Mass spectrometer LC-ESI-MS UHR QTOF

• Subject Area: Basic Research in Biology and Medicine
• Term: Funded in 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 438807818

Understanding the cellular processes of living systems requires a deep molecular understanding of the underlying biomolecules. Proteins play a key role in this because they are involved in all processes of the cell. The malfunction of proteins plays a significant role in many diseases.The approximately 20,000 genes of humans form the basis for the cellular production of approximately 500,000-1,000,000 different proteins and proteoforms. Proteoforms are modifications of an individual protein, which is converted into its physiologically active form by mostly biochemical changes. This alteration due to the chemical (covalent) linkage with small or large modifications.Both the production and the analysis of physiologically important proteoforms represent a considerable scientific hurdle. For the identification of a proteoform, the high-precision determination of the molecular mass is the most accurate and reliable method. This applies in particular the unambiguous assignment to different modification states. Modern ultra-high-resolution mass spectrometers guarantee this accuracy and have therefore revolutionized the molecular and systemic life sciences in recent decades.In the proposed project, we want to use an ultrahigh-resolution mass spectrometer to accurately map and determine proteoforms. We are interested in proteins that are isolated and characterized from their cellular context, as well manufactured purified protein and their complexes. We are particularly interested in proteins that are relevant in different diseases (such as bacterial infections). It is crucial that different modification states can be analyzed by mass spectrometry using intact proteins of various sizes. Since the mass changes due to protein modification are usually small, but the proteins themselves are relatively large, this analysis requires the latest generation of high-resolution mass spectrometers.We expect the requested device to enable us to identify and characterize proteoforms. It thus forms the basis for the understanding of the functional coupling of different modification sites in the cell, allows the validation of isolated or produced proteoforms in vitro and enables the quantitative investigation of enzymatic or chemical modification reactions. This will pave the way for us to understand the molecular importance of different proteoforms in health and disease.

• DFG Programme: Major Research Instrumentation
• Major Instrumentation: Massenspektrometer LC-ESI-MS UHR QTOF
• Instrumentation Group: 1700 Massenspektrometer
• Applicant Institution: Universität Hamburg
• Leader: Professor Dr. Aymelt Itzen