ASU Electronic Theses and Dissertations
This collection includes most of the ASU Theses and Dissertations from 2011 to present. ASU Theses and Dissertations are available in downloadable PDF format; however, a small percentage of items are under embargo. Information about the dissertations/theses includes degree information, committee members, an abstract, supporting data or media.
In addition to the electronic theses found in the ASU Digital Repository, ASU Theses and Dissertations can be found in the ASU Library Catalog.
Dissertations and Theses granted by Arizona State University are archived and made available through a joint effort of the ASU Graduate College and the ASU Libraries. For more information or questions about this collection contact or visit the Digital Repository ETD Library Guide or contact the ASU Graduate College at gradformat@asu.edu.
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- All Subjects: Biology
- Creators: Wang, Xiao
Description
Random peptide microarrays are a powerful tool for both the treatment and diagnostics of infectious diseases. On the treatment side, selected random peptides on the microarray have either binding or lytic potency against certain pathogens cells, thus they can be synthesized into new antimicrobial agents, denoted as synbodies (synthetic antibodies). On the diagnostic side, serum containing specific infection-related antibodies create unique and distinct "pathogen-immunosignatures" on the random peptide microarray distinct from the healthy control serum, and this different mode of binding can be used as a more precise measurement than traditional ELISA tests. My thesis project is separated into these two parts: the first part falls into the treatment side and the second one focuses on the diagnostic side. My first chapter shows that a substitution amino acid peptide library helps to improve the activity of a recently reported synthetic antimicrobial peptide selected by the random peptide microarray. By substituting one or two amino acids of the original lead peptide, the new substitutes show changed hemolytic effects against mouse red blood cells and changed potency against two pathogens: Staphylococcus aureus and Pseudomonas aeruginosa. Two new substitutes are then combined together to form the synbody, which shows a significantly antimicrobial potency against Staphylococcus aureus (<0.5uM). In the second chapter, I explore the possibility of using the 10K Ver.2 random peptide microarray to monitor the humoral immune response of dengue. Over 2.5 billion people (40% of the world's population) live in dengue transmitting areas. However, currently there is no efficient dengue treatment or vaccine. Here, with limited dengue patient serum samples, we show that the immunosignature has the potential to not only distinguish the dengue infection from non-infected people, but also the primary dengue infection from the secondary dengue infections, dengue infection from West Nile Virus (WNV) infection, and even between different dengue serotypes. By further bioinformatic analysis, we demonstrate that the significant peptides selected to distinguish dengue infected and normal samples may indicate the epitopes responsible for the immune response.
ContributorsWang, Xiao (Author) / Johnston, Stephen Albert (Thesis advisor) / Blattman, Joseph (Committee member) / Arntzen, Charles (Committee member) / Arizona State University (Publisher)
Created2013
Description
There has been considerable advancement in the algae research field to move algae production for biofuels and bio-products forward to become commercially viable. However, there is one key element that humans cannot control, the natural externalities that impact production. An algae cultivation system is similar to agricultural crop farming practices. Algae are grown on an area of land for a certain time period with the aim of harvesting the biomass produced. One of the advantages of using algae biomass is that it can be used as a source of energy in the form of biofuels. Major advances in algae research and development practices have led to new knowledge about the remarkable potential of algae to serve as a sustainable source of biofuel. The challenge is to make the price of biofuels from algae cost-competitive with the price of petroleum-based fuels. The scope of this research was to design a concept for an automated system to control specific externalities and determine if integrating the system in an algae cultivation system could improve the algae biomass production process. This research required the installation and evaluation of an algae cultivation process, components selection and computer software programming for an automated system. The results from the automated system based on continuous real time monitored variables validated that the developed system contributes insights otherwise not detected from a manual measurement approach. The implications of this research may lead to technology that can be used as a base model to further improve algae cultivation systems.
ContributorsPuruhito, Emil (Author) / Sommerfeld, Milton (Thesis advisor) / Gintz, Jerry (Thesis advisor) / Alford, Eddie (Committee member) / Arizona State University (Publisher)
Created2014
Description
Microalgae represent a potential sustainable alternative for the enhancement and protection of agricultural crops. The dry biomass and cellular extracts of Scenedesmus dimorphus were applied as a biofertilizer, a foliar spray, and a seed primer to evaluate seed germination, plant growth, and crop yield of Roma tomato plants. The dry biomass was applied as a biofertilizer at 50 g and 100 g per plant, to evaluate its effects on plant development and crop yield. Biofertilizer treatments enhanced plant growth and led to greater crop (fruit) production. Timing of biofertilizer application proved to be of importance - earlier 50 g biofertilizer application resulted in greater plant growth. Scenedesmus dimorphus culture, growth medium, and different concentrations (1%, 5%, 10%, 25%, 50%, 75%, 100%) of aqueous cell extracts were used as seed primers to determine effects on germination. Seeds treated with Scenedesmus dimorphus culture and with extract concentrations higher than 50 % (0.75 g ml-1) triggered faster germination - 2 days earlier than the control group. Extract foliar sprays of 50 ml and 100 ml, were obtained and applied to tomato plants at various extract concentrations (10%, 25%, 50%, 75% and 100%). Plant height, flower development and number of branches were significantly enhanced with 50 % (7.5 g ml-1) extracts. Higher concentration sprays led to a decrease in growth. The extracts were further screened to assess potential antimicrobial activity against the bacterium Escherichia coli ATCC 25922, the fungi Candida albicans ATCC 90028 and Aspergillus brasiliensis ATCC 16404. No antimicrobial activity was observed from the microalga extracts on the selected microorganisms.
ContributorsGarcia-Gonzalez, Jesus (Author) / Sommerfeld, Milton (Thesis advisor) / Steele, Kelly (Committee member) / Henderson, Mark (Committee member) / Arizona State University (Publisher)
Created2014
Description
Synthetic gene networks have evolved from simple proof-of-concept circuits to
complex therapy-oriented networks over the past fifteen years. This advancement has
greatly facilitated expansion of the emerging field of synthetic biology. Multistability is a
mechanism that cells use to achieve a discrete number of mutually exclusive states in
response to environmental inputs. However, complex contextual connections of gene
regulatory networks in natural settings often impede the experimental establishment of
the function and dynamics of each specific gene network.
In this work, diverse synthetic gene networks are rationally designed and
constructed using well-characterized biological components to approach the cell fate
determination and state transition dynamics in multistable systems. Results show that
unimodality and bimodality and trimodality can be achieved through manipulation of the
signal and promoter crosstalk in quorum-sensing systems, which enables bacterial cells to
communicate with each other.
Moreover, a synthetic quadrastable circuit is also built and experimentally
demonstrated to have four stable steady states. Experiments, guided by mathematical
modeling predictions, reveal that sequential inductions generate distinct cell fates by
changing the landscape in sequence and hence navigating cells to different final states.
Circuit function depends on the specific protein expression levels in the circuit.
We then establish a protein expression predictor taking into account adjacent
transcriptional regions’ features through construction of ~120 synthetic gene circuits
(operons) in Escherichia coli. The predictor’s utility is further demonstrated in evaluating genes’ relative expression levels in construction of logic gates and tuning gene expressions and nonlinear dynamics of bistable gene networks.
These combined results illustrate applications of synthetic gene networks to
understand the cell fate determination and state transition dynamics in multistable
systems. A protein-expression predictor is also developed to evaluate and tune circuit
dynamics.
complex therapy-oriented networks over the past fifteen years. This advancement has
greatly facilitated expansion of the emerging field of synthetic biology. Multistability is a
mechanism that cells use to achieve a discrete number of mutually exclusive states in
response to environmental inputs. However, complex contextual connections of gene
regulatory networks in natural settings often impede the experimental establishment of
the function and dynamics of each specific gene network.
In this work, diverse synthetic gene networks are rationally designed and
constructed using well-characterized biological components to approach the cell fate
determination and state transition dynamics in multistable systems. Results show that
unimodality and bimodality and trimodality can be achieved through manipulation of the
signal and promoter crosstalk in quorum-sensing systems, which enables bacterial cells to
communicate with each other.
Moreover, a synthetic quadrastable circuit is also built and experimentally
demonstrated to have four stable steady states. Experiments, guided by mathematical
modeling predictions, reveal that sequential inductions generate distinct cell fates by
changing the landscape in sequence and hence navigating cells to different final states.
Circuit function depends on the specific protein expression levels in the circuit.
We then establish a protein expression predictor taking into account adjacent
transcriptional regions’ features through construction of ~120 synthetic gene circuits
(operons) in Escherichia coli. The predictor’s utility is further demonstrated in evaluating genes’ relative expression levels in construction of logic gates and tuning gene expressions and nonlinear dynamics of bistable gene networks.
These combined results illustrate applications of synthetic gene networks to
understand the cell fate determination and state transition dynamics in multistable
systems. A protein-expression predictor is also developed to evaluate and tune circuit
dynamics.
ContributorsWu, Fuqing (Author) / Wang, Xiao (Thesis advisor) / Haynes, Karmella (Committee member) / Marshall, Pamela (Committee member) / Nielsen, David (Committee member) / Brafman, David (Committee member) / Arizona State University (Publisher)
Created2017
Description
Phytoplankton comprise the base of the marine food web, and, along with heterotrophic protists, they are key players in the biological pump that transports carbon from the surface to the deep ocean. In the world's subtropical oligotrophic gyres, plankton communities exhibit strong seasonality. Winter storms vent deep water into the euphotic zone, triggering a surge in primary productivity in the form of a spring phytoplankton bloom. Although the hydrographic trends of this "boom and bust" cycle have been well studied for decades, community composition and its seasonal and annual variability remains an integral subject of research. It is hypothesized here that proportions of different phytoplankton and protistan taxa vary dramatically between seasons and years, and that picoplankton represent an important component of this community and contributor to carbon in the surface ocean. Monthly samples from the Bermuda Atlantic Time-series Study (BATS) site were analyzed by epifluorescence microscopy, which permits classification by morphology, size, and trophic type. Epifluorescence counts were supplemented with flow cytometric quantification of Synechococcus, Prochlorococcus, and autotrophic pico- and nanoeukaryotes. Results from this study indicate Synechococcus and Prochlorococcus, prymnesiophytes, and hetero- and mixotrophic nano- and dinoflagellates were the major players in the BATS region plankton community. Ciliates, cryptophytes, diatoms, unidentified phototrophs, and other taxa represented rarer groups. Both flow cytometry and epifluorescence microscopy revealed Synechococcus to be most prevalent during the spring bloom. Prymnesiophytes likewise displayed distinct seasonality, with the highest concentrations again being noted during the bloom. Heterotrophic nano- and dinoflagellates, however, were most common in fall and winter. Mixotrophic dinoflagellates, while less abundant than their heterotrophic counterparts, displayed similar seasonality. A key finding of this study was the interannual variability revealed between the two years. While most taxa were more abundant in the first year, prymnesiophytes experienced much greater abundance in the second year bloom. Analyses of integrated carbon revealed further stark contrasts between the two years, both in terms of total carbon and the contributions of different groups. Total integrated carbon varied widely in the first study year but displayed less fluctuation after June 2009, and values were noticeably reduced in the second year.
ContributorsHansen, Amy (Author) / Neuer, Susanne (Thesis advisor) / Krajmalnik-Brown, Rosa (Committee member) / Sommerfeld, Milton (Committee member) / Arizona State University (Publisher)
Created2010
Description
Fusion proteins that specifically interact with biochemical marks on chromosomes represent a new class of synthetic transcriptional regulators that decode cell state information rather than deoxyribose nucleic acid (DNA) sequences. In multicellular organisms, information relevant to cell state, tissue identity, and oncogenesis is often encoded as biochemical modifications of histones, which are bound to DNA in eukaryotic nuclei and regulate gene expression states. In 2011, Haynes et al. showed that a synthetic regulator called the Polycomb chromatin Transcription Factor (PcTF), a fusion protein that binds methylated histones, reactivated an artificially-silenced luciferase reporter gene. These synthetic transcription activators are derived from the polycomb repressive complex (PRC) and associate with the epigenetic silencing mark H3K27me3 to reactivate the expression of silenced genes. It is demonstrated here that the duration of epigenetic silencing does not perturb reactivation via PcTF fusion proteins. After 96 hours PcTF shows the strongest reactivation activity. A variant called Pc2TF, which has roughly double the affinity for H3K27me3 in vitro, reactivated the silenced luciferase gene by at least 2-fold in living cells.
ContributorsVargas, Daniel A. (Author) / Haynes, Karmella (Thesis advisor) / Wang, Xiao (Committee member) / Mills, Jeremy (Committee member) / Arizona State University (Publisher)
Created2019
Description
A notable challenge when assembling synthetic gene circuits is that modularity often fails to function as intended. A crucial underlying reason for this modularity failure is the existence of competition for shared and limited gene expression resources. By designing a synthetic cascading bistable switches (Syn-CBS) circuit in a single strain with two coupled self-activation modules to achieve successive cell fate transitions, nonlinear resource competition within synthetic gene circuits is unveiled. However, in vivo it can be seen that the transition path was redirected with the activation of one switch always prevailing over that of the other, contradictory to coactivation theoretically expected. This behavior is a result of resource competition between genes and follows a ‘winner-takes-all’ rule, where the winner is determined by the relative connection strength between the two modules. Despite investigation demonstrating that resource competition between gene modules can significantly alter circuit deterministic behaviors, how resource competition contributes to gene expression noise and how this noise can be controlled is still an open issue of fundamental importance in systems biology and biological physics. By utilizing a two-gene circuit, the effects of resource competition on protein expression noise levels can be closely studied. A surprising double-edged role is discovered: the competition for these resources decreases noise while the constraint on resource availability adds its own term of noise into the system, denoted “resource competitive” noise. Noise reduction effects are then studied using orthogonal resources. Results indicate that orthogonal resources are a good strategy for eliminating the contribution of resource competition to gene expression noise.
Noise propagation through a cascading circuit has been considered without resource competition. It has been noted that the noise from upstream genes can be transmitted downstream. However, resource competition’s effects on this cascading noise have yet to be studied. When studied, it is found that resource competition can induce stochastic state
switching and perturb noise propagation. Orthogonal resources can remove some of the resource competitive behavior and allow for a system with less noise.
ContributorsGoetz, Hanah Elizabeth (Author) / Tian, Xiaojun (Thesis advisor) / Wang, Xiao (Committee member) / Lai, Ying-Cheng (Committee member) / Arizona State University (Publisher)
Created2022