Theses and Dissertations
This collection includes both ASU Theses and Dissertations, submitted by graduate students, and the Barrett, Honors College theses submitted by undergraduate students.
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Description
As Alzheimer’s disease (AD) increases in incidence, there is an increased investigation into the pathogenesis of the disease in hopes of finding a cure to the neurodegenerative disease. The two key hallmarks of AD consist of amyloid beta plaques and hyperphosphorylated tau fibrillary tangles. Amyloid beta is a peptide that is proteolytically cleaved from the type I transmembrane glycolytic amyloid precursor protein (APP). APP is highly conserved across species, suggesting the importance of APP in healthy brain functioning. However, when APP is cleaved through the amyloidogenic pathway it produces amyloid beta. The trafficking of APP within neurons has been a new endeavor for neurodegenerative disease research, as reduced retrograde trafficking of APP has been hypothesized to increase the likelihood of the amyloidogenic cleavage of APP, resulting in increased amyloid beta presence (Ye et al., 2017). The findings of this study suggest that transport of APP within neurons is significantly inhibited by increased extracellular glutamate concentration. The addition of human primary astrocytes within a human neuron co-culture allowed for significantly increased retrograde transport of APP within neurons, even within high glutamate conditions. These finding enhance the current field of research regarding astrocytes neuroprotective role within the brain, but bring attention to the role that astrocytes have upon regulation of the axonal transport of proteins within neurons.
ContributorsKlosterman, Katja Elisabeth (Author) / Ros, Alexandra (Thesis director) / Redding, Kevin (Committee member) / Watts College of Public Service & Community Solut (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-12
Description
Membrane proteins are a vital part of cellular structure. They are directly involved in many important cellular functions, such as uptake, signaling, respiration, and photosynthesis, among others. Despite their importance, however, less than 500 unique membrane protein structures have been determined to date. This is due to several difficulties with macromolecular crystallography, primarily the difficulty of growing large, well-ordered protein crystals. Since the first proof of concept for femtosecond nanocrystallography showing that diffraction patterns can be collected on extremely small crystals, thus negating the need to grow larger crystals, there have been many exciting advancements in the field. The technique has been proven to show high spatial resolution, thus making it a viable method for structural biology. However, due to the ultrafast nature of the technique, which allows for a lack of radiation damage in imaging, even more interesting experiments are possible, and the first temporal and spatial images of an undamaged structure could be acquired. This concept was denoted as time-resolved femtosecond nanocrystallography.
This dissertation presents on the first time-resolved data set of Photosystem II where structural changes can actually be seen without radiation damage. In order to accomplish this, new crystallization techniques had to be developed so that enough crystals could be made for the liquid jet to deliver a fully hydrated stream of crystals to the high-powered X-ray source. These changes are still in the preliminary stages due to the slightly lower resolution data obtained, but they are still a promising show of the power of this new technique. With further optimization of crystal growth methods and quality, injection technique, and continued development of data analysis software, it is only a matter of time before the ability to make movies of molecules in motion from X-ray diffraction snapshots in time exists. The work presented here is the first step in that process.
This dissertation presents on the first time-resolved data set of Photosystem II where structural changes can actually be seen without radiation damage. In order to accomplish this, new crystallization techniques had to be developed so that enough crystals could be made for the liquid jet to deliver a fully hydrated stream of crystals to the high-powered X-ray source. These changes are still in the preliminary stages due to the slightly lower resolution data obtained, but they are still a promising show of the power of this new technique. With further optimization of crystal growth methods and quality, injection technique, and continued development of data analysis software, it is only a matter of time before the ability to make movies of molecules in motion from X-ray diffraction snapshots in time exists. The work presented here is the first step in that process.
ContributorsKupitz, Christopher (Author) / Fromme, Petra (Thesis advisor) / Spence, John C. (Thesis advisor) / Redding, Kevin (Committee member) / Ros, Alexandra (Committee member) / Arizona State University (Publisher)
Created2014