Groupe du Prof. Pierre Chaurand
Innovation in Mass Spectrometry Imaging
Matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI) is a powerful technique for determining the spatial distribution of analytes. Two distinct projects will be presented.
Novel derivatizing agents for steroidomics by MSI. Steroid dysregulation has been linked to pathology and can affect cell density and morphology. Mass spectrometry imaging (MSI) can allow for the mapping of steroids in tissue cross-sections. Traditionally, the low relative abundance and low ionization efficiency of steroids has prevented the detailed analysis of their distribution within tissues but the use of on-tissue chemical derivatization with novel derivatizing agents can overcome these challenges.
Transcription, proteomics and lipidomics correlation. Myelin basic protein (MBP) is the basic structural protein of myelin and is responsible for connecting the lipid layers of the myelin sheath. Demyelination is involved in several neurodegenerative diseases, including multiple sclerosis. Transcriptional regulation of MBP production was long thought to be controlled post-transcriptionally, as the abundance of myelin varies with factors such as cell size. To test this hypothesis, the enhancer region of the MBP gene was altered to generate a cohort of six mutant mouse lines with spinal cord MBP mRNA abundance varying from 122-25% of the wild type. In 90-day old mice, MBP levels were seen to vary from 120-5% of the wild-type abundance, showing a high correlation with mRNA levels. As MBP is a major component of myelin, other changes in molecular composition across all mutants were suspected. Most notably, lipidomic variations were expected, especially for cholesterol, as it makes up 44% of the lipid component of myelin. From MSI measurements, cholesterol levels remained stable for the single-knockout mutants but decreased up to 30% in the triple-knockout mutant. Phospholipid abundance also varied significantly across the cohort.
