Insights into metabolism and signaling at small scale

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Abstract/Contents

Abstract
Mass spectrometry is a powerful technique for the study of biological systems because it enables untargeted analysis of endogenous molecules, giving us insight into metabolism and signaling. Here we focus on ambient ionization methods for sampling, primarily desorption electrospray ionization imaging (DESI-MSI). We describe the adaptation of DESI-MSI for the imaging of small tissues, in particular murine adrenal glands under 2 mm in diameter and maize root primary tips less than 1 mm in diameter. We discuss the elements of probe construction, set-up, and image acquisition that influence the quality of measured DESI images. This contextualizes the modifications to the DESI probe and method that were made in order to resolve fine sub-tissue regions in these small tissues. The lateral spatial resolutions were also retroactively calculated for all imaged tissue sets in order to assess the influence of probe, step size, and sample material on spatial resolution. This work then describes two applications of DESI-MSI to small tissues. One is for targeted detection of succinate accumulation in the adrenal medulla in the development of a mouse model for succinate dehydrogenase (SDHx)-deficient pheochromocytoma. In this project, DESI-MSI detects a metabolic change that results from epigenetic silencing of genes which were not shown to be mutated by a genetic screen, suggesting further clinical applications of this technique. The second application of DESI-MSI is to the imaging of maize root cryosections, demonstrating this technique's potential for identifying small molecule regulators of root development. DESI imaging reveals not only metabolite gradients along the developmental axis, but also unique spatial patterning that correlates to known tissue sub-structures, including the inner vasculature and endodermis.

Description

Type of resource text
Form electronic resource; remote; computer; online resource
Extent 1 online resource.
Place California
Place [Stanford, California]
Publisher [Stanford University]
Copyright date 2021; ©2021
Publication date 2021; 2021
Issuance monographic
Language English

Creators/Contributors

Author Noll, Sarah Elizabeth
Degree supervisor Zare, Richard N
Thesis advisor Zare, Richard N
Thesis advisor Dai, Hongjie, 1966-
Thesis advisor Moerner, W. E. (William Esco), 1953-
Degree committee member Dai, Hongjie, 1966-
Degree committee member Moerner, W. E. (William Esco), 1953-
Associated with Stanford University, Department of Chemistry

Subjects

Genre Theses
Genre Text

Bibliographic information

Statement of responsibility Sarah E. Noll.
Note Submitted to the Department of Chemistry.
Thesis Thesis Ph.D. Stanford University 2021.
Location https://purl.stanford.edu/dx038hq9888

Access conditions

Copyright
© 2021 by Sarah Elizabeth Noll
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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