High resolution mass spectrometer for RNomics

• Subject Area: Medicine
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 567203826

RNA and proteins share various attributes, including their transient and thus dynamic nature. Both molecules are chemically decorated by dedicated enzymes and the resulting modifica-tions are crucial for the function of both biomolecules. While research of proteins and its mod-ifications is dominated by mass spectrometry (MS) of partial protein hydrolysates (e.g. tryptic digests), a similar technology for partial RNA hydrolysates is only just developing and pio-neered by the Kaiser Lab at Goethe-University Frankfurt. The analysis of post-translational protein modifications using quantitative MS has revolutionized our understanding of epigenetic regulation. For the equally important epitranscriptomics (RNA modifications of a cell), a com-parable MS method has been completely lacking, although RNAs are hotspots of post-tran-scriptional modification that have essential functions in the regulation of cellular homeostasis and are frequently associated with cancer and neurological diseases. With the equipment procured by DFG and co-financed by EFRE, the Kaiser Lab will develop technologies that enable MS-based sequencing and direct analysis of RNA modifications de-rived from cellular lysates for the first time. We will use the technological advances we have already made to enable MS-based epitranscriptome analysis on instruments commonly used for proteomic MS. This will enable epitranscriptome analysis to be accessible to any laboratory performing proteome analysis. The resulting technological innovation will create a multiplier effect for international epitranscriptome research. This will make it possible to map and under-stand the human RNome (the entirety of all RNA in a human cell including its modifications) and to modulate it with drugs. This is tantamount to a revolution in biomedical research, the foretaste of which we experienced when a modified RNA ended the pandemic (mRNA vaccine BioNTech and Moderna). In addition to the direct benefits for human health, the epitranscrip-tome has great potential in agriculture, where yields could be increased with the help of RNA modification. Here, we apply for funding of a modern “omics” device (nanoflow HRMS) to continue our efforts in pioneering an “RNomics” technology. The new instrument is urgently needed because (1) the current system is already 8 years old and repeatedly out-of-service due to instrument age-related breakdowns with costs exceeding 50T €/a, (2) is often not sensitive enough for detec-tion of low abundant RNAs from cell lysates and (3) is run at full capacity handling both prote-omics and RNomics analyses.

• DFG Programme: Major Research Instrumentation
• Major Instrumentation: Hochauflösendes Massenspektrometer für RNomics
• Instrumentation Group: 1700 Massenspektrometer
• Applicant Institution: Goethe-Universität Frankfurt am Main
• Leader: Professorin Dr. Stefanie Kaiser