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A New Class of Signal Molecules in Bacteria: Data-Driven Discovery, Mechanism, and Biological Function (Signalin’Bac)

Applicant Gademann Karl
Number 186410
Funding scheme Sinergia
Research institution Institut für Chemie Universität Zürich
Institution of higher education University of Zurich - ZH
Main discipline Interdisciplinary
Start/End 01.10.2019 - 30.09.2023
Approved amount 1'868'605.00
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All Disciplines (3)

Discipline
Interdisciplinary
Experimental Microbiology
Organic Chemistry

Keywords (4)

Organic Chemistry; Microbiology; Burkholderia; Natural Products

Lay Summary (German)

Lead
Bakterien kommunizieren durch chemische Signale miteinander - dieses Projekt untersucht wie.
Lay summary
Bakterien kommunizieren durch chemische Signale miteinander und können so auf die Umgebung reagieren. Dies hat Konsequenzen zum Beispiel auch für Krankheiten, da Virulenz oft durch solche Mechanismen gesteuert wird. Dieses Projekt untersucht eine neue Klasse von Signalmolekülen, die sogenannten Diazeniumdialote.  Wie wenn man eine neue Sprache entdecken und beschreiben würde, geht es auch hier darum, neue Moleküle zu beschreiben, ihre Funktion zu verstehen, wie sie gebildet werden, und welchen Zusammenhang sie in biologischen Systemen zeigen. Dies kann einerseits für unser Verständnis des sozialen Verhaltens von Bakterien zentral sein, aber auch neue Methoden und Verfahren ermöglichen, um Virulenz und Pathogenität zu verhindern.
Direct link to Lay Summary Last update: 29.08.2019

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Employees

Abstract

Bacteria use chemical compounds for cell-cell communication. This process is of relevance for various biological processes such as virulence, biofilm formation, or luminescence, with ramifications to different fields such as human health, crop protection, and industrial biotechnology. Although a number of communication systems have been established and characterized over the last years, their number has remained surprisingly low. In collaboration of the Eberl and Gademann groups, we have identified this year a new class of signal molecules containing a diazenium diolate group.The ultimate goal of this proposal is to provide a detailed understanding of this new class of signaling molecules in bacteria, with regard to their biosynthesis, their biological function, their mechanism of action and their role in pathogenesis. Specifically, we aim to investigate (1) the structure, distribution, and biological activities of diazenium diolate-based signal molecules, (2) the signal perception, downstream regulatory cascades, and the associated bacterial phenotypes, (3) their role of in metal homeostasis, and (4) the biosynthesis of these signal molecules.Akin to discovering a new language, this work will therefore unravel the complex molecular structures of a novel class of bacterial signals, their intricate mechanism of action, and their importance in the regulation of different phenotypic traits. Preliminary data suggest that this class of signaling molecules might be involved in society-relevant problems: From pathogenicity in plants and animals to beneficial biocontrol functions. Over the last ten years, the Eberl and Gademann research groups have established a close research collaboration that successfully investigated a number of scientific problems related to bacterial signaling or bacteria/plant symbiosis. The proposed research builds on this strong collaboration between two research groups in chemistry and microbiology, with a documented record of excellence as judged by outstanding joint publications, awards to PIs and students alike, and published comments by peers.We will pursue an interdisciplinary approach in which projects are thoroughly investigated by scientists with complementary expertise, graduate students will have joint PhD committees, and secondments in different labs will strengthen the transdisciplinary knowledge of the researchers. Joint teaching efforts on the master level will educate the next generation of students, and two international symposia will allow for dissemination of the science and fostering the community. Overall, this project leverages the complementary expertise of two leading groups in chemistry and biology with documented excellence in interdisciplinary research. The next generation of scientists will work jointly on all projects and will be educated to tackle the transdisciplinary challenges of the next decades. The strong consortium will investigate a novel chemical language in bacteria, which has the potential to impact science and society.
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