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Aberrant mitochondrial activity: A common theme in the pathology of many diseases

Projectomschrijving

Verstoring van de energiehuishouding draagt bij aan het ziekteverloop in diabetes, kanker en hart- en vaatziekten. Met de XF analyzer van Seahorse Bioscience kunnen we deze verstoring meten in kleine hoeveelheden patiëntenmateriaal, waardoor onderzoeksresultaten sneller kunnen worden vertaald naar toepassing voor de patiënt.

Producten

Titel: Proteomic and biochemical studies of lysine malonylation suggests its malonic aciduria-associated regulatory role in mitochondrial function and fatty acid oxidation.
Auteur: Colak G, Pougovkina O, Dai L, Tan M, Te Brinke H, Huang H, Cheng Z, Park J, Wan X, Liu X, Yue WW, Wanders RJ, Locasale JW, Lombard DB, de Boer VC, Zhao Y
Titel: A computational study of the Warburg effect identifies metabolic targets inhibiting cancer migration
Auteur: Yizhak K, Le Dévédec SE, Rogkoti VM, Baenke F, de Boer VC, Frezza C, Schulze A, van de Water B, Ruppin E.
Titel: Mitochondrial NADP(H) deficiency due to a mutation in NADK2 causes dienoyl-CoA reductase deficiency with hyperlysinemia
Auteur: Houten SM, Denis S, Te Brinke H, Jongejan A, van Kampen AH, Bradley EJ, Baas F, Hennekam RC, Millington DS, Young SP, Frazier DM, Gucsavas-Calikoglu M, Wanders RJ.
Titel: Inhibiting epigenetic enzymes to improve atherogenic macrophage functions.
Auteur: Van den Bossche J, Neele AE, Hoeksema MA, de Heij F, Boshuizen MC, van der Velden S, de Boer VC, Reedquist KA, de Winther MP.
Titel: SIRT1/PGC1?-Dependent Increase in Oxidative Phosphorylation Supports Chemotherapy Resistance of Colon Cancer.
Auteur: Vellinga TT, Borovski T, de Boer VC, Fatrai S, van Schelven S, Trumpi K, Verheem A, Snoeren N, Emmink BL, Koster J, Rinkes IH, Kranenburg O.

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Samenvatting van de aanvraag

Mitochondria are the powerhouse of the cell and are as such essential for proper functioning of cells. Furthermore, mitochondrial activity directly influences a number of cellular functions ranging from cellular signaling to apoptosis. Aberrant mitochondrial function in patients with inherited metabolic diseases has long been recognized. More recently it has become increasingly clear that mitochondria also play a prominent role in the pathogenesis of many other diseases. Targeting cellular metabolism and mitochondrial activity in these diseases will provide novel therapeutic options. Tools that can quickly and non-invasively analyze cellular metabolism will greatly accelerate the path to achieve these goals. The XF extracellular flux analyzer from Seahorse Bioscience provides novel research opportunities and high-throughput analysis in living cells because of the use of optical biosensors in a microplate setup. The main advantages of the XF analyzer over traditional and alternative methods are that it uses a small number of cells (3x104 cells), it provides 500x higher throughput, it offers non-invasive and non-destructive measurements, it has 4 online injection ports and measures multiple analytes (O2, CO2, H+) simultaneously. Three investigators (Dr. Houten, Dr. Houtkooper and Dr. de Boer) in our research team have hands-on experience with the instrument from working abroad in labs that were the first users of the instrument. Now, we want to implement the instrument in our own research lines and make the instrument available to all researchers in the AMC and in The Netherlands. The instrument will be the cornerstone of the metabolic core facilities of laboratory Genetic Metabolic Diseases and the Amsterdam Center for Metabolism, which also offers high quality metabolomics and in vivo mouse metabolic phenotyping facilities. We will use the instrument in our studies for understanding the pathophysiological mechanisms of metabolic, inflammatory and cardiovascular diseases. Since this will be the first operational instrument in The Netherlands, investing in this instrument will further strengthen the leader position of the AMC in metabolic diseases both nationally and internationally. Furthermore, because mitochondrial dysfunction is a common underlying cause in diseases, the instrument will be used not only to study metabolic diseases but will benefit researchers in immunology, cancer and cardiovascular diseases as well. Synopsis: - The XF extracellular flux analyzer offers high-throughput studies in low numbers of intact cells and allows for fast clinical translation - The instrument will be implemented within existing infrastructure in our metabolic facility - The XF extracellular flux analyzer will be the cornerstone in the AMC core facilities for metabolic studies - Our labs have a long-standing internationally renowned metabolic expertise - We have extensive hands-on experience with the XF analyzers

Onderwerpen

Kenmerken

Projectnummer:
91112009
Looptijd: 100%
Looptijd: 100 %
2012
2018
Onderdeel van programma:
Gerelateerde subsidieronde:
Projectleider en penvoerder:
Prof. dr. R.J.A. Wanders
Verantwoordelijke organisatie:
Amsterdam UMC - locatie AMC