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Mapping functional protein-RNA interactions to identify new targets for oligonucleotide-based therapy

Objective

An important question of modern neurobiology is how neurons regulate synaptic function in response to excitation. In particular, the roles of alternative pre-mRNA splicing and mRNA translation regulation in this response are poorly understood. We will study the RNA-binding proteins (RBPs) that control these post-transcriptional changes using a UV crosslinking-based purification method (CLIP) and ultra-high throughput sequencing. Computational analysis of the resulting data will define the sequence and structural features of RNA motifs recognized by each RBP. Splicing microarrays and translation reporter assays will then allow us to examine the regulatory functions of RBPs and RNA motifs. By integrating the biochemical and functional datasets, we will relate the position of RNA motifs to the activity of bound RBPs, and predict the interactions that act as central nodes in the regulatory network. The physiological role of these core RBP-RNA interactions will then be tested using antisense RNAs. Together, these projects will provide insights to the regulatory mechanisms underlying neuronal activity-dependent changes, and provide new opportunities for future treatments of neurodegenerative disorders.

Field of science

  • /natural sciences/biological sciences/genetics and heredity/rna
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins
  • /natural sciences/biological sciences/neurobiology

Call for proposal

ERC-2007-StG
See other projects for this call

Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

University College London
Address
Gower Street
WC1E 6BT London
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 80 923,20
Principal investigator
Jernej Ule (Dr.)
Administrative Contact
Malgorzata Kielbasa (Ms.)

Beneficiaries (3)

University College London
United Kingdom
EU contribution
€ 80 923,20
Address
Gower Street
WC1E 6BT London
Activity type
Higher or Secondary Education Establishments
Principal investigator
Jernej Ule (Dr.)
Administrative Contact
Malgorzata Kielbasa (Ms.)
UNIVERZA V LJUBLJANI
Slovenia
EU contribution
€ 144 000
Address
Kongresni Trg 12
1000 Ljubljana
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Jasna Bevk (Ms.)
MEDICAL RESEARCH COUNCIL

Participation ended

United Kingdom
EU contribution
€ 675 076,80
Address
North Star Avenue Polaris House 2 Floor David Phillips Building
SN2 1FL Swindon
Activity type
Research Organisations
Administrative Contact
Elizabeth Cutler (Ms.)