Research

Antibody-mediated immune reactions to endogenous proteins

Mechanobiology of iPSC-derived cardiomyocytes

Immunogenicity of nanoparticles

1. Antibody-mediated immune reactions to endogenous proteins

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Immunogenicity (i.e. the ability of a particular substance to provoke an immune response in humans or animals) represents a major challenge for the development of new biotherapeutics. It is essential to identify those factors which induce an immune response which sometimes may lead to autoimmune diseases.

We combine biophysical techniques (e.g. circular dichroism spectroscopy, single molecule force spectroscopy, calorimetry, fluorescence microscopy) and molecular dynamic simulation studies to predict whether mutations, posttranslational modifications or stress conditions (e.g. pH, drugs) may induce protein immunogenicity.

Of particular interest is the conformational dynamics of proteins involved in autoimmune diseases (e.g. soluble beta2-glycoprotein I and transmembrane. integrin alpha2b beta3 integrin. We also study the interaction of proteins with autoantibodies and with cells of the immune system.

Funded research projects: European Research Council (ERC) Starting Grant (PredicTOOL grant number 637877),European Union (PePPP grant number ESF/14-BM-A55-0047/16).

2. Mechanobiology of iPSC-derived cardiomyocytes

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Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) possess outstanding capacity for cardiac regeneration and represent models of cardiac diseases. We investigate using 3D engineered surfaces with various properties (e.g. size, shape, elasticity) the mechanobiology of iPSC-CM under physiological and pharmacological conditions. The main objective is to understand the mechanisms through which the complex physico-chemical interactions between cardiomyocytes and their environment are translated into biochemical and cellular responses with the final purpose to understand the basic functionality of cardiac cells and to fabricate in vitro myocardial tissue constructs.

Funded research project: German Centre for Cardiovascular Research (DZHK, grant number 81X2400128).

3. Immunogenicity of nanoparticles

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Nanoparticles can stimulate and/or suppress the immune response by binding to blood proteins. Although the compatibility of the nanoparticles with the immune system is largely determined by their physico-chemical properties (e.g. size, shape, charge, surface groups), the effect of nanoparticle properties on the immune system is little explored. Using in vitro tools we predict and control the immunogenicity of nanoparticles by adjusting their physical properties (e.g. size, surface charge) and targeting ligands (e.g. antibodies, proteins). 

We functionalize gold- or magnetic nanoparticles with biopolymers and investigate protein corona formation using blood proteins (e.g. transferrin, human serum albumin) and the immunogenicity of the bioconjugates.

Funded research project: German Ministry of Education and Research (BMBF, grant number: FKZ:03Z22C51).

Collaborators
  • Prof. Ali Abou-Hassan (Sorbonne University, Paris, France)
  • Prof. Adnane Achour (Karolinska Institute, Stockholm, Sweden)
  • Dr. Lukas Cyganek (University Medicine Göttingen, Germany)
  • Dr. Susan Köppen (Hybrid Materials Interfaces, University of Bremen, Germany)
  • Prof. Markus Lerch (University Medicine Greifswald, Germany)
  • Prof. Luis M. Liz-Marzán (CICbiomaGUNE, San Sebastian, Spain)
  • Prof. Markus Münzenberg (University of Greifswald, Germany)
  • Prof. Anisur Rahman (Department of Rheumatology, University College London, United Kingdom)
  • Prof. Karen Vanhoorelbeke (Laboratory for Thrombosis Research, KU Leuven, Belgium)

aktualisiert am 20.09.2019 durch
N. Geist