cUMP, a novel second messenger

• Applicant: Professor Dr. Roland Seifert
• Subject Area: Pharmacology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 530200718

The functions of all cells of the human body are regulated by hormones and neurotransmitters (first messengers) and transmitted inside the cell by second messengers. The second messengers include the nucleotides cyclic-AMP (cAMP) and cyclic-GMP (cGMP). In many diseases, the balance of these second messengers is disturbed, and accordingly, many drugs work to restore the balance. The importance of cAMP and cGMP is reflected in the fact that several Nobel Prizes were awarded for this field. A few years ago, the second messengers cyclic-UMP (cUMP) and cyclic-CMP (cCMP) were identified. The importance of these signaling molecules for the regulation of bodily functions is still largely unknown. However, the fact that various bacterial toxins produce cUMP and cCMP suggests that these second messengers play a role in infectious diseases. This assumption is also supported by the fact that in bacteria, there is a large number of enzymes that produce either cUMP or cCMP. In bacteria, cCMP and cUMP play a role especially in the defense against viral infections. Against this background, a consortium of scientists from France and Germany has formed to elucidate the function of cUMP and cCMP. First, specific fluorescence sensors will be developed with which it will become possible to precisely track these second messengers in cells. This is also an important prerequisite for other researchers to be able to investigate the exact function of cUMP and cCMP in the various body cells. In addition, we will use specific probes to detect the target structures of cUMP and cCMP in cells. This is an important prerequisite for being able to influence these target structures in diseases. Finally, we will investigate with high resolution the structure of the enzymes that produce these second messengers. This is also an important prerequisite for being able to influence these signaling pathways with drugs. In summary, this Franco-German consortium has come together to join forces to launch a pioneering project in a new and hitherto poorly understood field of biology. Based on the experience with cAMP and cGMP as well as the preliminary findings with bacterial toxins, we can assume that the cUMP/cCMP system is of great importance for normal functions of the human body and diseases. In the long term, the project creates the basis for the development of new drugs for diseases such as bacterial infections, which cannot be treated anymore with conventional drugs ("antibiotics").

• DFG Programme: Research Grants
• International Connection: France
• Cooperation Partners: Dr. Undine Mechold; Dr. Louis Renault