Development and Application of Mass Spectrometry Imaging to Biological Models.

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Information about the distribution of drugs and pesticides and their metabolites in tissues is important for understanding and predicting a chemical's action and toxicity. Mass Spectrometry Imaging (MSI) has emerged as an important tool in the last decade and it is beginning to show potential to provide new information in many fields owing to its unique ability to acquire molecularly specific images and to provide multiplexed information without the need for labeling or staining. In MSI, the chemical identity of molecules present on a surface is investigated as a function of their spatial distribution. In addition to now standard methods involving MSI in vacuum such as matrix-assisted laser desorption ionization (MALDI) and secondary-ion mass spectrometry (SIMS), recently developed ambient ionization techniques, such as desorption electrospray ionization (DESI) and desorption atmospheric pressure photoionization (DAPPI), allow MSI under atmospheric pressure of untreated samples outside the mass spectrometer. We propose the development and application of MSI to biological models of drug/pesticide distribution in biological tissues. Specifically, we will characterize the zebrafish as a biological model for studies of drugs/pesticides or chemical vector systems to achieve targeted therapy and toxicological analysis by MSI. We also will investigate different materials for direct or indirect analysis of chemical mediators released when different strains of bacteria interact. This project is of great interest to pharmaceutical companies trying to better track metabolites of drugs in specific tissues or to identify and understand chemical mediators in bacterial interactions. The work would benefit both academics and pharmaceutical companies, helping in the elucidation of the biochemical/toxicological pathways and, assist future structure-ADME studies for the development of new molecules with better activity and less toxicity. Moreover, in the future this project could help environmental monitoring by analyzing drugs and pesticides in wild animals and find new potential antibiotics to treat bacterial infections.