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Deciphering Complex Signaling in Disease Using a Next-Generation High-Resolution LC-MS Platform

English title Deciphering Complex Signaling in Disease Using a Next-Generation High-Resolution LC-MS Platform
Applicant Wymann Matthias
Number 198526
Funding scheme R'EQUIP
Research institution Departement Biomedizin Universität Basel
Institution of higher education University of Basel - BS
Main discipline Experimental Cancer Research
Start/End 01.05.2021 - 30.04.2022
Approved amount 638'000.00
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All Disciplines (5)

Discipline
Experimental Cancer Research
Biochemistry
Embryology, Developmental Biology
Cellular Biology, Cytology
Genetics

Keywords (10)

quantitative cellular signaling; cancer; mass spectrometry; neuromuscular disorders; biomedical research; high resolution proteomics; chemical biology; skeletal muscle; development; immunology

Lay Summary (German)

Lead
Die Analyse von zellulären Proteinen an der Universität Basel soll durch die Anschaffung eines Massenspektrometers der neusten Generation verbessert werden. Eine erhöhte Empfindlichkeit und neue Fragmentierungs-Techniken werden es ermöglichen, neuartige Methoden zur Untersuchung von Proben aus Grundlagenforschung und Klinik zu etablieren.
Lay summary

In den letzten Jahrzehnten haben sich Techniken zur Analyse von DNA und RNA rasant entwickelt. Mutationsanalysen und Genexpressions-Studien können deshalb heutzutage schnell umgesetzt werden. Die Analyse der anschliessend exprimierten Proteine und ihrer Modifikationen hat sich allerdings nicht in gleichem Masse weiterentwickelt. Die Anzahl Proben, die verarbeitet werden können, die benötige Menge an Protein für eine Analyse, und die Auflösung vieler Massenspektrometer limitierten in der Vergangenheit die Möglichkeiten und Anwendungsgebiete von sogenannten LC/MS Methoden [eine Verbindung von Liquid-Chromatographie (LC) und Massenspektrometrie (MS)]. Eine neue Gerätegeneration verbessert nun aber Durchsatz und Empfindlichkeit von Proteinanalysen mittels LC/MS.

Das Departement für Biomedizin der Universität Basel will deshalb ein Massenspektrometer der neusten Generation anschaffen, um in einer mit dem Biozentrum gemeinsam betriebenen «Proteomics Core Facility (PCF)» eine 10-fach erhöhte Sensitivität und einen gesteigerten Durchsatz zu erreichen. Zusätzlich soll das Gerät mit einem «Ultraviolet Photodissociation (UVPD)» Modul ausgerüstet werden, welches neue Protein Fragmentierungsmethoden ermöglicht. Im akademischen Umfeld der Schweiz wäre das damit ein einzigartiges Gerät, welches das Verständnis biologischer und pathologischer Prozesse, wie sie in der Region Basel untersucht werden, bedeutend vorantreiben wird.

Direct link to Lay Summary Last update: 17.11.2020

Responsible applicant and co-applicants

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182388 Drosha and its RNA binding partners in neurogenesis 01.01.2019 Project funding
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Abstract

Over the last decades, there has been an explosion in high throughput and increasingly sensitive genomics technologies, allowing RNA analysis of gene expression in thousands of samples down to the single cell level. This has revolutionized our understanding of biological processes, development, and disease etiology including cancer. However, proteomic analysis of gene expression and protein modifications has not seen this level of development. The speed and sensitivity of most mass spectrometry (MS) techniques limits utilization of proteomics in projects, particularly when sample size is limited, protein levels are low and reproducible, cross-sample quantitation is required. This is particularly important for analysis of large protein complexes and post-translational modifications. The current state of the art, next generation Orbitrap Tribrid Eclipse equipped with an Ultraviolet Photodissociation (UVPD) unit that we request support to purchase, has more than 10-times higher sensitivity and is significantly faster than current LC-MS devices.The UVPD unit enables unique proteomic analyses that are currently not available in the academic environment in Switzerland. This will increase throughput of sampling and precision of the data to unprecedented levels, opening up new avenues for basic and clinical research as well as the analysis of limited patient samples.Through its integration into the Proteomics Core Facility (PCF) at the University of Basel, the requested Orbitrap Tribrid Eclipse with UVPD will be accessible to regional researchers at the Department of Biomedicine (DBM), Biozentrum, and other University of Basel departments, including the D-BSSE, FMI, and the University of Applied Sciences (FHNW). The sensitivity and speed of this novel device will circumvent the bottleneck currently limiting proteomics research at the DBM. The DBM has committed to establishing the Orbitrap Tribrid Eclipse with UVPD by providing a 100% proteomics expert that will be integrated into the PCF. The pipelines for data analysis and cross-department and institutional bioinformatic analysis of the data are already in place. This will ensure the seamless operation, development and analysis of the output data. The insights gained through the Orbitrap Tribrid Eclipse with UVPD will be critical for a better understanding of dynamic biological processes, and will spur the design of innovative therapeutic approaches to counteract resistance mechanisms in human disease.
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