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Advancing Quantitative and Post-Translational Modification Proteomics by Latest Generation Mass Spectrometry

English title Advancing Quantitative and Post-Translational Modification Proteomics by Latest Generation Mass Spectrometry
Applicant Schlapbach Ralph
Number 145021
Funding scheme R'EQUIP
Research institution Functional Genomics Center Zürich ETH Universität Zürich
Institution of higher education ETH Zurich - ETHZ
Main discipline Biochemistry
Start/End 01.07.2013 - 30.06.2014
Approved amount 734'810.00
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All Disciplines (16)

Discipline
Biochemistry
Botany
Pathophysiology
Experimental Cancer Research
Cellular Biology, Cytology
Neurophysiology and Brain Research
Environmental Research
Zoology
Endocrinology
Immunology, Immunopathology
Medical Microbiology
Experimental Microbiology
Pharmacology, Pharmacy
Physiology : other topics
Cardiovascular Research
Molecular Biology

Keywords (5)

proteomics; bioinformatics; liver regeneration; plant metabolism; wound healing

Lay Summary (German)

Lead
Fortschritte in der quantitativen Analyse von biologischen Systemen auf system-weiter Ebene (Omics) sind direct abhängig von den technischen Möglichkeiten und der Weiterentwicklung von analytischen Systemen. Dies trifft in speziell hohem Masse auf das Arbeitsgebiet der Proteomics zu, der umfassenden Identifikation und Quantifizierung von Proteinen und deren Modifikationen in komplexen biologischen Systemen und Organismen.
Lay summary

Inhalt und Ziel des Forschungsprojekts

 Das Projekt hat zum Ziel, durch die Implementierung neuester Massenspektrometrie-Technologie und der Entwicklung und Verbesserung von neuen und bestehenden Methoden, unterschiedlichste Forschungsarbeiten unter Anwendung von Proteomics-Ansätzen voranzutreiben.

Die Forschungsprojekte I (Tracking plant proteins) and II (Regulatory network of starch metabolism) zielen darauf ab, die Kontrollmechanismen und regulierenden Komponenten von dynamischen Stoffwechselprozessen in Pflanzen auf Proteom-weiter Ebene zu analysieren. Projekt III (Liver regeneration) nutzt isotope-markierte Verbindungen und deren nachfolgende massenspektrometrische Analyse zur Kennzeichnung und Quantifizierung von Proteinen in hochkomplexen biologischen Proben. Projekt IV (Wound healing) wendet ein innovatives analytisches Konzept (middle-down proteomics) zur Aufklärung der entsprechenden biologischen Prozesse an.

Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojekts

Die moderne biologische Forschung in den verschiedensten Bereichen, illustriert durch die hier unterstützten Forschungsprojekte, welche von der grundlegenden Pflanzenbiologie bis zu Wundheilungs- und Regenerationsprozessen bei Säugetieren reichen, wird stark von den vorhandenen technischen Möglichkeiten beeinflusst und profitiert in erheblichem Masse von neuen Methoden und Technologien. Durch die Verknüpfung von technologischem, methodischem und biologischem Know-How, wird die Forschung effizienter und erzielt Fortschritte in kürzerer Zeit und in umfassenderem Masse.

 

Direct link to Lay Summary Last update: 12.11.2012

Responsible applicant and co-applicants

Publications

Publication
Matrix metalloproteinase 10 degradomics in keratinocytes and epidermal tissue identifies bioactive substrates with pleiotropic functions
Schlage P. Kockmann T. Sabino F. Kizhakkedathu J. N. & auf dem Keller U. (2015), Matrix metalloproteinase 10 degradomics in keratinocytes and epidermal tissue identifies bioactive substrates with pleiotropic functions, in Mol. Cell Proteomics, 14(12), 3234-3246.
Monitoring matrix metalloproteinase activity at the epidermal-dermal interface by SILAC-iTRAQ-TAILS
Schlage P. Kockmann T. Kizhakkedathu J. N. & auf dem Keller U (2015), Monitoring matrix metalloproteinase activity at the epidermal-dermal interface by SILAC-iTRAQ-TAILS, in Proteomics, 15(14), 2491-2502.
Proteasome targeting of proteins in Arabidopsis leaf mesophyll, epidermal and vascular tissues
Svozil J Gruissem W Baerenfaller K (2015), Proteasome targeting of proteins in Arabidopsis leaf mesophyll, epidermal and vascular tissues, in Front Plant Sci, 6(376), 1-17.
Comprehensive proteomic analysis of 3D human liver and cardiac spheroids for drug toxicity investigation
N.Selevsek J.Grossmann P.Nanni C.Fortes P.Gunness J.Kelm R.Schlapbach (2014), Comprehensive proteomic analysis of 3D human liver and cardiac spheroids for drug toxicity investigation, in Proceedings IMSC 2014 , IMSC, Geneva.

Collaboration

Group / person Country
Types of collaboration
Platform Collaborations Local Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
- Exchange of personnel
Collaboration of the Research Project PIs Netherlands (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Platform Collaborations International Netherlands (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Platform Collaborations National Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
3D Cell Culture 2016: How close to 'in vivo' can we get? Models, applications & translation Talk given at a conference Comprehensive molecular profiling of organoids and patient tissue in the context of toxicogenomics 19.04.2016 Freiburg, Germany Schlapbach Ralph;
Post-doc-day Poster Proteomic analysis of microtissues 21.05.2015 Wädenswil, Switzerland Schlapbach Ralph;
HUPO 2014 Talk given at a conference Comprehensive proteomic analysis of 3D human liver spheroids for drug toxicity investigation 05.10.2014 Madrid, Spain Schlapbach Ralph;
D-BIOL Meeting 2014 Talk given at a conference Proteomics methods and applications 11.06.2014 Davos, Switzerland Schlapbach Ralph;
HeCaToS Meeting Talk given at a conference Comprehensive proteomic analysis of 3D human liver spheroids 08.05.2014 London, Great Britain and Northern Ireland Schlapbach Ralph;


Self-organised

Title Date Place
Mass spectrometry training and application workshop 04.11.2013 Zurich, Switzerland

Knowledge transfer events



Self-organised

Title Date Place
Omics technologies for life science research 02.02.2016 Zurich, Switzerland

Communication with the public

Communication Title Media Place Year
Media relations: print media, online media Wide range of technological support for omics research X-Letter Italian-speaking Switzerland German-speaking Switzerland Rhaeto-Romanic Switzerland International Western Switzerland 2016

Associated projects

Number Title Start Funding scheme
138500 Haptoglobin and the macrophage scavenger receptor CD163 - redirecting hemoglobin toxicity towards protection 01.01.2012 Project funding
132971 Function of Arabidopsis RBR in stem cell differentiation and developmental transition 01.10.2010 Project funding
173668 SCI-NET - Identification of novel bioactive mediators of tissue scarring, inflammation and extracellular matrix remodeling after spinal cord injury 01.11.2017 ERA-NET NEURON
164099 Improved performance and reliability of high throughput metabolomics by ion mobility - time of flight mass spectrometry 01.01.2016 R'EQUIP
158542 PSC Discovery Program for Youth 01.04.2015 Agora
131074 Discovering the roles of debranching enzymes in starch metabolism in arabidopsis 01.04.2010 Project funding
132884 Fibroblast growth factor signaling in skin barrier function, wound repair and inflammatory skin disease 01.10.2010 Project funding
133123 Interplay between mismatch repair and other pathways of DNA metabolism 01.10.2010 Project funding

Abstract

The investigation of protein identities, abundances, modifications, interactions, and the unnumbered biologically functional and structural systems and networks at comprehensive scale are the ambitious goals of proteomics. Protein analysis was always an essential component of biological research but the technologies available for the investigation of the mentioned aspects in the protein space were limiting the scope and scale of the respective analyses and the resulting data. While the continued development of analytical technologies and methods has led to improvements in various fields of applying mass spectrometers to analytical challenges including biology and biomedicine, the recent years have seen a truly disruptive technology development that made possible the analysis and characterization of large numbers of proteins at formerly unknown high sensitivity, specificity, and speed. The Functional Genomics Center of ETH Zurich and University of Zurich has started to develop and implement proteomics technologies and methods for the support of the life science research community in 2002. Since then, a large number of research groups representing all major areas of biological and biomedical research has benefited from the proteomics infrastructure and know-how that is made available through the center's User Lab structure, allowing researchers to directly access high-end instrumentation and workflows after thorough training and with continuous support.The requested equipment ensures the continuation of this support at the highest possible performance level and even allows to further advance proteomics by exploiting a number of technical features that have become available only with a unique combination of the requested technology components: The Orbitrap Elite mass spectrometer of Thermo Fisher Scientific, with its mass resolution of 240’000 FWHM and data acquisition rates of 4Hz, in combination with a NanoMate ESI-Chip system, featuring exceptionally high ionization efficiency and the virtual absence of (post column) cross contaminations, enable uncompromised mass spectrometry and fraction collection at the same time. This combination opens up new possibilities in the analysis of proteins and their modifications at the protein (top-down) or large peptide (middle-down) level and will be instrumental to take the supported projects to the next level of sensitivity and accuracy of data generation. The representative research projects, led by the co-applicants of the proposal, illustrate the broad applicability and profound impact the technology will have on their research and emphasize the need for improved technologies including the further development of current approaches to advance not only analytically but also scientifically. In both described broader areas, the investigation of complex regulatory networks and processes in plants and the research on the components and processes in wound healing and tissue regeneration, existing state-of-the-art methods will be equally well supported by the requested equipment as will be the implementation of alternative and potentially even more powerful approaches.
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