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: Liebig, Jürgen
- Creators: Crook, Sharon
Description
At the heart of every eusocial insect colony is a reproductive division of labor. This division can emerge through dominance interactions at the adult stage or through the production of distinct queen and worker castes at the larval stage. In both cases, this division depends on plasticity within an individual to develop reproductive characteristics or serve as a worker. In order to gain insight into the evolution of reproductive plasticity in the social insects, I investigated caste determination and dominance in the ant Harpegnathos saltator, a species that retains a number of ancestral characteristics. Treatment of worker larvae with a juvenile hormone (JH) analog induced late-instar larvae to develop as queens. At the colony level, workers must have a mechanism to regulate larval development to prevent queens from developing out of season. I identified a new behavior in H. saltator where workers bite larvae to inhibit queen determination. Workers could identify larval caste based on a chemical signal specific to queen-destined larvae, and the production of this signal was directly linked to increased JH levels. This association provides a connection between the physiological factors that induce queen development and the production of a caste-specific larval signal. In addition to caste determination at the larval stage, adult workers of H. saltator compete to establish a reproductive hierarchy. Unlike other social insects, dominance in H. saltator was not related to differences in JH or ecdysteroid levels. Instead, changes in brain levels of biogenic amines, particularly dopamine, were correlated with dominance and reproductive status. Receptor genes for dopamine were expressed in both the brain and ovaries of H. saltator, and this suggests that dopamine may coordinate changes in behavior at the neurological level with ovarian status. Together, these studies build on our understanding of reproductive plasticity in social insects and provide insight into the evolution of a reproductive division of labor.
ContributorsPenick, Clint A (Author) / Liebig, Jürgen (Thesis advisor) / Brent, Colin (Committee member) / Gadau, Jürgen (Committee member) / Hölldobler, Bert (Committee member) / Rutowski, Ron (Committee member) / Arizona State University (Publisher)
Created2012
Description
The phycologist, M. R. Droop, studied vitamin B12 limitation in the flagellate Monochrysis lutheri and concluded that its specific growth rate depended on the concentration of the vitamin within the cell; i.e. the cell quota of the vitamin B12. The Droop model provides a mathematical expression to link growth rate to the intracellular concentration of a limiting nutrient. Although the Droop model has been an important modeling tool in ecology, it has only recently been applied to study cancer biology. Cancer cells live in an ecological setting, interacting and competing with normal and other cancerous cells for nutrients and space, and evolving and adapting to their environment. Here, the Droop equation is used to model three cancers.
First, prostate cancer is modeled, where androgen is considered the limiting nutrient since most tumors depend on androgen for proliferation and survival. The model's accuracy for predicting the biomarker for patients on intermittent androgen deprivation therapy is tested by comparing the simulation results to clinical data as well as to an existing simpler model. The results suggest that a simpler model may be more beneficial for a predictive use, although further research is needed in this field prior to implementing mathematical models as a predictive method in a clinical setting.
Next, two chronic myeloid leukemia models are compared that consider Imatinib treatment, a drug that inhibits the constitutively active tyrosine kinase BCR-ABL. Both models describe the competition of leukemic and normal cells, however the first model also describes intracellular dynamics by considering BCR-ABL as the limiting nutrient. Using clinical data, the differences in estimated parameters between the models and the capacity for each model to predict drug resistance are analyzed.
Last, a simple model is presented that considers ovarian tumor growth and tumor induced angiogenesis, subject to on and off anti-angiogenesis treatment. In this environment, the cell quota represents the intracellular concentration of necessary nutrients provided through blood supply. Mathematical analysis of the model is presented and model simulation results are compared to pre-clinical data. This simple model is able to fit both on- and off-treatment data using the same biologically relevant parameters.
First, prostate cancer is modeled, where androgen is considered the limiting nutrient since most tumors depend on androgen for proliferation and survival. The model's accuracy for predicting the biomarker for patients on intermittent androgen deprivation therapy is tested by comparing the simulation results to clinical data as well as to an existing simpler model. The results suggest that a simpler model may be more beneficial for a predictive use, although further research is needed in this field prior to implementing mathematical models as a predictive method in a clinical setting.
Next, two chronic myeloid leukemia models are compared that consider Imatinib treatment, a drug that inhibits the constitutively active tyrosine kinase BCR-ABL. Both models describe the competition of leukemic and normal cells, however the first model also describes intracellular dynamics by considering BCR-ABL as the limiting nutrient. Using clinical data, the differences in estimated parameters between the models and the capacity for each model to predict drug resistance are analyzed.
Last, a simple model is presented that considers ovarian tumor growth and tumor induced angiogenesis, subject to on and off anti-angiogenesis treatment. In this environment, the cell quota represents the intracellular concentration of necessary nutrients provided through blood supply. Mathematical analysis of the model is presented and model simulation results are compared to pre-clinical data. This simple model is able to fit both on- and off-treatment data using the same biologically relevant parameters.
ContributorsEverett, Rebecca Anne (Author) / Kuang, Yang (Thesis advisor) / Nagy, John (Committee member) / Milner, Fabio (Committee member) / Crook, Sharon (Committee member) / Jackiewicz, Zdzislaw (Committee member) / Arizona State University (Publisher)
Created2015
Description
Social insect colonies exhibit striking diversity in social organization. Included in this overwhelming variation in structure are differences in colony queen number. The number of queens per colony varies both intra- and interspecifically and has major impacts on the social dynamics of a colony and the fitness of its members. To understand the evolutionary transition from single to multi-queen colonies, I examined a species which exhibits variation both in mode of colony founding and in the queen number of mature colonies. The California harvester ant Pogonomyrmex californicus exhibits both variation in the number of queens that begin a colony (metrosis) and in the number of queens in adult colonies (gyny). Throughout most of its range, colonies begin with one queen (haplometrosis) but in some populations multiple queens cooperate to initiate colonies (pleometrosis). I present results that confirm co-foundresses are unrelated. I also map the geographic occurrence of pleometrotic populations and show that the phenomenon appears to be localized in southern California and Northern Baja California. Additionally, I provide genetic evidence that pleometrosis leads to primary polygyny (polygyny developing from pleometrosis) a phenomenon which has received little attention and is poorly understood. Phylogenetic and haplotype analyses utilizing mitochondrial markers reveal that populations of both behavioral types in California are closely related and have low mitochondrial diversity. Nuclear markers however, indicate strong barriers to gene flow between focal populations. I also show that intrinsic differences in queen behavior lead to the two types of populations observed. Even though populations exhibit strong tendencies on average toward haplo- or pleometrosis, within population variation exists among queens for behaviors relevant to metrosis and gyny. These results are important in understanding the dynamics and evolutionary history of a distinct form of cooperation among unrelated social insects. They also help to understand the dynamics of intraspecific variation and the conflicting forces of local adaptation and gene flow.
ContributorsOverson, Rick P (Author) / Gadau, Jürgen (Thesis advisor) / Fewell, Jennifer H (Committee member) / Hölldobler, Bert (Committee member) / Johnson, Robert A. (Committee member) / Liebig, Jürgen (Committee member) / Arizona State University (Publisher)
Created2011
Description
Predicting resistant prostate cancer is critical for lowering medical costs and improving the quality of life of advanced prostate cancer patients. I formulate, compare, and analyze two mathematical models that aim to forecast future levels of prostate-specific antigen (PSA). I accomplish these tasks by employing clinical data of locally advanced prostate cancer patients undergoing androgen deprivation therapy (ADT). I demonstrate that the inverse problem of parameter estimation might be too complicated and simply relying on data fitting can give incorrect conclusions, since there is a large error in parameter values estimated and parameters might be unidentifiable. I provide confidence intervals to give estimate forecasts using data assimilation via an ensemble Kalman Filter. Using the ensemble Kalman Filter, I perform dual estimation of parameters and state variables to test the prediction accuracy of the models. Finally, I present a novel model with time delay and a delay-dependent parameter. I provide a geometric stability result to study the behavior of this model and show that the inclusion of time delay may improve the accuracy of predictions. Also, I demonstrate with clinical data that the inclusion of the delay-dependent parameter facilitates the identification and estimation of parameters.
ContributorsBaez, Javier (Author) / Kuang, Yang (Thesis advisor) / Kostelich, Eric (Committee member) / Crook, Sharon (Committee member) / Gardner, Carl (Committee member) / Nagy, John (Committee member) / Arizona State University (Publisher)
Created2017
Description
The most abundantly studied societies, with the exception of humans, are those of the eusocial insects, which include all ants. Eusocial insect societies are typically composed of many dozens to millions of individuals, referred to as nestmates, which require some form of communication to maintain colony cohesion and coordinate the activities within them. Nestmate recognition is the process of distinguishing between nestmates and non-nestmates, and embodies the first line of defense for social insect colonies. In ants, nestmate recognition is widely thought to occur through olfactory cues found on the exterior surfaces of individuals. These cues, called cuticular hydrocarbons (CHCs), comprise the overwhelming majority of ant nestmate profiles and help maintain colony identity. In this dissertation, I investigate how nestmate recognition is influenced by evolutionary, ontogenetic, and environmental factors. First, I contributed to the sequencing and description of three ant genomes including the red harvester ant, Pogonomyrmex barbatus, presented in detail here. Next, I studied how variation in nestmate cues may be shaped through evolution by comparatively studying a family of genes involved in fatty acid and hydrocarbon biosynthesis, i.e., the acyl-CoA desaturases, across seven ant species in comparison with other social and solitary insects. Then, I tested how genetic, developmental, and social factors influence CHC profile variation in P. barbatus, through a three-part study. (1) I conducted a descriptive, correlative study of desaturase gene expression and CHC variation in P. barbatus workers and queens; (2) I explored how larger-scale genetic variation in the P. barbatus species complex influences CHC variation across two genetically isolated lineages (J1/J2 genetic caste determining lineages); and (3) I experimentally examined how CHC development is influenced by an individual’s social environment. In the final part of my work, I resolved discrepancies between previous findings of nestmate recognition behavior in P. barbatus by studying how factors of territorial experience, i.e., spatiotemporal relationships, affect aggressive behaviors among red harvester ant colonies. Through this research, I was able to identify promising methodological approaches and candidate genes, which both broadens our understanding of P. barbatus nestmate recognition systems and supports future functional genetic studies of CHCs in ants.
ContributorsCash, Elizabeth I (Author) / Gadau, Jürgen (Thesis advisor) / Liebig, Jürgen (Thesis advisor) / Fewell, Jennifer (Committee member) / Hölldobler, Berthold (Committee member) / Kusumi, Kenro (Committee member) / Arizona State University (Publisher)
Created2016
Description
Dominance behavior can regulate a division of labor in a group, such as that between reproductive and non-reproductive individuals. Manipulations of insect societies in a controlled environment can reveal how dominance behavior is regulated. Here, I examined how morphological caste, fecundity, group size, and age influence the expression of dominance behavior using the ponerine ant Harpegnathos saltator. All H. saltator females have the ability to reproduce. Only those with a queen morphology that enables dispersal, however, show putative sex pheromones. In contrast, those with a worker morphology normally express dominance behavior. To evaluate how worker-like dominance behavior and associated traits could be expressed in queens, I removed the wings from alate gynes, those with a queen morphology who had not yet mated or left the nest, making them dealate. Compared to gynes with attached wings, dealates frequently performed dominance behavior. In addition, only the dealates demonstrated worker-like ovarian activity in the presence of reproductive individuals, whereas gynes with wings produced sex pheromones exclusively. Therefore, the attachment of wings determines a gyne’s expression of worker-like dominance behavior and physiology. When the queen dies, workers establish a reproductive hierarchy among themselves by performing a combination of dominance behaviors. To understand how reproductive status depends on these interactions as well as a worker’s age, I measured the frequency of dominance behaviors in groups of different size composed of young and old workers. The number of workers who expressed dominance scaled with the size of the group, but younger ones were more likely to express dominance behavior and eventually become reproductive. Therefore, the predisposition of age integrates with a self-organized process to form this reproductive hierarchy. A social insect’s fecundity and fertility signal depends on social context because fecundity increases with colony size. To evaluate how a socially dependent signal regulates dominance behavior, I manipulated a reproductive worker’s social context. Reproductive workers with reduced fecundity and a less prominent fertility signal expressed more dominance behavior than those with a stronger fertility signal and higher fecundity. Therefore, dominance behavior reinforces rank to compensate for a weak signal, indicating how social context can feed back to influence the maintenance of dominance. Mechanisms that regulate H. saltator’s reproductive hierarchy can inform how the reproductive division of labor is regulated in other groups of animals.
ContributorsPyenson, Benjamin (Author) / Liebig, Jürgen (Thesis advisor) / Hölldobler, Bert (Committee member) / Fewell, Jennifer (Committee member) / Pratt, Stephen (Committee member) / Kang, Yun (Committee member) / Arizona State University (Publisher)
Created2022
Description
Ant colonies provide numerous opportunities to study communication systems that maintain the cohesion of eusocial groups. In many ant species, workers have retained their ovaries and the ability to produce male offspring; however, they generally refrain from producing their own sons when a fertile queen is present in the colony. Although mechanisms that facilitate the communication of the presence of a fertile queen to all members of the colony have been highly studied, those studies have often overlooked the added challenge faced by polydomous species, which divide their nests across as many as one hundred satellite nests resulting in workers potentially having infrequent contact with the queen. In these polydomous contexts, regulatory phenotypes must extend beyond the immediate spatial influence of the queen.
This work investigates mechanisms that can extend the spatial reach of fertility signaling and reproductive regulation in three polydomous ant species. In Novomessor cockerelli, the presence of larvae but not eggs is shown to inhibit worker reproduction. Then, in Camponotus floridanus, 3-methylheptacosane found on the queen cuticle and queen-laid eggs is verified as a releaser pheromone sufficient to disrupt normally occurring aggressive behavior toward foreign workers. Finally, the volatile and cuticular hydrocarbon pheromones present on the cuticle of Oecophylla smaragdina queens are shown to release strong attraction response by workers; when coupled with previous work, this result suggests that these chemicals may underly both the formation of a worker retinue around the queen as well as egg-located mechanisms of reproductive regulation in distant satellite nests. Whereas most previous studies have focused on the short-range role of hydrocarbons on the cuticle of the queen, these studies demonstrate that eusocial insects may employ longer range regulatory mechanisms. Both queen volatiles and distributed brood can extend the range of queen fertility signaling, and the use of larvae for fertility signaling suggest that feeding itself may be a non-chemical mechanism for reproductive regulation. Although trail laying in mass-recruiting ants is often used as an example of complex communication, reproductive regulation in ants may be a similarly complex example of insect communication, especially in the case of large, polydomous ant colonies.
This work investigates mechanisms that can extend the spatial reach of fertility signaling and reproductive regulation in three polydomous ant species. In Novomessor cockerelli, the presence of larvae but not eggs is shown to inhibit worker reproduction. Then, in Camponotus floridanus, 3-methylheptacosane found on the queen cuticle and queen-laid eggs is verified as a releaser pheromone sufficient to disrupt normally occurring aggressive behavior toward foreign workers. Finally, the volatile and cuticular hydrocarbon pheromones present on the cuticle of Oecophylla smaragdina queens are shown to release strong attraction response by workers; when coupled with previous work, this result suggests that these chemicals may underly both the formation of a worker retinue around the queen as well as egg-located mechanisms of reproductive regulation in distant satellite nests. Whereas most previous studies have focused on the short-range role of hydrocarbons on the cuticle of the queen, these studies demonstrate that eusocial insects may employ longer range regulatory mechanisms. Both queen volatiles and distributed brood can extend the range of queen fertility signaling, and the use of larvae for fertility signaling suggest that feeding itself may be a non-chemical mechanism for reproductive regulation. Although trail laying in mass-recruiting ants is often used as an example of complex communication, reproductive regulation in ants may be a similarly complex example of insect communication, especially in the case of large, polydomous ant colonies.
ContributorsEbie, Jessica (Author) / Liebig, Jürgen (Thesis advisor) / Hölldobler, Bert (Thesis advisor) / Pratt, Stephen (Committee member) / Smith, Brian (Committee member) / Rutowski, Ronald (Committee member) / Arizona State University (Publisher)
Created2020
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 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