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Applying Quantitative Super-Resolution Microscopy to Probe Molecular Organization of Membrane Proteins
Başlık:
Applying Quantitative Super-Resolution Microscopy to Probe Molecular Organization of Membrane Proteins
Yazar:
Tobin, Steven Jeffrey, author.
ISBN:
9780438056336
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (202 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-10(E), Section: B.
Advisors: Tijana Jovanović-Talisman Committee members: Michael Barish; David D. Lo; Nagarajan Vaidehi; John C. Williams.
Özet:
Super-resolution microscopy is a powerful technique that allows researchers to investigate cellular features with single molecule sensitivity and nanoscale precision. Herein, I use quantitative pointillistic super-resolution microscopy (also referred to as a single molecule localization microscopy, SMLM) to characterize the density and nano-organization of membrane proteins. In particular, I use Photoactivated Localization Microscopy or direct Stochastic Optical Reconstruction Microscopy to image membrane proteins and apply pair-correlation analysis to analyze these images. This thesis focuses on two main projects: 1) investigating the molecular signatures of opioid receptors in response to ethanol and 2) characterizing the density and nanoscale organization of human epidermal growth factor receptor 2 (HER2) in breast cancer patients. In my first project, I show that treatment with physiologically relevant concentrations of ethanol leads to the redistribution of lipid raft marker glycosylphosphatidylinositol (GPI), actin, and mu- and kappa-opioid receptors (MOR and KOR, respectively). I demonstrate that the opioid receptor antagonist naltrexone has a preventative effect on ethanol-induced rearrangements of GPI and MOR. Interestingly, naltrexone significantly affects KOR organization. Based on these data, a new model for ethanol/naltrexone action on opioid receptors is proposed. In my second project, I show that quantitative SMLM can be used as a diagnostic tool to report the status of HER2 in breast cancer tumors. Results, for three cultured cell lines and five patient tissue samples, indicate that HER2 copy numbers from fluorescence in situ hybridization significantly correlate with detected densities from quantitative SMLM. Cumulatively, results from these two projects suggest that quantitative SMLM techniques can effectively aid in biomedical research. In the case of imaging opioid receptors, a better understanding of the underlying mechanisms involved in alcohol abuse disorders could help in the development of more effective molecular interventions. Illustrated by my second project on HER2-positive tissue, molecular details from cancer biomarkers (via SMLM) could be instrumental in establishing more personalized patient treatments.
Notlar:
School code: 0517
Mevcut:*
Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(682590.1) | 682590-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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