Biomolecular Imaging and Proteomics
Our research group focus on new approaches in mass spectrometry (MS), i.e. matrix-assisted laser desorption ionization MS imaging (MALDI-MSI) of biological tissue sections, and peptidomics, the comprehensive study of endogenous peptides.
Mass Spectrometry Imaging in Drug Discovery and Development – Targeting drugs, metabolites, peptides and neurotransmitters
Understanding the relationship between pharmacokinetics and pharmacodynamics is crucial in the development of effective drug therapies. Current technologies only provide information on the total amount of drug in the whole tissue with no possibility to address micro-environmental localization of the compound or metabolic derivatives. The application of MALDI-MSI in drug discovery studies provides a new tool to accurately measure local tissue concentrations of drug/drug metabolite in context with efficacy achieved with the targeted biology or in the context of safety.
The localization pattern from individual molecular species present on the tissue surface can then be extracted and positioned on the original histological image with the abundances represented by a concentration dependent color scale.
Peptidomics involves the comprehensive analysis of the endogenous peptide content of a certain cell, organ, body fluid, or organism. It complements molecular biology approaches in its ability to characterize the processing of translation products, including changes in expression or posttranslational modifications (PTMs) of peptides and small proteins. By comparing the proteins and peptides in samples of diseased tissue with those in normal tissue, differential expression patterns can be detected that may lead to the identification of novel biomarkers.
The objective of our research is to utilize MSI and peptidomics approaches to study neurochemical processes in Parkinson’s disease (PD) and specifically L-Dopa-induced dyskinesias (LID) (VR-M grant 2011-3170). The aim is to define neurotransmitters, neuropeptides and proteins that are differentially expressed in the basal ganglia complex of animals with striatal dopamine depletions, and to determine which of these neuropeptides and proteins are regulated by loss of dopamine signaling, as well as to investigate protein and peptide expression patterns in subjects with and without LID symptoms.
Our laboratory is equipped with the latest separation and MS technologies, i.e., two MALDI MSI TOF-TOF instruments (ultrafleXtreme, Bruker Daltonics; installed 2012 and 2014), one combined MALDI/ESI Q-Tof instrument (Synapt G2si; installed 2015) and two electrospray ionization mass spectrometers (LTQ, ThermoFischer Scientific; installed 2004) and a high-resolution Q-Tof mass spectrometer (Maxis Impact, Bruker Daltonics; installed 2012).