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An apparatus for the real-time analysis of cellular metabolism

English title An apparatus for the real-time analysis of cellular metabolism
Applicant Freigang Stefan
Number 157702
Funding scheme R'EQUIP
Research institution Institut für Pathologie Universität Bern
Institution of higher education University of Berne - BE
Main discipline Immunology, Immunopathology
Start/End 01.12.2014 - 30.11.2015
Approved amount 120'433.00
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All Disciplines (2)

Discipline
Immunology, Immunopathology
Experimental Cancer Research

Keywords (8)

Cardiovascular disease; Leukemia; Inflammation; Inflammasome; Mucosal immunology; Bacterial pathogenesis; Metabolism; Cancer

Lay Summary (German)

Lead
Das metabolische System und das Immunsystem sind nicht nur essentiell, um unser internes Milieu gegen sich ständig ändernde Umwelteinflüsse konstant zu halten; beide Systeme sind auch auf mehreren Ebenen eng miteinander vernetzt und in ihrer Funktion voneinander abhängig. So ist das Immunsystem an der Regulierung von metabolischen Prozessen beteiligt, und spezifische metabolische Programme ermöglichen die Erhaltung und Funktionalität verschiedener Immunzellpopulationen. Gleichfalls trägt eine reziproke Interaktion zwischen metabolischer Dysfunktion und chronischer Entzündung zur Entstehung von metabolischen Erkrankungen, wie z.B. Adipositas und Herz-Kreislauferkrankungen, und von Krebserkrankungen bei.
Lay summary

Inhalt und Ziele des Projektes

Für das Verständnis des Einflusses metabolischer Programme auf die Zellfunktion in Homöostase, Entzündung oder maligner Transformation ist es essentiell, direkt Parameter des zellulären Metabolismus, wie z.B. die mitochondriale Atmung und die Glykolyse, mit der Charakterisierung von Zellfunktionen korrelieren zu können. Im vorliegenden Projekt soll die gegenseitige Interaktion zwischen Metabolismus und kardiovaskulärer Entzündung (Gruppe Freigang), maligner Transformation (Gruppe Tschan), und anti-mikrobieller Immunität (Gruppe Hapfelmeier) mithilfe des beantragten metabolischen Flux Analysegerätes untersucht werden. Der Apparat wird als Technologieplattform in der Abteilung für Experimentelle Pathologie installiert, und ist für alle Forschungsgruppen der Universität Bern zugänglich. Mehrere Arbeitsgruppen haben bereits starkes Interesse geäussert, diese Technologie für ihre Untersuchungen einzusetzen. Somit ist zu erwarten, dass der Apparat häufig genutzt wird, und die Grundlage für neue wissenschaftliche Zusammenarbeiten bildet.

Direct link to Lay Summary Last update: 03.12.2014

Responsible applicant and co-applicants

Publications

Publication
TNIK signaling imprints CD8+ T cell memory formation early after priming
Jaeger-Ruckstuhl Carla A., Hinterbrandner Magdalena, Höpner Sabine, Correnti Colin E., Lüthi Ursina, Friedli Olivier, Freigang Stefan, Al Sayed Mohamad F., Bührer Elias D., Amrein Michael A., Schürch Christian M., Radpour Ramin, Riether Carsten, Ochsenbein Adrian F. (2020), TNIK signaling imprints CD8+ T cell memory formation early after priming, in Nature Communications, 11(1), 1632-1632.
The regulation of inflammation by oxidized phospholipids.
Freigang Stefan (2016), The regulation of inflammation by oxidized phospholipids., in European Journal of Immunology, 46(8), 1818-1825.
TREM-1 links dyslipidemia to inflammation and lipid deposition in atherosclerosis
Zysset Daniel, Weber Benjamin, Rihs Silvia, Brasseit Jennifer, Freigang Stefan, Riether Carsten, Banz Yara, Cerwenka Adelheid, Simillion Cedric, Marques-Vidal Pedro, Ochsenbein Adrian F, Saurer Leslie, Mueller Christoph (2016), TREM-1 links dyslipidemia to inflammation and lipid deposition in atherosclerosis, in Nature Communications, 7, 13151.
Phospholipid oxidation generates potent anti-inflammatory lipid mediators that mimic structurally related pro-resolving eicosanoids by activating Nrf2.
Bretscher Peter, Egger Julian, Shamshiev Abdijapar, Trötzmüller Martin, Köfeler Harald, Carreira Erick, Kopf Manfred, Freigang Stefan (2015), Phospholipid oxidation generates potent anti-inflammatory lipid mediators that mimic structurally related pro-resolving eicosanoids by activating Nrf2., in EMBO Molecular Medicine, 7(5), 593-607.
T cell lipid peroxidation induces ferroptosis and prevents immunity to infection.
Matsushita Mai, Freigang Stefan, Schneider Christoph, Conrad Marcus, Bornkamm Georg, Kopf Manfred (2015), T cell lipid peroxidation induces ferroptosis and prevents immunity to infection., in Journal of Experimental Medicine, 212(4), 555-568.
Total Synthesis of Prostaglandin 15d-PGJ(2) and Investigation of its Effect on the Secretion of IL-6 and IL-12.
Egger Julian, Fischer Stefan, Bretscher Peter, Freigang Stefan, Kopf Manfred, Carreira Erick (2015), Total Synthesis of Prostaglandin 15d-PGJ(2) and Investigation of its Effect on the Secretion of IL-6 and IL-12., in Organic Letters, 17(17), 4340-4343.
Discovery of a highly potent anti-inflammatory epoxyisoprostane-derived lactone.
Egger Julian, Bretscher Peter, Freigang Stefan, Kopf Manfred, Carreira Eric (2014), Discovery of a highly potent anti-inflammatory epoxyisoprostane-derived lactone., in J Am Chem Soc, 136(50), 17382-17385.

Collaboration

Group / person Country
Types of collaboration
Prof. Dr. Shida Yousefi Switzerland (Europe)
- Research Infrastructure
Prof. Dr. Hans-Uwe Simon Switzerland (Europe)
- Research Infrastructure
Prof. Dr. Thomas Kaufmann Switzerland (Europe)
- Research Infrastructure
PD Dr. Siamak Djafarzadeh Switzerland (Europe)
- Research Infrastructure
Prof. Dr. Stephan Jakob Switzerland (Europe)
- Research Infrastructure

Awards

Title Year
Pfizer Research Prize 2015 2015
Research Prize of the Swiss Heart Foundation 2015

Associated projects

Number Title Start Funding scheme
143739 PU.1-regulated apoptosis and autophagy pathways in neutrophil differentiation of normal and leukemic myeloid precursor cells 01.01.2013 Project funding (Div. I-III)
152872 Molecular mechanisms of lipid-induced vascular inflammation in atherosclerosis 01.01.2015 Project funding (Div. I-III)
138452 Pathogen and commensal immunity compared in a reversible infection model that uncouples immunity from pathogen immune evasion 01.09.2012 Project funding (Div. I-III)

Abstract

It is increasingly recognized that the metabolic system and the immune system are not only essential for maintaining and defending a constant internal milieu against environmental challenges, but also that they are directly linked at multiple levels and critically depend on each other’s function. For example, innate and adaptive immune mechanisms regulate metabolic homeostasis, whereas distinct metabolic programs guarantee the maintenance and effector functions of different immune cell subsets. Furthermore, metabolic dysfunction and chronic inflammation reciprocally interact in the pathogenesis of metabolic disorders, including obesity, diabetes or cardio-vascular disease, and of cancer. To understand the role of cellular metabolic programs in the determination of cell fate and function during homeostasis, inflammation or malignant transformation it is thus essential to directly correlate parameters of cellular metabolism, such as mitochondrial respiration and glycolysis, with the characterization of cellular function in vitro and in vivo. Here, we apply for subsidiary funding for the purchase of an Extracellular Flux Analyzer in combination with a hypoxia chamber in order to obtain this key technology for our research. In particular, we aim to investigate the mutual crosstalk between metabolism and vascular inflammation (Group Freigang), malignant transformation (Group Tschan) and anti-microbial immunity (Group Hapfelmeier). The apparatus will be established as a technology platform in the Division of Experimental Pathology and will be made accessible to the scientific community at the University of Bern. Given that several groups working in the fields of immunology, experimental medicine and cell biology have already expressed their strong interest in applying this technology to their own research, we anticipate that the apparatus will be frequently used and will foster scientific collaborations in the future.
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