regulation, enabling us to demonstrate both molecular mechanisms and physiological relevance. Given the importance of miRNAs in development and disease, identifying the regulators of these tiny gene regulators will be both of scientific interest and biomedical relevance.

Field of science

  • /natural sciences/biological sciences/genetics and heredity/genome
  • /natural sciences/biological sciences/cell biology

Call for proposal

ERC-2009-StG
See other projects for this call

Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH FONDATION
Address
Maulbeerstrasse 66
4058 Basel
Switzerland
Activity type
Research Organisations
EU contribution
€ 1 782 200
Principal investigator
Helge Grosshans (Dr.)
Administrative Contact
Dorothy Searles (Mrs.)

Beneficiaries (2)

FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH FONDATION
Switzerland
EU contribution
€ 1 782 200
Address
Maulbeerstrasse 66
4058 Basel
Activity type
Research Organisations
Principal investigator
Helge Grosshans (Dr.)
Administrative Contact
Dorothy Searles (Mrs.)
Novartis Forschungsstiftung
Switzerland
Address
Maulbeerstrasse 66
4058 Basel
Activity type
Research Organisations
Administrative Contact
Dorothy Searles (Mrs.)