Thursday, April 6, 2017 - 12:00
Specific location: 
Room 343

BMC Seminar: Thursday, 6th April at 12:00, Room 343, Læknagarður

Speaker: Freyr Jóhannsson, PhD student.Center for Systems Biology, University of Iceland.

Title: A biochemically accurate model of platelet metabolism

Abstract: Platelets are a practical primary cell model system to study metabolism due to their supposed lack of genetic regulation. Platelets are stored in blood banks for use in various patient support treatements but their storage is limited on account of activation and risk of bacterial infections. Platelets are the smallest cellular constituents that circulate in the blood and are of vital importance for hemostasis.  The role of metabolism in platelet biology is not well understood. Here we investigated platelets collected from 64 donors over the time of one week in order to define basal platelet metabolism. We built a biochemical network of platelet metabolism and used it to investigate changes in metabolism during platelet storage.Metabolomics data from buffy coat (BC) platelet units were split into two metabolic phenotypes (metabotypes) representative of days 1-3 (Stage I) and days 4-6 (Stage II) of storage.Changes to metabolism were studied by comparing model predictions between the two stages. Platelet qualitycontrol markers, follow up 13C metabolic tracer and proteomic validation experiments were used to verify model predictions and refine the metabolic network model. Glycolysis, glutaminolysis and acetate oxidation were shown to be more active at later stages of storage while the activity of the citric acid cycle and oxidative phosphorylation decreased. Protein analysis suggest fewer and/or less functional mitochondria induce TCA cycle flux alterations. During storage platelets secrete signalling components that can have clinically adverse effects following transfusion. We are now closer to understanding how metabolism changes during storage and is associated with platelet payload secretion.

Þú ert að nota: