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Construction of Synthetic Microbial Consortia for Modeling Ecological Systems

Description

Ecology has been an actively studied topic recently, along with the rapid development of human microbiota-based technology. Scientists have made remarkable progress using bioinformatics tools to identify species and analyze composition. However, a thorough understanding of interspecies interactions of microbial ecosystems is still lacking, which has been a significant obstacle…

Ecology has been an actively studied topic recently, along with the rapid development of human microbiota-based technology. Scientists have made remarkable progress using bioinformatics tools to identify species and analyze composition. However, a thorough understanding of interspecies interactions of microbial ecosystems is still lacking, which has been a significant obstacle in the further development of related technologies. In this work, a genetic circuit design principle with synthetic biology approaches is developed to form two-strain microbial consortia with different inter-strain interactions. The microbial systems are well-defined and inducible. Co-culture experiment results show that our microbial consortia behave consistently with previous ecological knowledge and thus serves as excellent model systems to simulate ecosystems with similar interactions. Colony patterns also emerge when co-culturing multiple species on solid media. With the engineered microbial consortia, image-processing based methods were developed to quantify the shape of co-culture colonies and distinguish microbial consortia with different interactions. Factors that affect the population ratios were identified through induction and variations in the inoculation process. Further time-lapse experiments revealed the basic rules of colony growth, composition variation, patterning, and how spatial factors impact the co-culture colony.

ContributorsChen, Xingwen (Author) / Wang, Xiao (Thesis advisor) / Kuang, Yang (Committee member) / Tian, Xiaojun (Committee member) / Brafman, David (Committee member) / Plaisier, Christopher (Committee member) / Arizona State University (Publisher)

Created2022

Emergent Dynamics Arising from the Feedback Between Synthetic Gene Circuit and Host Cell Growth

Description

The mutual inhibition between synthetic gene circuits and cell growth produces growth feedback in the host-circuit system. Previous studies have demonstrated that the growth feedback has an marked impact on the molecular dynamics of the host-circuit system. However, the complexity of the growth feedback effect is not fully understood. A…

The mutual inhibition between synthetic gene circuits and cell growth produces growth feedback in the host-circuit system. Previous studies have demonstrated that the growth feedback has an marked impact on the molecular dynamics of the host-circuit system. However, the complexity of the growth feedback effect is not fully understood. A theoretical framework was developed to study the dynamics of the coupling between growth feedback and synthetic gene circuits. The study’s results reveal three major points about the impact of growth feedback. First, a nonlinear emergent behavior mediated by growth feedback. The unexpected behavior depends on the dynamic ribosome allocation between gene circuit expression and host cell growth. Second, the emergence and loss of unexpected qualitative states on the host-circuit system generated by ultrasensitive growth feedback. Third, the growth feedback-induced cooperativity behavior in synthetic gene modules competing for resources. In addition, growth feedback attenuated the winner-takes-all rules on resource competition between the two self-activating modules. These results demonstrate that growth feedback plays an important role in the host-circuit system’s molecular dynamics. Characterizing general principles from the effect of growth facilitates the ability to minimize or even harness unexpected gene expression behaviors derived from the effect of growth feedback.

ContributorsMelendez-Alvarez, Juan Ramon (Author) / Tian, Xiaojun (Thesis advisor) / Wang, Xiao (Committee member) / Kuang, Yang (Committee member) / Arizona State University (Publisher)

Created2022

Characterization of Low Fluid Shear Modeled Microgravity Culture on the Stress Response of Burkholderia cepacia complex

Description

One of the identified health risk areas for human spaceflight is infectious disease, particularly involving environmental microorganisms already found on the International Space Station (ISS). In particular, bacteria belonging to the Burkholderia cepacia complex (Bcc) which can cause human disease in those who are immunocompromised, have been identified in the…

One of the identified health risk areas for human spaceflight is infectious disease, particularly involving environmental microorganisms already found on the International Space Station (ISS). In particular, bacteria belonging to the Burkholderia cepacia complex (Bcc) which can cause human disease in those who are immunocompromised, have been identified in the ISS water supply. This present study characterized the effect of spaceflight analog culture conditions on Bcc to certain physiological stresses (acid and thermal as well as intracellular survival in U927 human macrophage cells). The NASA-designed Rotating Wall Vessel (RWV) bioreactor was used as the spaceflight analogue culture system in these studies to grow Bcc bacterial cells under Low Shear Modeled Microgravity (LSMMG) conditions. Results show that LSMMG culture increased the resistance of Bcc to both acid and thermal stressors, but did not alter phagocytic uptake in 2-D monolayers of human monocytes.

ContributorsVu, Christian-Alexander (Author) / Nickerson, Cheryl (Thesis director) / Barrila, Jennifer (Committee member) / Ott, Mark (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)

Created2023-05

Prostate Cancer Modeling: Exploring a Path from Theory and Practice

Description

The representation of a patient’s characteristics as the parameters of a model is a key component in many studies of personalized medicine, where the underlying mathematical models are used to describe, explain, and forecast the course of treatment. In this context, clinical observations form the bridge between the mathematical frameworks…

The representation of a patient’s characteristics as the parameters of a model is a key component in many studies of personalized medicine, where the underlying mathematical models are used to describe, explain, and forecast the course of treatment. In this context, clinical observations form the bridge between the mathematical frameworks and applications. However, the formulation and theoretical studies of the models and the clinical studies are often not completely compatible, which is one of the main obstacles in the application of mathematical models in practice. The goal of my study is to extend a mathematical framework to model prostate cancer based mainly on the concept of cell-quota within an evolutionary framework and to study the relevant aspects for the model to gain useful insights in practice. Specifically, the first aim is to construct a mathematical model that can explain and predict the observed clinical data under various treatment combinations. The second aim is to find a fundamental model structure that can capture the dynamics of cancer progression within a realistic set of data. Finally, relevant clinical aspects such as how the patient's parameters change over the course of treatment and how to incorporate treatment optimization within a framework of uncertainty quantification, will be examined to construct a useful framework in practice.

ContributorsPhan, Tin (Author) / Kuang, Yang (Thesis advisor) / Kostelich, Eric J (Committee member) / Crook, Sharon (Committee member) / Maley, Carlo (Committee member) / Bryce, Alan (Committee member) / Arizona State University (Publisher)

Created2021

Spatial Temporal Patterning and Dynamics of E. Coli Growth with Nutrient Variation

Description

Synthetic biology (SB) has become an important field of science focusing on designing and engineering new biological parts and systems, or re-designing existing biological systems for useful purposes. The dramatic growth of SB throughout the past two decades has not only provided us numerous achievements, but also brought us more…

Synthetic biology (SB) has become an important field of science focusing on designing and engineering new biological parts and systems, or re-designing existing biological systems for useful purposes. The dramatic growth of SB throughout the past two decades has not only provided us numerous achievements, but also brought us more timely and underexplored problems. In SB's entire history, mathematical modeling has always been an indispensable approach to predict the experimental outcomes, improve experimental design and obtain mechanism-understanding of the biological systems. \textit{Escherichia coli} (\textit{E. coli}) is one of the most important experimental platforms, its growth dynamics is the major research objective in this dissertation. Chapter 2 employs a reaction-diffusion model to predict the \textit{E. coli} colony growth on a semi-solid agar plate under multiple controls. In that chapter, a density-dependent diffusion model with non-monotonic growth to capture the colony's non-linear growth profile is introduced. Findings of the new model to experimental data are compared and contrasted with those from other proposed models. In addition, the cross-sectional profile of the colony are computed and compared with experimental data. \textit{E. coli} colony is also used to perform spatial patterns driven by designed gene circuits. In Chapter 3, a gene circuit (MINPAC) and its corresponding pattern formation results are presented. Specifically, a series of partial differential equation (PDE) models are developed to describe the pattern formation driven by the MINPAC circuit. Model simulations of the patterns based on different experimental conditions and numerical analysis of the models to obtain a deeper understanding of the mechanisms are performed and discussed. Mathematical analysis of the simplified models, including traveling wave analysis and local stability analysis, is also presented and used to explore the control strategies of the pattern formation. The interaction between the gene circuit and the host \textit{E. coli} may be crucial and even greatly affect the experimental outcomes. Chapter 4 focuses on the growth feedback between the circuit and the host cell under different nutrient conditions. Two ordinary differential equation (ODE) models are developed to describe such feedback with nutrient variation. Preliminary results on data fitting using both two models and the model dynamical analysis are included.

ContributorsHe, Changhan (Author) / Kuang, Yang (Thesis advisor) / Wang, Xiao (Committee member) / Kostelich, Eric (Committee member) / Tian, Xiaojun (Committee member) / Gumel, Abba (Committee member) / Arizona State University (Publisher)

Created2021

Cognitive Aging and Flexibility in Canids

Description

This dissertation describes a series of four studies on cognitive aging, working memory, and cognitive flexibility in dogs (Canis lupus familiaris) and their wild relatives. In Chapters 2 and 3, I designed assessments for age-related cognitive deficits in pet dogs which can be deployed rapidly using inexpensive and accessible materials.…

This dissertation describes a series of four studies on cognitive aging, working memory, and cognitive flexibility in dogs (Canis lupus familiaris) and their wild relatives. In Chapters 2 and 3, I designed assessments for age-related cognitive deficits in pet dogs which can be deployed rapidly using inexpensive and accessible materials. These novel tests can be easily implemented by owners, veterinarians, and clinicians and therefore, may improve care for elderly dogs by aiding in the diagnosis of dementia. In addition, these widely deployable tests may facilitate the use of dementia in pet dogs as a naturally occurring model of Alzheimer’s Disease in humans.In Chapters 4 and 5, I modified one of these tests to demonstrate for the first time that coyotes (Canis latrans) and wolves (Canis lupus lupus) develop age-related deficits in cognitive flexibility. This was an important first step towards differentiating between the genetic and environmental components of dementia in dogs and in turn, humans. Unexpectedly, I also detected cognitive deficits in young, adult dogs and wolves but not coyotes. These finding add to a recent shift in understanding cognitive development in dogs which may improve cognitive aging tests as well as training, care, and use of working and pet dogs. These findings also suggest that the ecology of coyotes may select for flexibility earlier in development. In Chapter 5, I piloted the use of the same cognitive flexibility test for red and gray foxes so that future studies may test for lifespan changes in the cognition of small-bodied captive canids. More broadly, this paradigm may accommodate physical and behavioral differences between diverse pet and captive animals. In Chapters 4 and 5, I examined which ecological traits drive the evolution of behavioral flexibility and in turn, species resilience. I found that wolves displayed less flexibility than dogs and coyotes suggesting that species which do not rely heavily on unstable resources may be ill-equipped to cope with human habitat modification. Ultimately, this comparative work may help conservation practitioners to identify and protect species that cannot cope with rapid and unnatural environmental change.

ContributorsVan Bourg, Joshua (Author) / Wynne, Clive D (Thesis advisor) / Aktipis, C. Athena (Committee member) / Gilby, Ian C (Committee member) / Young, Julie K (Committee member) / Arizona State University (Publisher)

Created2022

Cropland Carbon Sequestration in Arizona: Assessing the Impact of Agricultural Land Use on Aboveground Carbon Storage

Description

Since the 20th century, Arizona has undergone shifts in agricultural practices, driven by urban expansion and crop irrigation regulations. These changes present environmental challenges, altering atmospheric processes and influencing climate dynamics. Given the potential threats of climate change and drought on water availability for agriculture, further modifications in the agricultural…

Since the 20th century, Arizona has undergone shifts in agricultural practices, driven by urban expansion and crop irrigation regulations. These changes present environmental challenges, altering atmospheric processes and influencing climate dynamics. Given the potential threats of climate change and drought on water availability for agriculture, further modifications in the agricultural landscape are expected. To understand these land use changes and their impact on carbon dynamics, our study quantified aboveground carbon storage in both cultivated and abandoned agricultural fields. To accomplish this, we employed Python and various geospatial libraries in Jupyter Notebook files, for thorough dataset assembly and visual, quantitative analysis. We focused on nine counties known for high cultivation levels, primarily located in the lower latitudes of Arizona. Our analysis investigated carbon dynamics across not only abandoned and actively cultivated croplands but also neighboring uncultivated land, for which we estimated the extent. Additionally, we compared these trends with those observed in developed land areas. The findings revealed a hierarchy in aboveground carbon storage, with currently cultivated lands having the lowest levels, followed by abandoned croplands and uncultivated wilderness. However, wilderness areas exhibited significant variation in carbon storage by county compared to cultivated and abandoned lands. Developed lands ranked highest in aboveground carbon storage, with the median value being the highest. Despite county-wide variations, abandoned croplands generally contained more carbon than currently cultivated areas, with adjacent wilderness lands containing even more than both. This trend suggests that cultivating croplands in the region reduces aboveground carbon stores, while abandonment allows for some replenishment, though only to a limited extent. Enhancing carbon stores in Arizona can be achieved through active restoration efforts on abandoned cropland. By promoting native plant regeneration and boosting aboveground carbon levels, these measures are crucial for improving carbon sequestration. We strongly advocate for implementing this step to facilitate the regrowth of native plants and enhance overall carbon storage in the region.

ContributorsGoodwin, Emily (Author) / Eikenberry, Steffen (Thesis director) / Kuang, Yang (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor)

Created2024-05

Analyzing Parameter Impact in Computational Modeling of Glioblastoma Multiforme Growth

Description

Glioblastoma Multiforme is a prevalent and aggressive brain tumor. It has an average 5-year survival rate of 6% and average survival time of 14 months. Using patient-specific MRI data from the Barrow Neurological Institute, this thesis investigates the impact of parameter manipulation on reaction-diffusion models for predicting and simulating glioblastoma…

Glioblastoma Multiforme is a prevalent and aggressive brain tumor. It has an average 5-year survival rate of 6% and average survival time of 14 months. Using patient-specific MRI data from the Barrow Neurological Institute, this thesis investigates the impact of parameter manipulation on reaction-diffusion models for predicting and simulating glioblastoma growth. The study aims to explore key factors influencing tumor morphology and to contribute to enhancing prediction techniques for treatment.

ContributorsShayegan, Tara (Author) / Kostelich, Eric (Thesis director) / Kuang, Yang (Committee member) / Barrett, The Honors College (Contributor) / School of Human Evolution & Social Change (Contributor)

Created2024-05

Guía para planificar acciones contra el calor para los vecindarios de la zona metropolitana de Phoenix: crear soluciones al calor urbano en el Valle del Sol

Description

En la zona metropolitana de Phoenix, el calor urbano está afectando la salud, la seguridad y la economía y se espera que estos impactos empeoren con el tiempo. Se prevé que el número de días por encima de 110˚F aumentará más del doble para el 2060. En mayo de 2017,…

En la zona metropolitana de Phoenix, el calor urbano está afectando la salud, la seguridad y la economía y se espera que estos impactos empeoren con el tiempo. Se prevé que el número de días por encima de 110˚F aumentará más del doble para el 2060. En mayo de 2017, The Nature Conservancy, el Departamento de Salud Pública del condado de Maricopa, Central Arizona Conservation Alliance, la Red de Investigación en Sostenibilidad sobre la Resiliencia Urbana a Eventos Extremos, el Centro de Investigación del Clima Urbano de Arizona State University y el Center for Whole Communities lanzaron un proceso participativo de planificación de acciones contra el calor para identificar tanto estrategias de mitigación como de adaptación a fin de reducir directamente el calor y mejorar la capacidad de los residentes para lidiar con el calor. Las organizaciones comunitarias con relaciones existentes en tres vecindarios seleccionados para la planificación de acciones contra el calor se unieron más tarde al equipo del proyecto: Phoenix Revitalization Corporation, RAILMesa y Puente Movement. Más allá de construir un plan de acción comunitario contra el calor y completar proyectos de demostración, este proceso participativo fue diseñado para desarrollar conciencia, iniciativa y cohesión social en las comunidades subrepresentadas. Asimismo el proceso de planificación de acciones contra el calor fue diseñado para servir como modelo para esfuerzos futuros de resiliencia al calor y crear una visión local, contextual y culturalmente apropiada de un futuro más seguro y saludable. El método iterativo de planificación y participación utilizado por el equipo del proyecto fortaleció las relaciones dentro y entre los vecindarios, las organizaciones comunitarias, los responsables de la toma de decisiones y el equipo núcleo, y combinó la sabiduría de la narración de historias y la evidencia científica para comprender mejor los desafíos actuales y futuros que enfrentan los residentes durante eventos de calor extremo. Como resultado de tres talleres en cada comunidad, los residentes presentaron ideas que quieren ver implementadas para aumentar su comodidad y seguridad térmica durante los días de calor extremo.

Como se muestra a continuación, las ideas de los residentes se interceptaron en torno a conceptos similares, pero las soluciones específicas variaron entre los vecindarios. Por ejemplo, a todos los vecindarios les gustaría agregar sombra a sus corredores peatonales, pero variaron las preferencias para la ubicación de las mejoras para dar sombra. Algunos vecindarios priorizaron las rutas de transporte público, otros priorizaron las rutas utilizadas por los niños en su camino a la escuela y otros quieren paradas de descanso con sombra en lugares clave. Surgieron cuatro temas estratégicos generales en los tres vecindarios: promover y educar; mejorar la comodidad/capacidad de afrontamiento; mejorar la seguridad; fortalecer la capacidad. Estos temas señalan que existen serios desafíos de seguridad contra el calor en la vida diaria de los residentes y que la comunidad, los negocios y los sectores responsables de la toma de decisión deben abordar esos desafíos.

Los elementos del plan de acción contra el calor están diseñados para incorporarse a otros esfuerzos para aliviar el calor, crear ciudades resilientes al clima y brindar salud y seguridad pública. Los socios de implementación del plan de acción contra el calor provienen de la región de la zona metropolitana de Phoenix, y se brindan recomendaciones para apoyar la transformación a una ciudad más fresca.

Para ampliar la escala de este enfoque, los miembros del equipo del proyecto recomiendan a) compromiso continuo e inversiones en estos vecindarios para implementar el cambio señalado como vital por los residentes, b) repetir el proceso de planificación de acción contra el calor con líderes comunitarios en otros vecindarios, y c) trabajar con las ciudades, los planificadores urbanos y otras partes interesadas para institucionalizar este proceso, apoyando las políticas y el uso de las métricas propuestas para crear comunidades más frescas.

ContributorsMesserschmidt, Maggie (Contributor) / Guardaro, Melissa (Contributor) / White, Jessica R. (Contributor) / Berisha, Vjollca (Contributor) / Hondula, David M. (Contributor) / Feagan, Mathieu (Contributor) / Grimm, Nancy (Contributor) / Beule, Stacie (Contributor) / Perea, Masavi (Contributor) / Ramirez, Maricruz (Contributor) / Olivas, Eva (Contributor) / Bueno, Jessica (Contributor) / Crummey, David (Contributor) / Winkle, Ryan (Contributor) / Rothballer, Kristin (Contributor) / Mocine-McQueen, Julian (Contributor) / Maurer, Maria (Artist) / Coseo, Paul (Artist) / Crank, Peter J (Designer) / Broadbent, Ashley (Designer) / McCauley, Lisa (Designer) / Nature's Cooling Systems Project (Contributor) / Nature Conservancy (U.S.) (Contributor) / Phoenix Revitalization Corporation (Contributor) / Puente Movement (Contributor) / Maricopa County (Ariz.). Department of Public Health (Contributor) / Central Arizona Conservation Alliance (Contributor) / Arizona State University. Urban Climate Research Center (Contributor) / Arizona State University. Urban Resilience to Extremes Sustainability Research Network (Contributor) / Center for Whole Communities (Contributor) / RAILmesa (Contributor) / Vitalyst Health Foundation (Funder)

Created2022

Heat Mitigation Solutions Guide for Mobile Homes

Description

According to the Centers for Disease Control and Prevention (CDC), more people die in the U.S. from heat than from all other natural disasters combined. According to the Environmental Protection Agency (EPA), more than 1,300 deaths per year in the United States are due to extreme heat. Arizona, California and…

According to the Centers for Disease Control and Prevention (CDC), more people die in the U.S. from heat than from all other natural disasters combined. According to the Environmental Protection Agency (EPA), more than 1,300 deaths per year in the United States are due to extreme heat. Arizona, California and Texas are the three states with the highest burden, accounting for 43% of all heat-related deaths according to the CDC.

Although only 5% of housing in Maricopa County, Arizona, is mobile homes, approximately 30% of indoor heat-related deaths occur in these homes. Thus, the residents of mobile homes in Maricopa County are disproportionately affected by heat. Mobile home residents are extremely exposed to heat due to the high density of mobile home parks, poor construction of dwellings, lack of vegetation, socio-demographic features and not being eligible to get utility and financial assistance.

We researched numerous solutions across different domains that could help build the heat resilience of mobile home residents. As a result we found 50 different solutions for diverse stakeholders, budgets and available resources. The goal of this toolbox is to present these solutions and to explain how to apply them in order to get the most optimal result and build About this Solutions Guide People who live in mobile homes are 6 to 8 times more likely to die of heat-associated deaths. heat resilience for mobile home residents. These solutions were designed as a coordinated set of actions for everyone — individual households, mobile home residents, mobile home park owners, cities and counties, private businesses and nonprofits serving mobile home parks, and other stakeholders — to be able to contribute to heat mitigation for mobile home residents.

When we invest in a collective, coordinated suite of solutions that are designed specifically to address the heat vulnerability of mobile homes residents, we can realize a resilience dividend in maintaining affordable, feasible, liveable housing for the 20 million Americans who choose mobile homes and manufactured housing as their place to live and thrive.

ContributorsVarfalameyeva, Katsiaryna (Author) / Solís, Patricia (Author) / Phillips, Lora A. (Author) / Charley, Elisha (Author) / Hondula, David M. (Author) / Kear, Mark (Author)

Created2021