Project

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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

Responsible applicant and co-applicants

Employees

Publications

Publication
Mitigation of Pseudomonas syringae virulence by signal inactivation
Sieber Simon, Mathew Anugraha, Jenul Christian, Kohler Tobias, Bär Max, Carrión Víctor J., Cazorla Francisco M., Stalder Urs, Hsieh Ya-Chu, Bigler Laurent, Eberl Leo, Gademann Karl (2021), Mitigation of Pseudomonas syringae virulence by signal inactivation, in Science Advances, 7(37), eabg2293.
Syntheses and biological investigations of kirkamide and oseltamivir hybrid derivatives
Sieber Simon, Hsiao Chien-Chi, Emmanouilidou Despina, Debowski Aleksandra W., Stubbs Keith A., Gademann Karl (2020), Syntheses and biological investigations of kirkamide and oseltamivir hybrid derivatives, in Tetrahedron, 76(51), 131386-131386.
Biosynthesis and Structure–Activity Relationship Investigations of the Diazeniumdiolate Antifungal Agent Fragin
Sieber Simon, Daeppen Christophe, Jenul Christian, Mannancherril Vidya, Eberl Leo, Gademann Karl (2020), Biosynthesis and Structure–Activity Relationship Investigations of the Diazeniumdiolate Antifungal Agent Fragin, in ChemBioChem, 21(11), 1587-1592.
Microviridin 1777: A Toxic Chymotrypsin Inhibitor Discovered by a Metabologenomic Approach
Sieber Simon, Grendelmeier Simone M., Harris Lonnie A., Mitchell Douglas A., Gademann Karl (2020), Microviridin 1777: A Toxic Chymotrypsin Inhibitor Discovered by a Metabologenomic Approach, in Journal of Natural Products, 83(2), 438-446.

Datasets

Microcystis aeruginosa EAWAG127a, whole genome shotgun sequencing project.

Author Sieber, Simon; Grendelmeier, Simone M.; Harris, Lonnie A.; Mitchell, Doug A.; Gademann, Karl
Publication date 28.01.2020
Persistent Identifier (PID) https://www.ncbi.nlm.nih.gov/nuccore/NZ_SRLN00000000.1
Repository NCBI/GenBank
Abstract
LOCUS NZ_SRLN01000000 4967080 bp DNA linear BCT 29-OCT-2020DEFINITION Microcystis aeruginosa EAWAG127a, whole genome shotgun sequencing project.ACCESSION NZ_SRLN00000000VERSION NZ_SRLN00000000.1DBLINK BioProject: PRJNA224116 BioSample: SAMN10998537 Assembly: GCF_008757435.1KEYWORDS WGS; RefSeq.SOURCE Microcystis aeruginosa EAWAG127a ORGANISM Microcystis aeruginosa EAWAG127a Bacteria; Cyanobacteria; Oscillatoriophycideae; Chroococcales; Microcystaceae; Microcystis.REFERENCE 1 (bases 1 to 4967080) AUTHORS Sieber,S., Grendelmeier,S.M., Harris,L.A., Mitchell,D.A. and Gademann,K. TITLE Microviridin 1777: A Toxic Chymotrypsin Inhibitor Discovered by a Metabologenomic Approach JOURNAL J Nat Prod 83 (2), 438-446 (2020) PUBMED 31989826REFERENCE 2 (bases 1 to 4967080) AUTHORS Grendelmeier,S.M., Sieber,S. and Gademann,K. TITLE Direct Submission JOURNAL Submitted (03-APR-2019) Chemistry, University of Zurich, Winterthurerstrasse 190, Zurich 8050, SwitzerlandCOMMENT REFSEQ INFORMATION: The reference sequence is identical to SRLN00000000.1. The Microcystis aeruginosa EAWAG127a whole genome shotgun (WGS) project has the project accession NZ_SRLN00000000. This version of the project (01) has the accession number NZ_SRLN01000000, and consists of sequences SRLN01000001-SRLN01000022. Bacteria and source DNA available from Cyanobacteria Collection at University of Zurich. Annotation was added by the NCBI Prokaryotic Genome Annotation Pipeline (released 2013). Information about the Pipeline can be found here: https://www.ncbi.nlm.nih.gov/genome/annotation_prok/ ##Genome-Assembly-Data-START## Assembly Date :: JUL-2018 Assembly Method :: HGAP v. 2.3.0 Genome Representation :: Full Expected Final Version :: Yes Genome Coverage :: 63.0x Sequencing Technology :: PacBio RSII ##Genome-Assembly-Data-END## ##Genome-Annotation-Data-START## Annotation Provider :: NCBI RefSeq Annotation Date :: 10/29/2020 04:20:22 Annotation Pipeline :: NCBI Prokaryotic Genome Annotation Pipeline (PGAP) Annotation Method :: Best-placed reference protein set; GeneMarkS-2+ Annotation Software revision :: 4.13 Features Annotated :: Gene; CDS; rRNA; tRNA; ncRNA; repeat_region Genes (total) :: 4,779 CDSs (total) :: 4,722 Genes (coding) :: 4,214 CDSs (with protein) :: 4,214 Genes (RNA) :: 57 rRNAs :: 2, 2, 2 (5S, 16S, 23S) complete rRNAs :: 2, 2, 2 (5S, 16S, 23S) tRNAs :: 46 ncRNAs :: 5 Pseudo Genes (total) :: 508 CDSs (without protein) :: 508 Pseudo Genes (ambiguous residues) :: 0 of 508 Pseudo Genes (frameshifted) :: 227 of 508 Pseudo Genes (incomplete) :: 250 of 508 Pseudo Genes (internal stop) :: 146 of 508 Pseudo Genes (multiple problems) :: 105 of 508 CRISPR Arrays :: 6 ##Genome-Annotation-Data-END##FEATURES Location/Qualifiers source 1..4967080 /organism="Microcystis aeruginosa EAWAG127a" /mol_type="genomic DNA" /strain="EAWAG127a" /isolation_source="Mazurian Lakes" /db_xref="taxon:2529855" /country="Poland" /collection_date="1965" /collected_by="Alfons Zehnder"WGS SRLN01000001-SRLN01000022WGS_SCAFLD NZ_SRLN01000001-NZ_SRLN01000022

Collaboration

Group / person Country
Types of collaboration
Katherine Ryan Canada (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Francisco Cazorla, University of Malaga Spain (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
XXVIII Congreso Nacional de Microbiología de la SEM Talk given at a conference An update on bacterial quorum sensing: new molecules, new mechanisms 28.06.2021 Madrid, Spain Gademann Karl; Mathew Anugraha; Paganini Leonardo; Eberl Leo;
Departmental Seminar, Suzhou, China Individual talk Discoveries and Surprises with Natural Products 31.10.2020 Suzhou, China Gademann Karl;
China Pharmaceutical University Nanjing Individual talk Reduce to the Max: Investigating Biological Processes with Truncated Natural Products 29.10.2019 Nanjing, China Gademann Karl;


Awards

Title Year
Fellow of Chemistry Europe 2020

Associated projects

Number Title Start Funding scheme
192800 The role of vesicle formation in biofilm development 01.06.2020 Project funding

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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