The University of Cologne researchers Professor Dr Thorsten Hoppe and Professor Dr Jens Brüning have received the ERC Advanced Grant from the European Research Council. The ERC Advanced Grant, which provides 2.5 million euros in funding, is the most prestigious research prize of the European research landscape. “The highest personal award of the EU funding programme to two scientists shows that basic research pursuing important questions at the highest level is being conducted here at the University of Cologne. It is a great success for both of our scientists, who represent the field of biology at the University of Cologne,” said Professor Dr Joybrato Mukherjee, Rector of the University of Cologne.

Quality assurance of proteins prevents neurodegeneration

Professor Dr Thorsten Hoppe, Principal Investigator at the University of Cologne’s Cluster of Excellence for Aging Research CECAD, will receive funding of 2.5 million euros over a five-year period for his research project ‘Cellular Strategies of Protein Quality Control-Degradation’ (CellularPQCD). “We are very pleased about the funding that enables us to establish a new research topic of high medical relevance. With the help of the ERC Grant, we will investigate how discarded proteins are disposed of and recycled,” said Professor Dr Hoppe.

Maintaining the quality of all proteins is essential for the life of an organism, as it ensures tissue function, health and longevity. Protein quality control (PQC) is ensured by the controlled degradation of damaged proteins. This limits the formation of protein aggregates and neurodegeneration characteristic of Alzheimer’s, Huntington’s, and Parkinson’s. Important regulators of protein degradation are E3-ubiquitin ligases, which specifically remove damaged proteins. However, therapeutically relevant E3 ligases that specialize in this degradation (PQCD - PQC degradation) are largely unknown.

The degradation of damaged proteins is a dynamic process in which physiological and environmental factors must interact to overcome the stress-related accumulation and clumping of proteins. Despite progress in characterizing regulatory signals for protein degradation, the biggest challenge is to understand the mechanisms of PQCD pathways under acute and chronic stress conditions.

The overarching aim of the new research programme is therefore to elucidate the molecular basis of stress-related protein degradation, which is crucial for normal cell function and health. The role of E3-ubiquitin ligases is investigated with the help of mammalian cell cultures and the nematode Caenorhabditis elegans as a genetic model organism. Thorsten Hoppe and his team expect new molecular insights into stress-induced adaptation mechanisms and will lay the foundation for research into the neurodegenerative diseases triggered by chronic protein damage.

New drugs to treat obesity

Professor Dr Jens Brüning from the Institute for Genetics at the University of Cologne is also CECAD Principal Investigator and director of the Polyclinic for Endocrinology, Diabetology and Preventive Medicine at University Hospital Cologne, and director at the Max Planck Institute for Metabolism Research. He will also receive the ERC Advanced Grant, amounting to 2.5 million euros over five years, which is the highest personal award the European Union confers to researchers. His project ‘Deconstructing Hypothalamic Neurocircuit Architecture and Function in Metabolic Control during Health and Disease’ on neural circuits of metabolic control could open up new avenues for the discovery of drugs to treat obesity and related metabolic diseases.

The number of overweight and obese people is steadily increasing worldwide. This makes them more susceptible to obesity-related diseases such as type 2 diabetes mellitus, cardiovascular disease, and certain cancers. It is therefore crucial to understand how our brain regulates and controls metabolism, what and how much we eat.

In his project, Brüning wants to identify new groups of nerve cells that control metabolic processes in the hypothalamus, the central circuit in the brain. In particular, he focuses on the circuits that control the transition from fasting to eating and which are activated in the development of obesity. He will also investigate how the nerve cells themselves change as obesity develops.

Research funding by the European Research Council

The ERC Advanced Grant is awarded to outstanding scholars and scientists for projects that promise ground-breaking results but carry a certain risk of failure due to the novelty of the chosen approach. To be eligible, candidates must apply with a European research institution and must have demonstrated excellent research results over at least ten years. The selection is largely based on the originality and the scientific impact of the expected contribution.
 

Media Contact:
Professor Dr Thorsten Hoppe
Aging Research Excellence Cluster CECAD
+49 221 478 84210
office-hoppeuni-koeln.de

Professor Dr Jens Brüning
Dr Maren Berghoff
Press and public relations
Max Planck Institute for Metabolic Research
Maren.berghoffsf.mpg.de
+49 +49 221 70 207

Press and Communications Teams:
Jan Voelkel
+49 221 470 2356
j.voelkelverw.uni-koeln.de

Further information:
https://erc.europa.eu/news-events/news/erc-2023-advanced-grants-results