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Cyclic Di-GMP signaling in cell behavior and reproduction (Bonus of excellence)
| Project funded by own resources |
| Project title |
Cyclic Di-GMP signaling in cell behavior and reproduction (Bonus of excellence) |
| Principal Investigator(s) |
Jenal, Urs
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| Project Members |
Emming, Stefan
de Jong, Imke
Lori, Christian
Hug, Isabelle
Steiner, Samuel
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| Organisation / Research unit |
Departement Biozentrum / Molecular Microbiology (Jenal) |
| Project start |
01.04.2013 |
| Probable end |
31.03.2016 |
| Status |
Completed |
| Abstract |
Lay summary: Pathogenic and non-pathogenic bacteria exist in two fundamentally different life styles, a single cell, free-living, so-called planktonic state and a multicellular, surface adherent and matrix embedded state, which is generally referred to as biofilms. In pathogens, biofilms are generally associated with reduced virulence and increased persistence mechanisms, which allow bacteria to counter and survive the attacks by the host immune system and by antimicrobial agents during chronic infections. Bacterial biofilms are the primary cause of chronic infections and of resulting infection relapses. To be able to interfere with bacterial persistence it is vital to understand the molecular details of biofilm formation and to define how motile planktonic cells transit into surface-grown communities. The nucleotide second messenger cyclic di-guanosinemonophosphate (c-di-GMP) has emerged as a central regulatory factor governing bacterial surface adaptation and biofilm formation. Although c-di-GMP signaling may well represent the Achilles heel of bacterial communities, c-di-GMP networks in bacterial pathogens are exquisitely complex and an integrated cellular system to uncover the details of cdGMP dynamics is missing. To quantitatively describe cdGMP signaling we propose to exploit Caulobacter crescentus, an organism with a simple bimodal life-style that integrates the sessile-motile switch into its asymmetric division cycle. We aim to: 1) identify the role and regulation of all diguanylate cyclases and phosphodiesterases that contribute to the asymmetric cellular program with the goal to model the temporal and spatial distribution of cdGMP during development; 2) identify and characterize c-di-GMP effectors, their downstream targets and cellular pathways; 3) elucidate how c-di-GMP coordinates cell differentiation with cell growth and propagation; 4) unravel the role of c-di-GMP as an allosteric regulator in mechanosensation and in rapid adaptation of bacteria to growth on surfaces. We propose a multidisciplinary research program at the forefront of bacterial signal transduction that will provide the molecular and conceptual framework for a rapidly growing research field of second messenger signaling in pathogenic bacteria. |
| Financed by |
Other funds
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Cooperations () |
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ID |
Kreditinhaber |
Kooperationspartner |
Institution |
Laufzeit - von |
Laufzeit - bis |
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2291915 |
Jenal, Urs |
Pfohl, Thomas, Professor |
Departement Chemie, University of Basel |
01.04.2013 |
31.03.2016 |
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2291919 |
Jenal, Urs |
Schirmer, Tilman, Professor |
Biozentrum, University of Basel |
01.04.2013 |
31.03.2016 |
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02/05/2024
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