Exploring at the single molecule level the functional consequences of disease-causing mutations in the human RNA processing factor LRPPRC

19 May 2023
Job Information

Organisation/Company

UNIVERSITE CLERMONT AUVERGNE

Research Field

Chemistry » Biochemistry
Biological sciences » Biology
Physics

Researcher Profile

Recognised Researcher (R2)
Leading Researcher (R4)
First Stage Researcher (R1)
Established Researcher (R3)

Country

France

Application Deadline

25 Jun 2023 – 22:00 (UTC)

Type of Contract

Temporary

Job Status

Full-time

Offer Starting Date

1 Oct 2023

Is the job funded through the EU Research Framework Programme?

Not funded by an EU programme

Is the Job related to staff position within a Research Infrastructure?

No

Offer Description

Numerous mitochondrial disorders, predominantly affecting muscular and neuronal tissues, are caused by pathogenic variants in nuclear-encoded genes coding for mitochondrial DNA (mtDNA) replication, expression, and RNA processing factors. Most of these mutations have been found in factors involved in mitochondrial transcription, mRNA processing and stabilization (LRPPRC, SLIRP). The LRPPRC/SLIRP complex has been suggested to regulate mRNA stability by changing it secondary structure, however, the mechanisms involved are not yet known. Moreover, whereas a mutation in the LRPPRC gene was identified as one of the first nuclear mitochondrial disease genes, mutations in SLIRP causing mitochondrial encephalomyopathy were identified only last year. Despite a renewed interest in mtDNA due to its involvement in human disease and ageing, there are still many fundamental questions surrounding faithful expression and RNA processing of mtDNA. Establishing the molecular details of how defects in these processes contribute to human disease constitutes a major challenge. This PhD proposal intends to answer some of these questions, and, more specifically, to decipher the RNA remodeling role of the LRPPRC/SLIRP complex and its disease-causing variants. For this purpose, we will use a combination of classical biochemistry tools and innovative single molecule biophysical techniques. The expected results will significantly increase our understanding of the mechanisms of transcription regulation by the LRPPRC/SLIRP complex. Normal and pathogenic variants of the proteins will be directly compared, giving insight in the mechanistic basis of the associated disorders.

Funding category: Contrat doctoral

PHD title: Doctorat de Biologie
PHD Country: France

Requirements
Specific Requirements

Nous recherchons une personne motivée, intéressée par la multidisciplinarité et l'international

 

Prérequis: classement dans la première moitié du M2 et moyenne au M2 supérieure à 12

Anglais nécessaire

Additional Information
Work Location(s)

Number of offers available

1

Company/Institute

UNIVERSITE CLERMONT AUVERGNE

Country

France

City

Clermont Ferrand

Where to apply

Website

https://www.abg.asso.fr/fr/candidatOffres/show/id_offre/114564

Contact

Website

https://www.uca.fr/

STATUS: EXPIRED