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MYCOCHASSIS SIGNED

Engineering of a minimal bacterial therapeutic chassis

Total Cost €

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EC-Contrib. €

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Partnership

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Project "MYCOCHASSIS" data sheet

The following table provides information about the project.

Coordinator
FUNDACIO CENTRE DE REGULACIO GENOMICA 

Organization address
address: CARRER DOCTOR AIGUADER 88
city: BARCELONA
postcode: 8003
website: www.crg.es

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 Spain [ES]
 Total cost 2˙454˙522 €
 EC max contribution 2˙454˙522 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-ADG
 Funding Scheme ERC-ADG
 Starting year 2015
 Duration (year-month-day) from 2015-11-01   to  2020-10-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    FUNDACIO CENTRE DE REGULACIO GENOMICA ES (BARCELONA) coordinator 2˙454˙522.00

Map

 Project objective

Engineering bacteria to deliver therapeutic agents or to present antigens for vaccination is an emerging area of research with great clinical potential. The most challenging issue in this field is the selection of the right bacteria to engineer, commonly known as “chassis”. The best chassis depends on the application but there is a common drawback in bacteria used nowadays: their complexity and the lack of quantitative information for many reactions which limits genome engineering to classical trial and error approaches. In this project, we want to engineer the genome-reduced bacterium M. pneumoniae using a whole-cell model that will drive the rational to create a chassis for human and animal therapy. Its small size (816 Kbases), the lack of cell wall, and the vast amount of comprehensive quantitative –omics datasets makes this bacterium one of the best candidates for chassis design. By combining bioinformatics, -omics, and biochemistry approaches with genome engineering tools, systems biology analyses, and computational whole-cell models, MYCOCHASSIS aims to: i) develop a whole cell-model based on organism-specific experimental data that will be validated experimentally and that can predict the impact of genome modifications; ii) implement genome engineering tools to delete non-essential pathogenic and virulent elements predicted by the whole-cell model to engineer a therapeutical chassis; iii) using the whole-cell model design and engineer genes and circuits to improve growth rate in a defined medium. iv) as a proof of concept introduce orthogonal gene circuits to secrete peptides and enzymes capable of dissolving in vitro biofilms made by the lung pathogens Pseudomonas aeruginosa and Staphylococus aureus. This project will validate the usefulness of whole-cell models for synthetic biology by modelling multiple genomic modifications orientated to facilitate engineering of biological systems.

 Publications

year authors and title journal last update
List of publications.
2015 M. Lluch-Senar, J. Delgado, W.-H. Chen, V. Llorens-Rico, F. J. O\'Reilly, J. A. Wodke, E. B. Unal, E. Yus, S. Martinez, R. J. Nichols, T. Ferrar, A. Vivancos, A. Schmeisky, J. Stulke, V. van Noort, A.-C. Gavin, P. Bork, L. Serrano
Defining a minimal cell: essentiality of small ORFs and ncRNAs in a genome-reduced bacterium
published pages: 780-780, ISSN: 1744-4292, DOI: 10.15252/msb.20145558
Molecular Systems Biology 11/1 2019-07-05
2016 Ivan Junier, E.?Besray Unal, Eva Yus, Ver?nica Llor?ns-Rico, Luis Serrano
Insights into the Mechanisms of Basal Coordination of Transcription Using a Genome-Reduced Bacterium
published pages: 391-401, ISSN: 2405-4712, DOI: 10.1016/j.cels.2016.04.015
Cell Systems 2/6 2019-07-05
2015 V. Llorens-Rico, M. Lluch-Senar, L. Serrano
Distinguishing between productive and abortive promoters using a random forest classifier in Mycoplasma pneumoniae
published pages: 3442-3453, ISSN: 0305-1048, DOI: 10.1093/nar/gkv170
Nucleic Acids Research 43/7 2019-07-05
2016 Wei-Hua Chen, Vera van?Noort, Maria Lluch-Senar, Marco L. Hennrich, Judith A. H.?Wodke, Eva Yus, Andreu Alib?s, Guglielmo Roma, Daniel R. Mende, Christina Pesavento, Athanasios Typas, Anne-Claude Gavin, Luis Serrano, Peer Bork
Integration of multi-omics data of a genome-reduced bacterium: Prevalence of post-transcriptional regulation and its correlation with protein abundances
published pages: 1192-1202, ISSN: 0305-1048, DOI: 10.1093/nar/gkw004
Nucleic Acids Research 44/3 2019-07-05
2015 Maria Lluch-Senar, Luca Cozzuto, Jaime Cano, Javier Delgado, Ver?nica Ll?rens-Rico, Sabine Pereyre, C?cile Bebear, Luis Serrano
Comparative ?-omics? in Mycoplasma pneumoniae Clinical Isolates Reveals Key Virulence Factors
published pages: e0137354, ISSN: 1932-6203, DOI: 10.1371/journal.pone.0137354
PLOS ONE 10/9 2019-07-05
2016 V. Llorens-Rico, J. Cano, T. Kamminga, R. Gil, A. Latorre, W.-H. Chen, P. Bork, J. I. Glass, L. Serrano, M. Lluch-Senar
Bacterial antisense RNAs are mainly the product of transcriptional noise
published pages: e1501363-e150136, ISSN: 2375-2548, DOI: 10.1126/sciadv.1501363
Science Advances 2/3 2019-07-05
2017 Marie Trussart, Eva Yus, Sira Martinez, Davide Baù, Yuhei O. Tahara, Thomas Pengo, Michael Widjaja, Simon Kretschmer, Jim Swoger, Steven Djordjevic, Lynne Turnbull, Cynthia Whitchurch, Makoto Miyata, Marc A. Marti-Renom, Maria Lluch-Senar, Luís Serrano
Defined chromosome structure in the genome-reduced bacterium Mycoplasma pneumoniae
published pages: 14665, ISSN: 2041-1723, DOI: 10.1038/ncomms14665
Nature Communications 8 2019-07-05
2016 Maria Lluch-Senar, Francesco M. Mancuso, H?ctor Climente-Gonz?lez, Marcia I. Pe?a-Paz, Eduard Sabido, Luis Serrano
Rescuing discarded spectra: Full comprehensive analysis of a minimal proteome
published pages: 554-563, ISSN: 1615-9853, DOI: 10.1002/pmic.201500187
PROTEOMICS 16/4 2019-07-05
2015 M. Trussart, F. Serra, D. Bau, I. Junier, L. Serrano, M. A. Marti-Renom
Assessing the limits of restraint-based 3D modeling of genomes and genomic domains
published pages: 3465-3477, ISSN: 0305-1048, DOI: 10.1093/nar/gkv221
Nucleic Acids Research 43/7 2019-07-05
2017 Eva Yus, Jae-Seong Yang, Adrià Sogues, Luis Serrano
A reporter system coupled with high-throughput sequencing unveils key bacterial transcription and translation determinants
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-017-00239-7
Nature Communications 8/1 2019-05-04
2017 Samuel Miravet-Verde, Verónica Lloréns-Rico, Luis Serrano
Alternative transcriptional regulation in genome-reduced bacteria
published pages: 89-95, ISSN: 1369-5274, DOI: 10.1016/j.mib.2017.10.022
Current Opinion in Microbiology 39 2019-05-04

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