\begin{abstract}The human immunodeficiency virus (HIV) pandemic, which causes the syndrome of opportunistic infections that characterize the late stage HIV disease, known as the acquired immunodeficiency syndrome (AIDS), remains a major public health challenge to many parts of the world. This dissertation contributes in providing deeper qualitative insights into the transmission dynamics and control of the HIV/AIDS disease in Men who have Sex with Men (MSM) community. A new mathematical model (which is relatively basic), which incorporates some of the pertinent aspects of HIV epidemiology and immunology and fitted using the yearly new case data of the MSM population from the State of Arizona, was designed and used to assess the population-level impact of awareness of HIV infection status and condom-based intervention, on the transmission dynamics and control of HIV/AIDS in an MSM community. Conditions for the existence and asymptotic stability of the various equilibria ofthe model were derived. The numerical simulations showed that the prospects for the effective control and/or elimination of HIV/AIDS in the MSM community in the United States are very promising using a condom-based intervention, provided the condom efficacy is high and the compliance is moderate enough. The model was extended in Chapter 3 to account for the effect of risk-structure, staged-progression property of HIV disease, and the use of pre-exposure prophylaxis (PrEP) on the spread and control of the disease. The model was shown to undergo a PrEP-induced \textit{backward bifurcation} when the associated control reproduction number is less than one. It was shown that when the compliance in PrEP usage is $50%(80%)$ then about $19.1%(34.2%)$ of the yearly new HIV/AIDS cases recorded at the peak will have been prevented, in comparison to the worst-case scenario where PrEP-based intervention is not implemented in the MSM community. It was also shown that the HIV pandemic elimination is possible from the MSM community even for the scenario when the effective contact rate is increased by 5-fold from its baseline value, if low-risk individuals take at least 15 years before they change their risky behavior and transition to the high-risk group (regardless of the value of the transition rate from high-risk to low-risk susceptible population).

The Kingdom of Saudi Arabia (KSA), which hosts some of the largest mass gatherings of humans globally every year, has seen the emergence of two coronavirus pandemics, namely the 2012 middle eastern respiratory syndrome (MERS-CoV) and the 2019 SARS-CoV-2 pandemics. This dissertation contributes in providing deeper insight into the transmission dynamics and control of the two diseases in the Kingdom. A model for SARS-CoV-2 transmission dynamics, which incorporates the key features of the disease, was designed first of all. Its disease-free equilibrium was shown, using Lyapunov function theory, to be globally-asymptotically stable when the associated reproduction number is less than one. The model, which has a unique and locally-asymptotically stable endemic equilibrium (for a special case) when the reproduction threshold exceeds one, was fitted using observed data for the KSA. Global sensitivity analysis was carried out to identify the key parameters of the model that have the most influence on the disease burden in the Kingdom. The model was used to assess the population-level impacts of control and mitigation interventions. It was shown that a face mask use strategy, based on using masks of moderate to high efficacy, can lead to the elimination of the pandemic if the coverage in its usage is high enough. A model for the spread of MERS-CoV in the human and camel host populations was also designed, rigorously analysed, and fitted with data. The model was later extended to include the use of intervention measures, notably vaccination of humans and camels and the use of face mask by humans in public or when having frequent closed contacts with camels. The population-level impacts of these interventions, implemented in isolation or in combinations, were assessed. The study showed that focusing intervention resources on containing the MERS-CoV spread in the camel population would be more effective than on containing the spread in humans.

A pneumonia-like illness emerged late in 2019 (coined COVID-19), caused by SARSCoV-2, causing a devastating global pandemic on a scale never before seen sincethe 1918/1919 influenza pandemic. This dissertation contributes in providing deeper qualitative insights into the transmission dynamics and control of the disease in the United States. A basic mathematical model, which incorporates the key pertinent epidemiological features of SARS-CoV-2 and fitted using observed COVID-19 data, was designed and used to assess the population-level impacts of vaccination and face mask usage in mitigating the burden of the pandemic in the United States. Conditions for the existence and asymptotic stability of the various equilibria of the model were derived. The model was shown to undergo a vaccine-induced backward bifurcation when the associated reproduction number is less than one. Conditions for achieving vaccine-derived herd immunity were derived for three of the four FDA-approved vaccines (namely Pfizer, Moderna and Johnson & Johnson vaccine), and the vaccination coverage level needed to achieve it decreases with increasing coverage of moderately and highly-effective face masks. It was also shown that using face masks as a singular intervention strategy could lead to the elimination of the pandemic if moderate or highly-effective masks are prioritized and pandemic elimination prospects are greatly enhanced if the vaccination program is combined with a face mask use strategy that emphasizes the use of moderate to highly-effective masks with at least moderate coverage. The model was extended in Chapter 3 to allow for the assessment of the impacts of waning and boosting of vaccine-derived and natural immunity against the BA.1 Omicron variant of SARS-CoV-2. It was shown that vaccine-derived herd immunity can be achieved in the United States via a vaccination-boosting strategy which entails fully vaccinating at least 72% of the susceptible populace. Boosting of vaccine-derived immunity was shown to be more beneficial than boosting of natural immunity. Overall, this study showed that the prospects of the elimination of the pandemic in the United States were highly promising using the two intervention measures.

Malaria is a deadly, infectious, parasitic disease which is caused by Plasmodium parasites and transmitted between humans via the bite of adult female Anopheles mosquitoes. The primary insecticide-based interventions used to control malaria are indoor residual spraying (IRS) and long-lasting insecticide nets (LLINs). Larvicides are another insecticide-based intervention which is less commonly used. In this study, a mathematical model for malaria transmission dynamics in an endemic region which incorporates the use of IRS, LLINS, and larvicides is presented. The model is rigorously analyzed to gain insight into the asymptotic stability of the disease-free equilibrium. Simulations of the model show that individual insecticide-based interventions will not realistically control malaria in regions with high endemicity, but an integrated vector management strategy involving the use of multiple interventions could lead to the effective control of the disease. This study suggests that the use of larvicides alongside IRS and LLINs in endemic regions may be more effective than using only IRS and LLINs.

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.

Dengue is a mosquito-borne arboviral disease that causes significant public health burden in many trophical and sub-tropical parts of the world (where dengue is endemic). This dissertation is based on using mathematical modeling approaches, coupled with rigorous analysis and computation, to study the transmission dynamics and control of dengue disease. In Chapter 2, a new deterministic model was designed and used to assess the impact of local fluctuation of temperature and mosquito vertical (transvasorial) transmission on the population abundance of dengue mosquitoes and disease in a population. The model, which takes the form of a deterministic system of nonlinear differential equations, was parametrized using data from the Chiang Mai province of Thailand. The disease-free equilibrium of the model was shown to be globally-asymptotically stable when a certain epidemiological quantity is less than unity. Vertical transmission was shown to only have marginal impact on the disease dynamics, and its effect is temperature-dependent. Dengue burden in the province is maximized when the mean monthly temperature lie in the range [26-28] C. A new deterministic model was designed in Chapter 3 to assess the impact of the release of Wolbachia-infected mosquitoes on curtailing the mosquito population and dengue disease in a population. The model, which stratifies the mosquito population in terms of sex and Wolbachia-infection status, was rigorously analysed to characterize the bifurcation property of the model as well as the asymptotic stability of the various disease-free equilibria. Simulations, using Wolbachia-based mosquito control from Queensland, Australia, showed that the frequent release of mosquitoes infected with the bacterium can lead to the effective control of the local wild mosquito population, and that such effective control increases with increasing number of Wolbachia-infected mosquitoes released (up to 90% reduction in the wild mosquito population, from their baseline values, can be achieved). It was also shown that the well-known feature of cytoplasmic incompatibility has very little effect on the effectiveness of the Wolbachia-based mosquito control.

Cancer is a disease involving abnormal growth of cells. Its growth dynamics is perplexing. Mathematical modeling is a way to shed light on this progress and its medical treatments. This dissertation is to study cancer invasion in time and space using a mathematical approach. Chapter 1 presents a detailed review of literature on cancer modeling.

Chapter 2 focuses sorely on time where the escape of a generic cancer out of immune control is described by stochastic delayed differential equations (SDDEs). Without time delay and noise, this system demonstrates bistability. The effects of response time of the immune system and stochasticity in the tumor proliferation rate are studied by including delay and noise in the model. Stability, persistence and extinction of the tumor are analyzed. The result shows that both time delay and noise can induce the transition from low tumor burden equilibrium to high tumor equilibrium. The aforementioned work has been published (Han et al., 2019b).

In Chapter 3, Glioblastoma multiforme (GBM) is studied using a partial differential equation (PDE) model. GBM is an aggressive brain cancer with a grim prognosis. A mathematical model of GBM growth with explicit motility, birth, and death processes is proposed. A novel method is developed to approximate key characteristics of the wave profile, which can be compared with MRI data. Several test cases of MRI data of GBM patients are used to yield personalized parameterizations of the model. The aforementioned work has been published (Han et al., 2019a).

Chapter 4 presents an innovative way of forecasting spatial cancer invasion. Most mathematical models, including the ones described in previous chapters, are formulated based on strong assumptions, which are hard, if not impossible, to verify due to complexity of biological processes and lack of quality data. Instead, a nonparametric forecasting method using Gaussian processes is proposed. By exploiting the local nature of the spatio-temporal process, sparse (in terms of time) data is sufficient for forecasting. Desirable properties of Gaussian processes facilitate selection of the size of the local neighborhood and computationally efficient propagation of uncertainty. The method is tested on synthetic data and demonstrates promising results.

The analysis focuses on a two-population, three-dimensional model that attempts to accurately model the growth and diffusion of glioblastoma multiforme (GBM), a highly invasive brain cancer, throughout the brain. Analysis into the sensitivity of the model to

changes in the diffusion, growth, and death parameters was performed, in order to find a set of parameter values that accurately model observed tumor growth for a given patient. Additional changes were made to the diffusion parameters to account for the arrangement of nerve tracts in the brain, resulting in varying rates of diffusion. In general, small changes in the growth rates had a large impact on the outcome of the simulations, and for each patient there exists a set of parameters that allow the model to simulate a tumor that matches observed tumor growth in the patient over a period of two or three months. Furthermore, these results are more accurate with anisotropic diffusion, rather than isotropic diffusion. However, these parameters lead to inaccurate results for patients with tumors that undergo no observable growth over the given time interval. While it is possible to simulate long-term tumor growth, the simulation requires multiple comparisons to available MRI scans in order to find a set of parameters that provide an accurate prognosis.

Although extracellular throughout their lifecycle, trypanosomes are able to persist despite strong host immune responses through a process known as antigenic variation involving a large, highly diverse family of surface glycopro- tein (VSG) genes, only one of which is expressed at a time. Previous studies have used mathematical models to investigate the relationship between VSG switching and the dynamics of trypanosome infections, but none have explored the role of multiple VSG expression sites or the contribution of mosaic gene conversion events involving VSG pseudogenes.

This dissertation examines six different models in the field of econophysics using interacting particle systems as the basis of exploration. In each model examined, the underlying structure is a graph G = (V , E ), where each x ∈ V represents an individual who is characterized by the number of coins in her possession at time t. At each time step t, an edge (x, y) ∈ E is chosen at random, resulting in an exchange of coins between individuals x and y according to the rules of the model. Random variables ξt, and ξt(x) keep track of the current configuration and number of coins individual x has at time t respectively. Of particular interest is the distribution of coins in the long run. Considered first are the uniform reshuffling model, immediate exchange model and model with saving propensity. For each of these models, the number of coins an individual can have is nonnegative and the total number of coins in the system is conserved for all time. It is shown here that the distribution of coins converges to the exponential distribution, gamma distribution and a pseudo gamma distribution respectively. The next two models introduce debt, however, the total number of coins again remains fixed. It is shown here that when there is an individual debt limit, the number of coins per individual converges to a shifted exponential distribution. Alternatively, when a collective debt limit is imposed on the whole population, a heuristic argument is given supporting the conjecture that the distribution of coins converges to an asymmetric Laplace distribution. The final model considered focuses on the effect of cooperation on a population. Unlike the previous models discussed here, the total number of coins in the system at any given time is not bounded and the process evolves in continuous time rather than in discrete time. For this model, death of an individual will occur if they run out of coins. It is shown here that the survival probability for the population is impacted by the level of cooperation along with how productive the population is as whole.