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MtbTransReg SIGNED

Translational regulation in the persistence and drug susceptibility of Mycobacterium tuberculosis

Total Cost €

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EC-Contrib. €

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Partnership

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 MtbTransReg project word cloud

Explore the words cloud of the MtbTransReg project. It provides you a very rough idea of what is the project "MtbTransReg" about.

susceptibility    decades    switch    cutting    mechanisms    cure    molecules    re    shine    central    latent    selectively    few    signals    protein    coli    drug    differential    leaderless    selective    edge    hypothesis    unexpected    transcriptome    urgent    bacterial    emergence    ribosomes    fundamental    mrnas    bacteria    sequences    generally    disease    leader    poorly    gene    paradigms    viewed    initiation    correlations    translation    search    preferential    rational    infection    interaction    transcripts    optimise    escherichia    causes    establishing    human    stress    modify    replicating    tuberculosis    copies    lack    techniques    sd    persistence    persist    treatments    combined    demonstrated    mrna    quantitative    dalgarno    profiles    data    cell    context    bioinformatic    underlying    canonical    contain    biology    contributes    regulation    shape    resistance    asymptomatic    translated    proteome    mycobacterium    experimental    sequence    expresses    resistant    determined    suggest    specialised   

Project "MtbTransReg" data sheet

The following table provides information about the project.

Coordinator
LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE ROYAL CHARTER 

Organization address
address: KEPPEL STREET
city: LONDON
postcode: WC1E 7HT
website: http://www.lshtm.ac.uk/

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country United Kingdom [UK]
 Project website https://blogs.lshtm.ac.uk/corteslab/research-2/
 Total cost 1˙495˙625 €
 EC max contribution 1˙495˙625 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-STG
 Funding Scheme ERC-STG
 Starting year 2015
 Duration (year-month-day) from 2015-06-01   to  2021-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE ROYAL CHARTER UK (LONDON) coordinator 1˙495˙625.00

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 Project objective

Mycobacterium tuberculosis causes human tuberculosis but can also persist for decades as an asymptomatic latent infection. The mechanisms underlying persistence are poorly understood, and the emergence of drug-resistant tuberculosis makes the development of effective new treatments an urgent challenge. Understanding the ability of M. tuberculosis to switch between replicating and non-replicating states during infection and disease is central to the search for improved treatments. The number of copies of a protein produced by a cell is generally viewed as being determined by the number of mRNA transcripts, but recent findings suggest that ‘specialised ribosomes’ can modify proteome profiles by preferential translation of particular mRNA subsets, particularly in response to stress. mRNA molecules contain specific signals that optimise their interaction with ribosomes; known as leader sequences, these include the Shine-Dalgarno (SD) sequence required for canonical translation initiation in bacteria. I recently demonstrated that M. tuberculosis expresses an unexpected number of leaderless mRNA transcripts that lack the SD sequence. In Escherichia coli, only a few leaderless transcripts have been described and they are selectively translated by specialised ribosomes. I propose to test the hypothesis that differential translation of mRNA subsets contributes to M. tuberculosis persistence and drug susceptibility. I will investigate the importance of selective translation of leaderless and SD mRNAs in the context of adaptation to stress and drug resistance in M. tuberculosis, using cutting-edge experimental techniques combined with bioinformatic analyses. The proposed project addresses the fundamental systems biology challenge of establishing quantitative correlations between transcriptome and proteome data, and beyond contributing to the rational design of novel treatments to cure tuberculosis, could help to re-shape classical paradigms of bacterial gene regulation.

 Publications

year authors and title journal last update
List of publications.
2019 Dimitrios Evangelopoulos, Gareth A. Prosser, Angela Rodgers, Belinda M. Dagg, Bhagwati Khatri, Mei Mei Ho, Maximiliano G. Gutierrez, Teresa Cortes, Luiz Pedro S. de Carvalho
Comparative fitness analysis of D-cycloserine resistant mutants reveals both fitness-neutral and high-fitness cost genotypes
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-019-12074-z
Nature Communications 10/1 2020-02-04
2019 Álvaro Chiner-Oms, Michael Berney, Christine Boinett, Fernando González-Candelas, Douglas B. Young, Sebastien Gagneux, William R. Jacobs, Julian Parkhill, Teresa Cortes, Iñaki Comas
Genome-wide mutational biases fuel transcriptional diversity in the Mycobacterium tuberculosis complex
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-019-11948-6
Nature Communications 10/1 2020-01-24
2018 Elizabeth B Sawyer, Anna D Grabowska, Teresa Cortes
Translational regulation in mycobacteria and its implications for pathogenicity
published pages: 6950-6961, ISSN: 0305-1048, DOI: 10.1093/nar/gky574
Nucleic Acids Research 46/14 2020-01-24
2017 Teresa Cortes, Olga T. Schubert, Amir Banaei-Esfahani, Ben C. Collins, Ruedi Aebersold, Douglas B. Young
Delayed effects of transcriptional responses in Mycobacterium tuberculosis exposed to nitric oxide suggest other mechanisms involved in survival
published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-017-08306-1
Scientific Reports 7/1 2020-01-24

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