Mainz, Germany – The protein TDP-43 is present in all cells of our body and important for their biochemical processes. However, this protein can aggregate into large clumps in the brain, which can cause degenerative diseases such as Alzheimer’s and other dementias. How exactly this happens and how these protein clumps are linked to disease is a subject of intense research. Professor Dorothee Dormann of Johannes Gutenberg University Mainz (JGU) suspects that these proteins may also assemble in healthy cells – and that this assembly on a much smaller scale is important for the normal function of the TDP-43 protein. Her research group investigates the reason for these assemblies in the TDP Assembly project, for which the European Research Council has now awarded her an ERC Consolidator Grant worth EUR 2 million. This is one of the EU’s most prestigious and valuable grants, awarded to outstanding individual scientists working on ground-breaking research. Dorothee Dormann is Professor of Molecular Cell Biology at JGU and Adjunct Director at the Institute of Molecular Biology (IMB) in Mainz.
Smaller assemblies of TDP-proteins are important for regulatory processes in the cell
Dormann’s preliminary work indicates that smaller assemblies of TDP-43 proteins could play an important role in the cell’s regulatory processes such as in the reading of genetic information and RNA production, for example. Using methods from synthetic biology, she aims to artificially trigger various TDP-43 assemblies and investigate the resulting changes in cells. “The aim is to understand both the normal assembly process in healthy cells and the changes that lead to degenerative diseases when the assemblies become too large or too solid,” explained Dormann. Such abnormal protein clumps not only cause problems in the brain but also lead to a malfunction of the regulatory processes that the smaller assemblies normally carry out. In her research, Dormann will address the question of consequences of losing these small TDP-43 assemblies.
This research is especially important for developing future drugs to treat neurodegenerative diseases because drugs that prevent the aggregation of TDP-43 may also interfere with the smaller TDP-43 assemblies that are important for the body. A precise understanding of the functions of the assemblies is therefore required as well as knowledge of how the assembly process can be controlled from the early stages to the formation of large aggregates.
Top-level research in the field of neurodegenerative diseases
Dorothee Dormann studied biochemistry at the University of Tübingen and the University of North Carolina. She completed her doctorate at The Rockefeller University in New York and did post-doctoral research at LMU in Munich. From 2014 to 2021, she was head of an Emmy Noether Junior Research Group at the Biomedical Center (BMC) at LMU Munich. Since April 2021, she has been Professor of Molecular Cell Biology at Johannes Gutenberg University Mainz and Adjunct Director at the Institute of Molecular Biology (IMB) in Mainz. Dormann is co-spokesperson of the Collaborative Research Center “Polymer Concepts for Understanding Cellular Functions” (CRC 1551) and spokesperson of its integrated Research Training Group, both funded by the German Research Foundation. She is also a Principal Investigator in the research network EMTHERA (Emerging therapeutic strategies against infections, inflammation, and immune-mediated diseases), with which Mainz University is applying for funding as a Cluster of Excellence in the German Excellence Strategy competition. Dormann has received numerous awards for her research achievements, including the Heinz Maier-Leibnitz Prize 2014 and the Paul Ehrlich and Ludwig Darmstaedter Prize for Young Researchers 2019.
The ERC Consolidator Grant
The ERC Consolidator Grant is one of the most valuable EU funding schemes awarded to individual researchers. Through these grants, the European Research Council (ERC) supports outstanding scientists within seven to twelve years after completing their doctorate. Successful applicants must not only demonstrate excellence in research but also provide evidence of the groundbreaking nature and feasibility of their project. The funding period spans five years.
The European Research Council has also approved two other ERC Consolidator Grants at JGU: Professor Shuqing Xu’s project on the evolution of ecosystems in climate change and Professor Sebastian Erdweg’s project on the energy-efficient execution of reactive software systems. Furthermore, JGU-based palaeogeneticist Professor Joachim Burger is involved in an ERC Consolidator Grant project researching the adaptation of historical populations to urban life, which is coordinated by Professor Christina Papageorgopoulou from Democritus University of Thrace.