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.
Displaying 1 - 10 of 19
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- All Subjects: Synthetic Biology
- All Subjects: Memory
- Creators: School of Life Sciences
Description
Nucleic acids encode the information required to create life, and polymerases are the gatekeepers charged with maintaining the storage and flow of this genetic information. Synthetic biologists utilize this universal property to modify organisms and other systems to create unique traits or improve the function of others. One of the many realms in synthetic biology involves the study of biopolymers that do not exist naturally, which is known as xenobiology. Although life depends on two biopolymers for genetic storage, it may be possible that alternative molecules (xenonucleic acids – XNAs), could be used in their place in either a living or non-living system. However, implementation of an XNA based system requires the development of polymerases that can encode and decode information stored in these artificial polymers. A strategy called directed evolution is used to modify or alter the function of a protein of interest, but identifying mutations that can modify polymerase function is made problematic by their size and overall complexity. To reduce the amount of sequence space that needs to be samples when attempting to identify polymerase variants, we can try to make informed decisions about which amino acid residues may have functional roles in catalysis. An analysis of Family B polymerases has shown that residues which are involved in substrate specificity are often highly conserved both at the sequence and structure level. In order to validate the hypothesis that a strong correlation exists between structural conservation and catalytic activity, we have selected and mutated residues in the 9°N polymerase using a loss of function mutagenesis strategy based on a computational analysis of several homologues from a diverse range of taxa. Improvement of these models will hopefully lead to quicker identification of loci which are ideal engineering targets.
ContributorsHaeberle, Tyler Matthew (Author) / Chaput, John (Thesis director) / Chen, Julian (Committee member) / Larsen, Andrew (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Currently in synthetic biology only the Las, Lux, and Rhl quorum sensing pathways have been adapted for broad engineering use. Quorum sensing allows a means of cell to cell communication in which a designated sender cell produces quorum sensing molecules that modify gene expression of a designated receiver cell. While useful, these three quorum sensing pathways exhibit a nontrivial level of crosstalk, hindering robust engineering and leading to unexpected effects in a given design. To address the lack of orthogonality among these three quorum sensing pathways, previous scientists have attempted to perform directed evolution on components of the quorum sensing pathway. While a powerful tool, directed evolution is limited by the subspace that is defined by the protein. For this reason, we take an evolutionary biology approach to identify new orthogonal quorum sensing networks and test these networks for cross-talk with currently-used networks. By charting characteristics of acyl homoserine lactone (AHL) molecules used across quorum sensing pathways in nature, we have identified favorable candidate pathways likely to display orthogonality. These include Aub, Bja, Bra, Cer, Esa, Las, Lux, Rhl, Rpa, and Sin, which we have begun constructing and testing. Our synthetic circuits express GFP in response to a quorum sensing molecule, allowing quantitative measurement of orthogonality between pairs. By determining orthogonal quorum sensing pairs, we hope to identify and adapt novel quorum sensing pathways for robust use in higher-order genetic circuits.
ContributorsMuller, Ryan (Author) / Haynes, Karmella (Thesis director) / Wang, Xiao (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
‘why we bend' a Bachelor of Fine Arts honors thesis exhibition by Ximenna Hofsetz and Tiernan Warner brings together installation, digital, sculptural, and printed artwork. The main focus concerns memory; and its vague, formless, and hazy nature. The work also examines what would happen if cognitive space could be physically mapped? What would it look like in sculptural form? Memory erodes and distorts with time. We influence our memories as much as they affect us. Thus, just as relationships are ever-changing, and our memories of those we interact with constantly shifting, our relationships with our own memories are malleable and evolve through time. This transient nature of memory is depicted in the various stylistic means of this exhibition by referencing time and space as well as personal memories and ephemera in both concrete and abstract ways. ‘why we bend’ implements a variety of multimedia techniques to examine recollection and its hold on us.
ContributorsHofsetz, Ximenna Cedella (Author) / Gutierrez, Rogelio (Thesis director) / Hood, Mary (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / School of Art (Contributor)
Created2014-12
Description
The ability to edit chromosomal regions is an important tool for the study of gene function and the ability to engineer synthetic gene networks. CRISPR-Cas systems, a bacterial RNA-guided immune system against foreign nucleic acids, have recently been engineered for a plethora of genome engineering and transcriptional regulation applications. Here we employ engineered variants of CRISPR systems in proof-of-principle experiments demonstrating the ability of CRISPR-Cas derived single-DNA-strand cutting enzymes (nickases) to direct host-cell genomic recombination. E.coli is generally regarded as a poorly recombinogenic host with double-stranded DNA breaks being highly lethal. However, CRISPR-guided nickase systems can be easily programmed to make very precise, non-lethal, incisions in genomic regions directing both single reporter gene and larger-scale recombination events deleting up to 36 genes. Genome integrated repetitive elements of variable sizes can be employed as sites for CRISPR induced recombination. We project that single-stranded based editing methodologies can be employed alongside preexisting genome engineering techniques to assist and expedite metabolic engineering and minimalized genome research.
ContributorsStandage-Beier, Kylie S (Author) / Wang, Xiao (Thesis director) / Haynes, Karmella (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2014-05
Description
The aim of this study was to explore cross-sectional and longitudinal aging differences in immediate and delayed visual and verbal memory abilities in individuals with Autism Spectrum Disorder (ASD) compared with neurotypicals (NTs). We measured hippocampal size, fornix fractional anisotropy (FA), and hippocampal and fornix freewater to understand how aging impacts memory structures. Longitudinal findings highlight vulnerabilities in immediate verbal memory and hippocampal volume, while cross-sectional findings indicate fornix freewater may increase at a faster rate in adults with ASD. Future research will examine cognitive and structural sex differences and will study how cognitive measures correlate with structural measures.
ContributorsSullivan, Georgia Rose (Author) / Braden, B. Blair (Thesis director) / Ofori, Edward (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
The aim of this study was to determine whether IUD administration, with and without the presence of Levo, and with and without the presence of the ovaries, impacts cognition in a rat model. Rats received either Sham or Ovariectomy (Ovx) surgery (removal of the ovaries), plus either no IUD, a Blank IUD (without Levo), or a Levo-releasing IUD (Levo IUD), enabling us to evaluate the effects of Ovx and the effects of IUD administration on cognition. Two weeks after surgery, all treatment groups were tested on the water radial arm maze, Morris water maze, and visible platform task to evaluate cognition. At sacrifice, upon investigation of the uteri, it was determined that some of the IUDs were no longer present in animals from these groups: Sham\u2014Blank IUD, Ovx\u2014Blank IUD, and Sham\u2014Levo IUD. Results from the remaining three groups showed that compared to Sham animals with no IUDs, Ovx animals with no IUDs had marginally impaired working memory performance, and that Ovx animals with Levo IUDs as compared to Ovx animals with no IUDs had marginally enhanced memory performance, not specific to a particular memory type. Results also showed that Ovx animals with Levo IUDs had qualitatively more cells in their vaginal smears and increased uterine horn weight compared to Ovx animals with no IUDs, suggesting local stimulation of the Levo IUDs to the uterine horns. Overall, these results provide alternative evidence to the hypothesis that the Levo IUD administers Levo in solely a localized manner, and suggests that the possibility for the Levo IUD to affect reproductive cyclicity in ovary-intact animals is not rejected. The potential for the Levo IUD to exert effects on cognition suggests that either the hormone does in fact systemically circulate, or that the Levo IUD administration affects cognition by altering an as yet undetermined hormonal or other feedback between the uterus and the brain.
ContributorsStrouse, Isabel Martha (Author) / Bimonte-Nelson, Heather (Thesis director) / Glenberg, Arthur (Committee member) / Sirianni, Rachael (Committee member) / Conrad, Cheryl (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
Description
Pinpoint control over endogenous gene expression in vivo has long been a fevered dream for clinicians and researchers alike. With the recent repurposing of programmable, RNA-guided DNA endonucleases from the CRISPR bacterial immune system, this dream is becoming a powerful reality. Engineered CRISPR based transcriptional regulators have enabled researchers to perturb endogenous gene expression in vivo, allowing for the therapeutic reprogramming of cell and tissue behavior. However, for this technology to be of maximal use, a variety of technological hurdles still need to be addressed. Here, we discuss recent advances and integrative strategies that can help pave the way towards a new class of transcriptional therapeutics.
ContributorsPandelakis, Matthew (Author) / Ebrahimkhani, Mohammad (Thesis director) / Kiani, Samira (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
The purpose of this project was to extend Whitehead 2016 to determine what neural substrates supported conflict-mediated learning. Unfortunately, as a result of the COVID-19 pandemic we were unable to address this. To repurpose the collected data, an analysis of which features of the Flanker task subjects were learning was conducted. Specifically, we wanted to know if subjects were learning by using the flanking stimuli to predict the central target or vice versa. Over 14 blocks comprised of 120 trials, we found that subjects made more stroop errors than flanker and target errors, indicating subjects were responding to stimuli in context of the flanker rather than the stroop effect.
ContributorsSobelman, Reanna Hayley (Author) / Blais, Chris (Thesis director) / Brewer, Gene (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-12
Description
One of the primary bottlenecks to chemical production in biological organisms is the toxicity of the chemical. Overexpression of efflux pumps has been shown to increase tolerance to aromatic compounds such as styrene and styrene oxide. Tight control of pump expression is necessary to maximize titers and prevent excessive strain on the cells. This study aimed to identify aromatic-sensitive native promoters and heterologous biosensors for construction of closed-loop control of efflux pump expression in E. coli. Using a promoter library constructed by Zaslaver et al., activation was measured through GFP output. Promoters were evaluated for their sensitivity to the addition of one of four aromatic compounds, their "leaking" of signal, and their induction threshold. Out of 43 targeted promoters, 4 promoters (cmr, mdtG, yahN, yajR) for styrene oxide, 2 promoters (mdtG, yahN) for styrene, 0 promoters for 2-phenylethanol, and 1 promoter for phenol (pheP) were identified as ideal control elements in aromatic bioproduction. In addition, a series of three biosensors (NahR, XylS, DmpR) known to be inducible by other aromatics were screened against styrene oxide, 2-phenylethanol, and phenol. The targeted application of these biosensors is aromatic-induced activation of linked efflux pumps. All three biosensors responded strongly in the presence of styrene oxide and 2-phenylethanol, with minor activation in the presence of phenol. Bioproduction of aromatics continues to gain traction in the biotechnology industry, and the continued discovery of aromatic-inducible elements will be essential to effective pathway control.
ContributorsXu, Jimmy (Author) / Nielsen, David (Thesis director) / Wang, Xuan (Committee member) / School of Life Sciences (Contributor) / Chemical Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Illness is one of the most unfortunate experiences that can occur during one's life. It often emerges without warning and when it is least expected. Illness is not only detrimental to the physical and emotional health of the person who is directly diagnosed, however. When one person is diagnosed with any kind of illness, many people are affected. Literature and art have always been used as vehicles to express their creators' thoughts and feelings. Those affected by illness sometimes adopt this method, using the art of storytelling to cope with and express their many emotions. Because there are so many affected people when even only one person is diagnosed, there are several different perspectives that are expressed and must be analyzed. This anthology, titled "Creativity, Medicine, and the Arts: An Anthology Edited and Annotated by Gabrielle Georgini," illustrates the correlation between various kinds of illnessesand literature. According to Merriam-Webster, illness is defined as "obsolete, an unhealthy condition of body or mind" (371). To make a patient healthy again, he must receive some kind oftreatment. Unfortunately, in some cases, a patient may not become healthy again even if they do receive treatment. Literature is an art, and art is a form of therapy. Therefore, patients can use literature and art as forms of treatment. Art and literature provide therapies for the mind. They can allow patients to relax and can work as a distraction from their illnesses. Art and literature can also be a form of expression. Those who are affected by illness can describe or depict their thoughts on paper, enabling them to clear their head or inform others about how they are feeling.
ContributorsGeorgini, Gabrielle Marie (Author) / Meloy, Elizabeth (Thesis director) / Vega, Sylvia (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05