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Wednesday, 09 December, 2020

Two ERC grants for CeNS members

Jan Lipfert and Ralf Jungmann receive Consolidator Grants

 

The European Research Council (ERC) has awarded six of its Consolidator Grants to researchers at LMU.

CeNS members Jan Lipfert and Ralf Jungmann have been awarded Consolidator Grants in the latest evaluation of research proposals submitted to the ERC. The awards are worth up to 2 million euros over the course of 5 years. The ERC’s Consolidator Grants are intended to enable highly qualified academics to further extend their innovative research programs. The ERC’s decisions are based solely on the scientific stature of the applicant and the intrinsic quality of the proposed project.

Ralf Jungmann is Professor for Experimental Biophysics at LMU Munich and head of the research group “Molecular Imaging and Bionanotechnology” at the Max Planck Institute of Biochemistry in Martinsried.

One of the major aims of many therapeutics is targeting cell surface proteins to alter cellular behavior. Recently approved immunotherapeutic drugs trigger anti-tumor immunity by disrupting key cell surface proteins that guide immune cell interactions. Despite the cell surface representing a major site of drug action, its nanoscale organization remains poorly characterized. The main reason for this is largely due to technical limitations of fluorescence imaging approaches. Current techniques do not allow high-throughput measurements of the spatial localization and interaction of hundreds of proteins with true single-protein-resolution on cell surfaces. With the ERC Consolidator Grant “ReceptorPAINT – Imaging Receptomics as a tool for biomedical discovery”, Jungmann and his research team aim to develop novel imaging technologies based on DNA-PAINT microscopy to enable the visualization and quantification of all relevant cell surface proteins at single-protein-resolution. To achieve this, the scientists plan to increase spatial resolution, develop DNA-based protein binders against all cell surface proteins, and devise multiplexing capabilities to resolve them with single-protein-resolution over large fields of view. The researchers will then use these new capabilities to map the nanoscale organization of hundreds of key immunomodulatory surface proteins and their corresponding ligands on key interacting pairs of immune cells relevant to current immunotherapy approaches. Jungmann wants to test the central hypothesis that surface protein architecture and patterning on immune and tumor cells dictates the outcome of their interactions. The techniques could yield fundamental insights into the molecular architecture of immune cell interactions and enable the future development of more refined “pattern”-based immunotherapeutics.

Ralf Jungmann studied physics at Saarland University and the University of California in Santa Barbara and received his doctorate at the Technical University of Munich. He then worked as a post-doctoral fellow at Harvard University, USA. In 2014 he moved to Munich to head the Emmy Noether research group “Molecular Imaging and Bionanotechnology” at the MPI of Biochemistry and the Faculty of Physic of the LMU. Since 2016, Ralf Jungmann has been Professor of Experimental Physics at LMU.

Jan Lipfert is Professor of Experimental Physics at LMU Munich. He is interested in the function, dynamics and interactions of biological macromolecules, with a particular focus on how their structures and functions are altered under the influence of external forces.

Mechanical forces play critical roles in the regulation of many essential biological processes. For example, the signaling pathways that control primary hemostasis and the initiation of blood coagulation are activated by changes of the flow pattern in the blood stream. Such changes alter the conformations of the blood glycoprotein von Willebrand factor, which in turn exposes cryptic binding sites and triggers downstream events that activate hemostasis. Perturbations of mechanoregulation can result in disorders including cancers and heart attacks. The processes that control responses to forces at the level of the mechanosensitive proteins are poorly understood, partly because the forces involved are very small, and therefore difficult to measure. Jan Lipfert‘s ERC project ProForce (“Mechano-Regulation of Proteins at Low Forces: Paving the Way for Therapeutic Interventions”) is designed to provide a solution to this problem. He will develop massively parallel magnetic tweezers, which are able to exert and precisely quantify miniscule forces (<0.1 picoNewtons) and therefore provide ideal tools for the measurement of the mechanical forces to which single proteins are exposed. Lipfert plans to use such an instrument to study mechanoregulation in biological systems in detail, and to develop pharmaceutical strategies for correcting disease states caused by abnormal responses of mechanosensitive proteins to ambient forces. The project will focus on three model proteins that respond to very weak mechanical forces, and are involved in blood coagulation, cell proliferation and carcinogenesis, respectively.

Jan Lipfert studied Physics and Economics at Heidelberg University. He went on to obtain Master’s degrees at Uppsala University and the University of Illinois in Urbana-Champaign, respectively, and earned his PhD at Stanford University in 2008. After a stint as a postdoc at the Technical University in Delft, he was appointed to his present position as Professor of Experimental Physics with a focus on Biophysics at the LMU Munich in 2013