Research on B cells and Allogeneic Immune Reactions

For the fourth time BIOSS is awarding the Barbara Hobom prize to two female Doctoral candidates.

Kathrin Kläsener (AG Reth) and Natalie Stickel (AG Zeiser) were selected to receive the Barbara Hobom Prize 2014. This distinction is awarded each year by the Cluster of Excellence BIOSS Centre for Biological Signalling Studies of the University of Freiburg for research projects in synthetic biology, signaling, and bioengineering. The purpose of the prize, which is worth a total of 10,000 euros, is to promote young female scientists. It was awarded to the 2 winners by Dr. Barbara Hobom, a group leader at the University Freiburg and later a successful science journalist. In an article published in 1979 she was one of the first to coin the term “synthetic biology”.

Kathrin Kläsener

Kathrin Kläsener is a PhD student in the Department of Molecular Immunology (Prof. Dr. Michael Reth) at the Institute for Biology III of the University Freiburg. In her PhD project she studies the nanoscale organization of antigen receptors on the cell membrane of B lymphocytes that are part of our humoral immune system. Signals from the antigen receptors control the activation and expansion of B cells. With the Fab based „proximity ligation assay“ (Fab-PLA) Mrs. Kläsener developed a technique that allows, for the first time, to monitor the conformation of antigen receptors at 10-20 nm distances. With this technique she could demonstrate that, on resting B cells, antigen receptors are multimers that only upon the binding to an antigen are opened. Interestingly, she also found that this receptor opening requires not only the binding to an antigen but also the intracellular tyrosine phosphatase kinase Syk. Through this "inside-out" signaling mechanism of Syk, the signal from the antigen receptor is amplified so that a B cell requires only a small amount of antigen to become fully active. In addition Mrs Kläseners work showed that not only antigen receptors, but also many other receptors such as B cell co-receptors are residing inside nanoscale membrane domains, also called protein islands, that are altered during B cell activation. Her results were published in the new open-access journal "eLife". In collaboration with several groups at the University Hospital Freiburg she currently is using the PLA technique for a better diagnostics of human diseases and a detailed study of human B cells

Natalie Stickel

Natalie Stickel is working on her doctoral dissertation under Prof. Dr. Robert Zeiser and is receiving a scholarship from the Spemann Graduate School of Biology and Medicine (SGBM). The main goal of her research is to explain the molecular mechanisms that can lead to an outbreak of an undesirable and dangerous reaction of the immune system, the so-called acute graft-versus-host disease (GvHD), following an allogeneic blood stem cell transplantation (allo-HSCT). Activated T-cells of the donor assume a key role in GvHD in that they identify the epithelial cells of the host as foreign and damage them. In studies on the internal regulatory mechanisms of the donor T-cells, Stickel succeeded in demonstrating that a short non-coding RNA molecule, miR-146a, inhibits an important signaling axis in these cells and thus serves as a crucial negative regulator of the allogeneic immune response. In addition, she found out that patients who carry a polymorphism in the gene for miR-146a and thus express less miR?146a have a higher risk of contracting severe GvHD following allo-HSCT. The genotypic characterization of this polymorphism could thus potentially be used to identify high-risk patients. The findings were published in the journal and selected for presentation at the annual meeting of the American Society of Hematology. Currently, Stickel is studying whether miR-146a also plays a role in the recipient of an allo-HSCT and which immune cells are affected in this context.