Research Division of Physiological Chemistry I
We use mass spectrometry for studying various processes of biological and medical importance. The Division consists of the Molecular Biometry research group, proteomics core facility PK/KI and Chemical proteomics facility, which is part of the national Bio-MS facility.
Proteomics is large-scale analysis of the expression levels of proteins and/or the occupancy their modifications. Proteomics can also quantitatively assess the stability of proteins against proteolysis or thermal unfolding.
Our goal is to perfect the proteomics analysis and expand its application to a broad range of biomedical problems. We envision time when proteomics analyses will be widely used in clinical practice. For helping KI researchers in addressing a broad range of biomedical problems with proteomics, we have established a proteomics core facility PK/KI (run by Dr. Akos Vegvari).
Central dogma of proteomics
We formulated the “Central dogma of proteomics” which postulates that important biological processes almost inevitably involve changes in the expression levels, PTM occupancies or stability of the proteins involved in these processes.
We are also strong believers in Chemical proteomics, which studies by proteomics methods:
- The effects of small molecules, e.g. drugs, on cells and organisms.
- The properties of proteins using small molecules as probes.
One of the predictions of the Central dogma of proteomics is that when a small-molecule drug kills mammalian cells (e.g. anticancer drug applied to cancer cells), the proteins whose expression changes the most are the drug target proteins. Empirical observations confirm this prediction, which forms the basis of the Functional Identification of Targets by Expression proteomics (FITExP). FITExP is one of the methods we are widely applying in Chemical proteomics projects. The other method is Thermal Proteome Profiling (TPP).
In order to improve proteomics analysis, we have developed a novel tool for in-solution, on-line separation of proteins and peptides by their isolelectric point (pI). Under the commercial name “pI-Trap”, this tool is now being produced by Biomotif AB.
With the help of this tool we have verified the “pI≈7.4 hypothesis”. It postulates that in human blood, the pI region around 7.4 (corresponds to blood pH) is rich with abnormal proteoforms, which are suitable as biomarkers of e.g. neurodegenerative diseases.
We have developed a number of popular Open source tools for protein quantification – Quanti and DeMix Q for label-free analysis and a more general Diffacto. Prof. Lukas Käll was an important collaborator in the last two projects.
We have initiated two series of annual international conferences:
- Uppsala Conference on Electron Capture/Transfer Dissociation and Related Phenomena (UppCon) – since 2003
- Pathway Analysis in Proteomics (PathProt) – since 2008
Research groups and core facilities
- Molecular Biometry research group (Roman Zubarev group)
- Proteomics Karolinska (PK/KI)
- Chemical Proteomics core facility