Non-canonical nucleoside incorporation into synthetic RNA-oligonucleotides: investigations towards the discovery of selective RNA-binding proteins

Información del proyecto

OLIGOBINPRO

Identificador del acuerdo de subvención: 659339

DOI

10.3030/659339

Proyecto finalizado el 28 Febrero 2017

Fecha de la firma de la CE 12 Marzo 2015

Fecha de inicio 1 Junio 2015

Fecha de finalización 31 Mayo 2017

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total

€ 159 460,80

Aportación de la UE

€ 159 460,80

Coordinado por

LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Germany

Objetivo

The increase of life expectancy around the world comes at the unavoidable cost of a rise in the occurrence of neurological diseases such as Parkinson’s as well as debilitating ones like cancer. These conditions prevent the possibility of a sustained quality of life and cost society vast amounts of money for the treatment and care of patients. It is the responsibility of scientists to find innovative methods of treating and eliminating these diseases, allowing for a healthier quality of life. Recently, RNA-binding proteins have been linked to biological processes leading to these diseases as well as the expression of genes relating to obesity. A plethora of natural chemical modifications in RNA fine-tune its structure, allowing for this specific interaction which regulates processes such as gene expression and the tuning of translation. Although these have been known for years, their binding proteins have not been systematically studied. The difficulty of the chemical synthesis of modified oligoribonucleotides represents the major bottleneck in this field. The overall aim of this project is to discover RNA-binding proteins which bind to the non-canonical modifications Am, Cm, Gm, i6A and ms2i6A which were identified in the mRNA of human cancer cell lines. These will first be synthesised and then incorporated into oligoribonucleotide strands mimicking natural mRNA. By incubating with cellular extracts, we subsequently aim to identify their binding proteins by tagging them with novel technologies and analysing them using mass spectrometric techniques. This project will inspire and offer unique training to Dr. Michaelides by exposing him to this multidisciplinary field where chemistry and biology meet, enabling him to embark on his own academic career. Furthermore, it will set the foundation for the better understanding of the mechanisms responsible for the aforementioned conditions, which will in the long term lead to the design of new therapies for their prevention.

Ámbito científico (EuroSciVoc)

• ciencias naturales › ciencias biológicas › bioquímica › biomoléculas › proteínas › proteómica
• ciencias médicas y de la salud › medicina clínica › oncología
• ciencias naturales › ciencias biológicas › genética › ARN
• ciencias médicas y de la salud › medicina básica › neurología › parkinson
• ciencias médicas y de la salud › ciencias de la salud › nutrición › obesidad

Palabras clave

• non-canonical nucleosides
• oligonucleotides
• RNA-binding proteins
• bioorthogonal chemistry

Programa(s)

• H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions PROGRAMA PRINCIPAL
  
• H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
  

Tema(s)

• MSCA-IF-2014-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF)
  

Régimen de financiación

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

Convocatoria de propuestas

H2020-MSCA-IF-2014

Coordinador

LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN

• Aportación neta de la UEn: € 159 460,80
• Dirección: GESCHWISTER SCHOLL PLATZ 1 ; 80539 MUNCHEN ; Alemania
• Región: Bayern › Oberbayern › München, Kreisfreie Stadt
• Tipo de actividad: Higher or Secondary Education Establishments
• Coste total: € 159 460,80