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NascenTomiX SIGNED

Ribosome inhibition by nascent or antimicrobial peptides

Total Cost €

0

EC-Contrib. €

0

Partnership

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 NascenTomiX project word cloud

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

types    coding    sensors    rely    ribosomal    precisely    molecule    complementary    molecular    natural    technique    small    during    explaining    sense    sequence    peptide    entire    position    naturally    arrested    sensing    protein    maps    action    acid    exit    handle    inhibitory    interacting    function    weight    form    characterization    inverse    inhibit    gene    fundamental    translational    subunit    arrest    details    mrna    perform    insights    yielded    tunnel    groundbreaking    code    nascent    precise    occurring    translation    point    occasionally    mediated    molecules    nature    regulators    region    synthesis    amino    eukaryotes    unexplored    regulation    diversity    structural    act    ribosome    peptides    depends    consolidator    governing    primarily    expression    dependent    genetic    trans    biochemical    ligand    mode    decipher    stalling    toeprinting    bacteria    designing    retaining    metabolite    group    bases    antibiotics    largely    generation    chain    erc   

Project "NascenTomiX" data sheet

The following table provides information about the project.

Coordinator
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE 

Organization address
address: RUE DE TOLBIAC 101
city: PARIS
postcode: 75654
website: www.inserm.fr

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 France [FR]
 Total cost 1˙999˙125 €
 EC max contribution 1˙999˙125 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-COG
 Funding Scheme ERC-COG
 Starting year 2017
 Duration (year-month-day) from 2017-06-01   to  2022-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE FR (PARIS) coordinator 1˙999˙125.00

Map

 Project objective

During the translation of genetic information into protein by the ribosome, nascent peptides occasionally inhibit their own synthesis by interacting with the exit tunnel of the large ribosomal subunit. Known as nascent chain-mediated translational arrest, this process depends primarily upon the amino acid sequence of the arrest peptide. However, it can also rely upon the sensing of a low molecular weight ligand by the ribosome nascent chain complex, explaining its use for metabolite-dependent gene regulation in both bacteria and eukaryotes. Biochemical and structural studies of arrest peptides have yielded key insights into their mode of action, but their ability to sense different types of small molecules, their impact as regulators of gene expression in nature and the precise molecular details behind the arrest process are still largely unexplored. The groundbreaking aim of this ERC Consolidator research program is to decipher the arrest code governing nascent chain-mediated translational arrest in bacteria. My approach will be based on a technique recently developed in my group, referred to here as inverse toeprinting, which precisely maps the position of an arrested ribosome nascent chain complex on the mRNA while retaining the entire peptide-coding region up to the point of stalling.

The overall aim will be achieved through four complementary objectives: (i) to assess the extent to which arrest peptides can act as small molecule sensors; (ii) to identify naturally occurring arrest peptides in bacteria; (iii) to develop trans-inhibitory peptides that target the ribosome; and (iv) to perform the structural characterization of new ribosome inhibitory peptides.

By addressing the natural diversity and molecular bases of the arrest process, this project will be the key to understanding a unique form of gene regulation and a fundamental aspect of ribosome function. It will also provide a handle for designing next-generation antibiotics.

 Publications

year authors and title journal last update
List of publications.
2018 Justine Charon, Aitor Manteca, C. Axel Innis
Using the Bacterial Ribosome as a Discovery Platform for Peptide-Based Antibiotics
published pages: 75-84, ISSN: 0006-2960, DOI: 10.1021/acs.biochem.8b00927
Biochemistry 58/2 2020-02-06
2018 Mario Mardirossian, Natacha Pérébaskine, Monica Benincasa, Stefano Gambato, Sven Hofmann, Paul Huter, Claudia Müller, Kai Hilpert, C. Axel Innis, Alessandro Tossi, Daniel N. Wilson
The Dolphin Proline-Rich Antimicrobial Peptide Tur1A Inhibits Protein Synthesis by Targeting the Bacterial Ribosome
published pages: 530-539.e7, ISSN: 2451-9456, DOI: 10.1016/j.chembiol.2018.02.004
Cell Chemical Biology 25/5 2019-05-23
2018 Britta Seip, Guénaël Sacheau, Denis Dupuy, C Axel Innis
Ribosomal stalling landscapes revealed by high-throughput inverse toeprinting of mRNA libraries
published pages: e201800148, ISSN: 2575-1077, DOI: 10.26508/lsa.201800148
Life Science Alliance 1/5 2019-05-23

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