Spatial Mass Spectrometry

Description

Our research group (PI, Prof. Per Andrén) uses mass spectrometry imaging (MSI) to study the spatial localization of small endogenous compounds, e.g., neurotransmitters, metabolites, lipids, peptides, proteins, as well as drugs and their metabolites in biological tissue sections. Our main focus is to study neurochemical processes in Parkinson's disease (PD), specifically L-Dopa-induced dyskinesia (LID), Lewy body dementia (LBD) and PD dementia. Besides our own research activities, we are also part of the SciLifeLab platform Spatial Biology, collaborating with both academic researchers and industry. Erik Jansson (Assistant Professor, PI) leads a team working on method development for proteomic analysis. His team studies in particular, protein structure with hydrogen–deuterium exchange, and does biochemical pathway identification with thermal proteome profiling.

Mass spectrometry imaging (MSI) is a novel technique used to determine the spatial distribution of neurotransmitters, peptides, small proteins, drugs and metabolites in situ in biological tissue sections. The technology enables highly specific analysis, visualization and quantitation of numerous molecules simultaneously and in their native biochemical state, within the same tissue section. We use matrix-assisted laser desorption ionization (MALDI) and desorption electrospray ionization (DESI) imaging techniques. Our laboratory is equipped with the latest technology and instrumentation for MSI.

Exploration of neurochemical changes associated with L-DOPA-induced dyskinesia in Parkinson´s disease. L-DOPA-induced dyskinesia is one of the most challenging problems facing patients with Parkinson’s disease (PD). The aim of this project is to elucidate the underlying pathophysiological mechanisms involved by studying different PD animal models, as well as human postmortem brains and cerebrospinal fluid. We simultaneously image and quantify comprehensive neurotransmitter and neuropeptide systems, metabolites, lipids, and proteins directly in brain tissue sections.

Spatial omics enable improved pathophysiology-based diagnosis of Parkinson's disease dementia and dementia with Lewy bodies. This interdisciplinary research project aims to understand Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (LBD) by finding pathophysiological mechanisms, and to develop diagnostic and prognostic tests that can differentiate between the two diseases. No chemical test currently exists to diagnose PD, PDD and LBD. We examine human post-mortem tissue and wet clinical samples and we combine spatially resolved transcriptomics, spatial proteomics and spatial mass spectrometry with bioinformatics to identify diagnostic and predictive biomarkers.

MSI provides novel information in drug research and development. MSI enables visualization and quantitation of distributions of diverse molecules at high lateral resolution in studies of the pharmacokinetic and pharmacodynamic (PK/PD) effects of drugs on functional biomolecules. The aim of this project is to develop strategies and use MSI in PK/PD, safety toxicology and blood-brain barriers drug research.