The overarching aim is to establish super-resolution-based techniques (PALM, STORM) to investigate protein aggregation in live cells. The so called fused in sarcoma (FUS) protein responsible for DNA/RNA binding, will be site specifically mutated to investigate its nuclear relocation and a potential aggregation in the cytosol.
Supervisors: Simon Mergenthal and Prof. Dr. Enrico Klotzsch
Location: Humboldt Universität zu Berlin, DE
T cells readily detect the presence of even a single antigenic peptide-major histocompatibility complexes (pMHC) complex and discriminate among thousands of endogenous pMHC via T cell receptors (TCRs) on the surface of antigen presenting cells. The mechanisms underlying this phenomenal sensitivity have remained elusive. Recent studies suggest mechanical forces to be instrumental in antigen sensing and discrimination. To address the role of forces and the origin of forces, we employ Traction Force Microscopy (TFM) into the immune synapse that allow us to quantitatively visualize forces acting between TCR and pMHC on opposing cell surfaces. Furthermore, we employ super-resolution microscopy to study simultaneous cytoskeletal remodeling. In summary, the project aims to understand, how mechanical forces orchestrates receptor-ligand interactions during immune synapse formation and T cell activation.
Supervisors: Tamara Zünd, Dr. Sebastian Lickert and Prof. Dr. Enrico Klotzsch
Location: D-HEST, ETH Zurich, CH
The overall aim of this proposed research is to establish optical super-resolution microscopy as a technique to connect mechanobiological aspects of T cell activation with altered gene expression. By combining cutting-edge imaging, mechanobiological and genetic tools, we will be able to answer the open question whether T cells use mechanical forces to distinguish between pathogens and furthermore, how these forces are transmitted into the nucleus to alter gene expression. This will be the first time a direct link between an extracellular cue and genetic regulation will be demonstrated and we will be able to dissect the mechanism.
Supervisors: Tamara Zünd, Dr. Sebastian Lickert and Prof. Dr. Enrico Klotzsch
Location: D-HEST, ETH Zurich, CH
If you would be interested in joining our lab and contribute to our research work, do not hesitate sending us directly your email motivation letter and cv.
Location: Humboldt Universität zu Berlin, DE
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