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One of the largest problems facing modern medicine is drug resistance. Many classes of drugs can be rendered ineffective if their target is able to acquire beneficial mutations. While this is an excellent showcase of the power of evolution, it necessitates the development of increasingly stronger drugs to combat resistant

One of the largest problems facing modern medicine is drug resistance. Many classes of drugs can be rendered ineffective if their target is able to acquire beneficial mutations. While this is an excellent showcase of the power of evolution, it necessitates the development of increasingly stronger drugs to combat resistant pathogens. Not only is this strategy costly and time consuming, it is also unsustainable. To contend with this problem, many multi-drug treatment strategies are being explored. Previous studies have shown that resistance to some drug combinations is not possible, for example, resistance to a common antifungal drug, fluconazole, seems impossible in the presence of radicicol. We believe that in order to understand the viability of multi-drug strategies in combating drug resistance, we must understand the full spectrum of resistance mutations that an organism can develop, not just the most common ones. It is possible that rare mutations exist that are resistant to both drugs. Knowing the frequency of such mutations is important for making predictions about how problematic they will be when multi-drug strategies are used to treat human disease. This experiment aims to expand on previous research on the evolution of drug resistance in S. cerevisiae by using molecular barcodes to track ~100,000 evolving lineages simultaneously. The barcoded cells were evolved with serial transfers for seven weeks (200 generations) in three concentrations of the antifungal Fluconazole, three concentrations of the Hsp90 inhibitor Radicicol, and in four combinations of Fluconazole and Radicicol. Sequencing data was used to track barcode frequencies over the course of the evolution, allowing us to observe resistant lineages as they rise and quantify differences in resistance evolution across the different conditions. We were able to successfully observe over 100,000 replicates simultaneously, revealing many adaptive lineages in all conditions. Our results also show clear differences across drug concentrations and combinations, with the highest drug concentrations exhibiting distinct behaviors.

ContributorsApodaca, Samuel (Author) / Geiler-Samerotte, Kerry (Thesis director) / Schmidlin, Kara (Committee member) / Huijben, Silvie (Committee member) / School of Life Sciences (Contributor) / School of Molecular Sciences (Contributor) / School of Politics and Global Studies (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description

The majority of the public is not aware that common objects in their backyard can be mosquito breeding sites, thus leading to an increase in mosquitoes and mosquito-borne diseases affecting humans and animals during the peak seasons. An engaging app that instructs people of all ages how to identify, prevent,

The majority of the public is not aware that common objects in their backyard can be mosquito breeding sites, thus leading to an increase in mosquitoes and mosquito-borne diseases affecting humans and animals during the peak seasons. An engaging app that instructs people of all ages how to identify, prevent, and eliminate breeding sites may be of use in increasing positive behavioral changes in people, and therefore reducing available breeding sites for mosquitoes. The Embodied Games Lab in Psychology at Arizona State University created an educational game phone app using machine learning to teach students how to identify and eliminate mosquito breeding sites. Skeeter Breeder is an interactive, educational game that teaches participants about potential mosquito breeding sites and how to eliminate them from the immediate environment as documented by smartphone imagery. Currently, there is no educational game phone app that uses machine learning to teach this topic. This Thesis describes a pilot study focused on educating about common mosquito breeding sites and increasing the knowledge of 5th graders on the topic through an agentic (by taking their own pictures), engaging (game-like platform with rewards), and interactive (receiving immediate feedback on pictures) game developed from scratch at ASU.

ContributorsBharti, Aarushi (Author) / Johnson-Glenberg, Mina (Thesis director) / Huijben, Silvie (Committee member) / Barrett, The Honors College (Contributor) / Tech Entrepreneurship & Mgmt (Contributor) / Computing and Informatics Program (Contributor)
Created2023-05