Dr. rer. nat. Michal Or-Guil

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• NW: Dynamische Mechanismen von B-Zell-Selektion und Charakterisierung von Proteinbindungseigenschaften: Theoretische und experimentelle Untersuchungen

  Quelle ↗

  Ziel der Forschungsgruppe ist es, ein genaueres Bild von den Mechanismen zu gewinnen, die die Zellen des adaptiven Immunsystems veranlassen, Antigene zu erkennen. Das Hauptaugenmerk gilt dabei einerseits den Mechanismen der B-Zell-Selektion, die anhand von Experimenten in Keimzentren und von mathematischen Modellen zu untersuchen sind, und andererseits der Bestimmung von Merkmalen der Gesamtheit der Antikörper, die mit Hilfe von Simulationen und Datenanalyse von Protein-Antikörper-Bindungen durchgeführt werden.

• Systems Biology Tools Development for Cell Therapy and Drug Development - SYSTHER

  Quelle ↗

  SYSTHER is a virtual institute consisting of partners from Germany and Slovenia. It was established to investigate and improve solid tumor treatment based on systems biology approaches. Identification of target genes and proteins, and subsequent mathematical modelling of candidate pathways, intracellular networks and interaction dynamics of immunocompetence, tumor and stem cells aim at elucidating mechanisms of tumor immunomodulation and the role of tumor stem cells in solid, non-metastasizing tumors, improving thus therapeutic strategies. Serum antibody profiling and gene expression analysis of tumor and stem cells shall further lead to the understanding of immunomodulation mechanisms.

• NW: Dynamical Mechanisms of B-Cell Selection and Charactarization of Protein Binding Properties: Theoretical and experimental investigations

  Quelle ↗

  Mammals possess immune systems to resist disease. In order to identify a foreign organism, such systems exploit the protein binding activity of antibodies. In dependence on the invader, highly specialized antibodies are secreted by suitable B-cells which are selected out of a large cell pool and induced to expand their population. The project aims at answering questions like: What are the mechanisms governing the selection of most suitable cells, and how are the selected cells improved during the course of an acute immune response? Furthermore, what recognition properties must a set of antibodies possess to be able to locate any invading pathogen? The project will pursue an interdisciplinary ansatz combining three subprojects in order to approach those questions. On the one hand, the dynamic behavior of B-cells in the tissues where selection occurs will be investigated experimentally and by means of computer simulations and data analysis. On the other hand, features of immune cell population dynamics shall be determined on the basis of mathematical models, utilizing the concept of an abstract space representing recognition capabilities of antibodies, the so called shape space. Finally, a shape space shall be designed from experimental data with the aim of characterizing and predicting protein binding properties.

• BKV, CMV, and EBV Interactions and their Effect on Graft Function One Year Post-Renal Transplantation: Results from a Large Multi-Centre Study

  2018

  EBioMedicine · DOI

  Background: BK virus (BKV), Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivations are common after kidney transplantation and associated with increased morbidity and mortality. Although CMV might be a risk factor for BKV and EBV, the effects of combined reactivations remain unknown. The purpose of this study is to ascertain the interaction and effects on graft function of these reactivations. Methods: 3715 serum samples from 540 kidney transplant recipients were analysed for viral load by qPCR. Measurements were performed throughout eight visits during the first post-transplantation year. Clinical characteristics, including graft function (GFR), were collected in parallel. Findings: BKV had the highest prevalence and viral loads. BKV or CMV viral loads over 10,000 copiesmL -1 led to significant GFR impairment. 57 patients had BKV-CMV combined reactivation, both reactivations were significantly associated (p = 0.005). Combined reactivation was associated with a significant GFR reduction one year post-transplantation of 11.7 mLmin -1 1.73 m -2 (p = 0.02) at relatively low thresholds (BKV > 1000 and CMV > 4000 copiesmL -1 ). For EBV, a significant association was found with CMV reactivation (p = 0.02), but no GFR reduction was found. Long cold ischaemia times were a further risk factor for high CMV load. Interpretation: BKV-CMV combined reactivation has a deep impact on renal function one year posttransplantation and therefore most likely on long-term allograft function, even at low viral loads. Frequent viral monitoring and subsequent interventions for low BKV and/or CMV viraemia levels and/or long cold ischaemia time are recommended.

• Quantifying the Length and Variance of the Eukaryotic Cell Cycle Phases by a Stochastic Model and Dual Nucleoside Pulse Labelling

  2014