Proximity-Based Mass Spectrometry: Direct Detection and Characterization of Biomolecules

Abstract

Mass spectrometry (MS) is a powerful analytical tool that can be applied to the identification and characterization of biomolecules. Recent MS developments have expanded its use to include proximal detection which allows for the direct detection and characterization of biomolecules from their local microenvironment with minimal sample manipulation. The work embodied here centers upon two distinct projects that investigate outstanding biological questions using a combination of proximity-based MS and biology. The first project focuses on the direct detection of ovarian cancer, a severe gynecological disease, using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS analysis of vaginal lavage samples. A murine xenograft model was used in which cells were sourced from a local microenvironment for MALDI-TOF MS analysis. This proximal technique allowed for the detection of small proteins that were longitudinally significantly up- and down-regulated. The second project focuses on the cheese rind microbiome and the ability of its microbial population to produce antimicrobials. A series of three bacterial-fungal interactions are investigated for the production of antifungal or antibacterial metabolites using a combination of bioactivity assays and analytical tools.