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The Role of Septin Filaments in Neural Crest Cell Migration
No full textSeptin filaments are the fourth member of the cytoskeleton, along with actin microfilaments, microtubules, and intermediate filaments. Since their discovery over 50 years ago, septin filaments have been found to play integral roles in different cellular processes. Recent studies in metastatic cancer cell lines have reported that septin filaments promote cell migration, but a mechanism for their regulation of directed cell migration is still unclear. In this thesis, we utilize the highly similar and established cell migration model of neural crest cells to answer this question.
This thesis is structured into three related projects that examine the relationship between septin filaments and their interaction partners in coordinating directed cell migration. The first project focuses on the requirement of septin filament assembly in neural crest cells and the interaction of septin filaments with actin and Cdc42ep1 in neural crest cell migration. Specifically, we found that Cdc42ep1 and septin filaments reciprocally regulate each other and that septin filaments regulate the persistent orientation of actin stress fiber formation and contraction necessary for neural crest cell migration. The second project investigates the role of the actin-binding protein myosin II as a mediator for the septin regulation of actin stress fibers. We found that the direct interaction between septins and myosin II is required to support the persistent migration of neural crest cells. The third project focuses on PAR-1 kinase and its regulation of Cdc42ep1 activity in neural crest cells. We found that PAR-1 kinase is required for neural crest cell migration and that PAR-1 phosphorylation regulates the subcellular organization of Cdc42ep1 in a manner reminiscent of the septin regulation of Cdc42ep1. Together, we propose a model in which septin filaments, Cdc42ep1, and actomyosin coordinate in directed and effective migration of neural crest cells. Importantly, this work reveals the fundamental role of septin filaments in coordinating cytoskeletal dynamics for directed cell migration. This activity is likely conserved during metastatic cancer cell migration
A hierarchical approach to multi-messenger gravitational wave searches
No full textMulti-messenger gravitational wave astronomy became a booming field after the joint detection of GW/GRB 170817. Gamma-ray, x-ray, and neutrinos are good multi-messenger complements to gravitational wave searches. Where gravitational-wave localization can span tens to hundreds of square degrees in the sky, these other messengers tend to have far smaller error regions and their pinpointed time and location of arrival allow for targeted follow-up searches with gravitational wave detectors.
In this thesis, I investigate these cosmic messengers with LIGO-Virgo-KAGRA gravitational wave data to search for the messengers’ potential progenitor: neutron star or black hole collisions. Matched filtering searches are a key technique in the effort to detect gravitational waves coinci-
dent with gamma-ray bursts and fast radio bursts. I begin by reviewing the field of gravitational wave astronomy. I then explore the potential multi-messenger counterparts to gravitational waves: gamma-ray bursts, neutrinos, fast radio bursts, as well as multi-band observations of compact binary merger. I then present my work in multi-messenger searches for gravitational waves with gamma-ray bursts and fast radio bursts in LIGO-Virgo-KAGRA data using the targeted gravitational wave analysis, PyGRB. The principal limiting factor for PyGRB is its computational cost. The cost makes it infeasible to process hundreds of multi-messenger events. So in the final chapter, I will introduce efforts to build a hierarchical search, PyNu, to process these events for follow-up with the established multi-messenger pipeline, PyGRB. The goal is to process larger multi-messenger catalogs than PyGRB while retaining the unique sensitivity offered by targeted matched filtering. I present the methods for PyNu as well as the results of my analysis of its sensitivity to gravitational wave signals. Finally, I discuss future prospects for multi messenger astronomy with gravitational waves through PyNu. PyNu will improve the reach of PyGRB and expand our view of the multi-messenger sky at an affordable computational cost.Ph.D.Physic
Technologies For Next-Generation Optical Communication Systems
No full textThe objective of the proposed research is to improve two disparate aspects of optical communication: multiplexing flexibility and bandwidth density of optical communication systems by developing and experimentally demonstrating power division multiplexing and high-speed integrated microring modulators. Power division multiplexing improves the multiplexing flexibility of the optical network by permitting optical communication signals that share the same carrier frequency to be added together at disparate transmitters that do not cooperate with each other. This work demonstrates such a signal can be demodulated at a single standard coherent transmitter, and analyzes the effect of differing polarization states, baud rates, and chromatic dispersion between the two signals. The bandwidth density of optical communication links is improved by characterizing space- and energy- efficient high-speed microring modulators fabricated on a foundry platform. An experimental tool known as a Lightwave Component Analyzer is developed to assess their frequency responses up to 110 GHz. Several additional technologies including blind subcarrier demodulation, an integrated optoelectronic oscillator, and an integrated linearized modulator are also considered
Investigating Reaction Mechanisms of Next-Generation Active Materials for Low-Temperature Lithium-Ion Batteries
No full textLithium-ion batteries have become ubiquitous in most energy storage applications because of their high energy density and long cycle life, enabled by the intercalation chemistry of the electrodes that are used. However, interest in novel lithium-based chemistries has increased in recent years, as engineering improvements have reached the theoretical limits the intercalation materials. In particular, current lithium-ion battery chemistries only operate with ideal performance in a narrow temperature range around room temperature, preventing effective energy storage in many environments. At low temperature, transport and kinetic limitations prevent intercalation of lithium ions in electrode materials, and many commercial electrolytes freeze below 0 oC. This necessitates the use of extensive heating systems in low temperature applications, such as space exploration and electric aviation.
Materials that electrochemically alloy with lithium, known as alloy electrodes, have been studied since the inception of lithium-ion batteries because of their high specific capacity. However, they were abandoned early in the development of commercial batteries in favor of intercalation materials due to their rapid mechanical degradation. Despite this, research on these materials continues and they show significant potential to expand the low temperature range of batteries. The vast majority of research on these materials focuses on their room temperature electrochemical behavior. This dissertation aims to fill that gap by investigating the
electrochemical, morphological, and mechanistic evolution of alloy anodes at low temperatures to guide future engineering of low temperature batteries.
First, the electrochemical behavior of three common alloy anodes was investigated to determine if lithium alloys are successful replacements for graphite in lithium-ion batteries, as well as to better understand the low temperature processes that influence performance. I showed that these lithium alloys could be charged and discharged down at temperatures down to -40 oC with ten times higher specific capacity than graphite on the first cycle. Antimony, in particular, demonstrates improved low temperature performance and cycling stability compared to other alloy materials, in part due to its high electrode potential. Three-electrode cells with a lithium metal reference electrode were used to determine the influence of the counter electrode on low temperature measurements, showing that lithium plating and stripping at the counter electrode can obscure the effects of the working electrode of interest on the voltage profile. Finally, I used the galvanostatic intermittent titration technique to elucidate the processes which dominate overpotential at low temperatures and found that kinetic and thermodynamic limitations are alloy- dependent and can change significantly from one cycle to the next and between charge and discharge, indicating mechanistic changes during early stages of cycling.
Next, I investigated morphological and mechanistic changes of alloy foil anodes when lithiated and delithiated at various temperatures. Ex-situ characterization revealed temperature dependent fracture behavior for both indium and tin alloy anodes, with increased degree of surface fracture occurring at low temperatures. Unexpectedly, larger Coulombic efficiencies were achieved in cells with tin electrodes cycled at -20 oC compared to 60 or 20 oC, despite the extreme morphological evolution of the tin anode at low temperatures and the high thermal energy available at higher temperatures to drive lithium diffusion and phase propagation. Cryogenic focused ion beam milling revealed that both tin and indium demonstrate similar trends in lithiation and delithiation behavior as a function of temperature. Both tin and indium exhibit homogeneous lithiation and delithiation with planar reaction fronts between unreacted, lithiated, and delithiated phases, which likely contributes to both the high Coulombic efficiency and increase in extent of fracture seen at low temperature. At high temperatures, inhomogeneous lithiation and delithiation behavior occurs with indium forming distinct lithiated nuclei separated by unreacted regions, while tin shows clear evidence of lithium trapping, which results in low Coulombic efficiency. Chronoamperometry and optical microscopy were used to reveal temperature- and composition- dependent phase nucleation phenomena, which explain the changes in homogeneity of lithiation and delithiation as a function of temperature.
Overall, the work completed in this dissertation indicates that lithium alloy anodes cam be an effective replacement for graphite to enable low temperature batteries. Furthermore, these findings provide fundamental understanding of the temperature-dependency of the reaction mechanisms and morphological evolution of alloy materials.Ph.D.Materials Science and Engineerin
Locoregional and systemic immunomodulation with intratumoral TCR agonism
No full textCancer immunotherapies have revolutionized cancer treatment however, success in solid
tumors remains limited. With many solid tumors exhibiting heterogeneity and rapid
growth, developing an easily accessible, off the shelf, potent T cell modulator that
leverages the immune system’s intrinsic anti-tumor mechanisms to quickly to combat
tumor progression is advantageous. Here we demonstrate a single dose of aCD3 induces
potent tumor control in a B16F10 orthotopic tumor model and is well tolerated. Not only
does this antigen agnostic TCR agonism strategy result in mobilization of therapeutic T
cell populations into the circulation and increase tumor infiltration of effector CD8 T cell
subsets, but it also synergizes with current cancer immunotherapies, namely immune
checkpoint blockade (ICB) aPD-1 improving overall survival. Further, therapy was not
restricted to an intratumoral route of administration, where tumor draining lymph node
(TDLN) directed administration resulted in the expansion of effector CD8 T cells in the
circulation and subsequent tumor infiltration. This minimally invasive therapeutic strategy
induces remodeling of CD8 T cell subsets in both the TDLN and NDLN indicating both
local and systemic immune modulation. The quality of CD8 T cell subset mobilized into
the circulation has strong implications on the efficacy of current cancer immunotherapies,
therefore understanding the flux of key immune population from lymphoid tissues through
the circulation into the tumor is essential in improving cancer immunotherapies.Ph.D.Biomedical Engineerin
Using synthetic biology and experimental evolution to reconstruct major evolutionary innovations
No full textEvolutionary innovations have shaped the history of life on Earth. This thesis uses synthetic biology and experimental evolution to explore the origin of phototrophic metabolism and the evolution of multicellularity in yeast.
The first part of this work examines whether a retinalophototrophic system can be readily acquired by an organism with no prior history of phototrophy. Unicellular Saccharomyces cerevisiae was transformed into a facultative photoheterotroph by inserting a rhodopsin into the yeast vacuole, allowing light to translocate protons into the vacuolar compartment, a function typically driven by consuming ATP. I show that yeast-bearing rhodopsins gain a selective advantage when grown under green light, growing more rapidly than their non-phototrophic ancestor. This work demonstrates the remarkable ease with which rhodopsins may be horizontally transferred, providing novel biological function without the need for prior evolutionary optimization.
Next, I explored the role of nascent life cycle structures on the evolution of collective-level adaptations. All complex multicellular lineages (animals, plants, brown algae, red algae and fungi) develop clonally and are obligately multicellular. I used S. cerevisiae to engineer a facultative life cycle (alternating between single cell and multicellular clusters) and compared it to obligate multicellularity. Using experimental evolution, I found that all obligately multicellular populations evolved larger multicellular size and tetraploidy, a known multicellular trait. These traits were severely constrained in facultative populations, despite tetraploidy being strongly beneficial across the full life cycle. I show that facultative life cycles create an establishment barrier through population asymmetries due to group formation reducing the number of units of selection, coupled with cell-level selection dominating group-level selection. These findings demonstrate that the presence of a unicellular stage creates genetic barriers to multicellular adaptations, which may explain why facultatively multicellular organisms have remained simple compared to complex multicellularity seen only in obligately multicellular organisms.
Together, this thesis advances our understanding of early steps in evolutionary innovations, with a focus on the origin of phototrophy and the role of obligate life cycles during the transition to multicellularity
Modeling and Analytics for Resource Allocation, Interventions, and Equity in Public Health
No full textEffective, efficient, and equitable planning is crucial during public health challenges to minimize the loss of life, health, and well-being in our communities. This thesis explores the application of modeling and analytics to enhance public health decision-making in the infectious disease space. Specifically, we evaluate the allocation of limited resources, the effectiveness of public health interventions, and racial and ethnic disparities in health outcomes during the COVID-19 pandemic and infectious disease outbreaks.
In Chapter 2, we assess a resource allocation framework when resources are limited, using the allocation of COVID-19 vaccines as a case study. We develop an extended SIR compartmental model to evaluate the benefits of using serology testing to prioritize the vaccination of those who are susceptible to infection across different pandemic scenarios. These scenarios vary by disease transmissibility, vaccine quantity and timing of availability, and serology testing capacity.
In Chapter 3, we develop an agent-based model to simulate the spread of infectious diseases on cruise ships, incorporating the demographics of both the passengers and crew members. We construct contact networks that capture and replicate interactions on ships, and ultimately, how diseases spread within this environment. We present two case studies evaluating COVID-19 and norovirus outbreaks on cruise ships. The model evaluates the effectiveness of pharmaceutical and non-pharmaceutical interventions in reducing cases on board.
In Chapter 4, we examine racial and ethnic disparities in COVID-19 vaccination, deaths, and hospitalizations in the state of Georgia. We evaluate whether certain racial and ethnic groups experienced disproportionately adverse outcomes during the pandemic when stratifying by county rural/urban classification and vaccination status. This approach, which evaluates disparities at a finer geographic scale while accounting for differences in vaccination uptake across racial/ethnic groups, provides additional insights into trends observed at the national and state levels.
In Chapter 5, we analyze patterns of data missingness in COVID-19 vaccination records in Georgia. We focus on the absence of residence information for vaccine recipients and its impact on estimating vaccination rates for different population subgroups. We propose and compare data imputation methods to address the data missingness and, more accurately, estimate vaccination rates.Ph.D.Industrial Engineerin
Scholarship in Place
No full textInterview portion of Lost in the Stacks, episode 669. Features interviews with Dr. Yanni Loukissas, associate professor of digital media in the School of Literature, Media, and Communication at Georgia Tech, and Dr. Sylvia Janicki, who recently earned her PhD in Digital Media from Georgia Tech. They discuss spatial scholarship as described in their recent article, "Making Local Data Memoirs: Changing Orientations in Relation to Environmental Concerns." This episode is part of the Georgia Tech Media Arts Day 2026 programming.Interview portion of Lost in the Stacks, episode 669. Features interviews with Dr. Yanni Loukissas, associate professor of digital media in the School of Literature, Media, and Communication at Georgia Tech, and Dr. Sylvia Janicki, who recently earned her PhD in Digital Media from Georgia Tech. They discuss spatial scholarship as described in their recent article, "Making Local Data Memoirs: Changing Orientations in Relation to Environmental Concerns." This episode is part of the Georgia Tech Media Arts Day 2026 programming
A Probabilistic, Life Cycle-Based Approach for Technology Assessment of Hybrid-Electric Propulsion in Single-Aisle Aircraft
No full textThe aviation industry is at a pivotal juncture, facing the dual challenges of meeting rising global travel demand while significantly reducing its environmental footprint. Single-aisle aircraft currently account for more than half of annual climate-impacting aviation emissions and are projected to comprise over 75\% of all aircraft deliveries between 2024 and 2042. In response, the industry is exploring advanced technology development for the next generation of single-aisle aircraft. One technology of interest is hybrid-electric propulsion, and there are two key challenges to the successful development and deployment of a next-generation single-aisle aircraft powered by hybrid-electric propulsion.
The first challenge is that hybrid-electric propulsion systems are emergent and rely on rapidly-developing technologies for feasibility and viability. Thus, technological uncertainty associated with components of the hybrid-electric powertrain affects the design and performance of the overall aircraft. Current technology assessment approaches often disregard technological uncertainty, affecting vehicle design and quantified environmental performance. This dissertation addresses this research gap by directly quantifying how technological uncertainty impacts optimal design parameters and by comparing uncertainty management methods.
The second challenge is that aircraft powered by hybrid-electric propulsion may have unintended environmental impacts through life cycle effects. Current technology assessment approaches prioritize the reduction of fuel consumption, which is a potential benefit of hybrid-electric propulsion systems. However, electricity generation to supply the electrical energy storage systems of the hybrid-electric powertrain has its own environmental impacts, which should also be accounted for during analysis. Additionally, battery charging is not a perfectly efficient process, and batteries have operational life limits shorter than those of aircraft. Thus, the operational performance of batteries has environmental impacts that are also ignored by traditional technology assessment approaches.
This dissertation explores the benefits of the combined use of design under uncertainty approaches and life cycle assessment for technology assessment of single-aisle aircraft powered by hybrid-electric propulsion. A life cycle assessment module was developed and integrated with a hybrid-electric vehicle performance model to assess the value of the combined approach. Studies were executed in three research areas: vehicle design under uncertainty, life cycle-based evaluation, and life cycle-based design under uncertainty. Results from the three research areas were shown to support the overarching research hypothesis, which stated that the combined use of uncertainty-informed design and life cycle assessment during technology assessment yields hybrid-electric aircraft design solutions that are significantly different—in both design parameters and environmental impact estimates—from those derived using a vehicle-level, deterministic approach. Furthermore, the integrated method provides more holistic insights for technology assessment and decision-making. Based on these findings, this dissertation concludes with an updated technology assessment approach, which can be leveraged in future studies of emerging aviation technologies.Ph.D.Aerospace Engineerin
One-Step Flow Maps for Real-Time Fluid Simulation with Dynamic Boundaries
No full textAs modern Graphics Processing Unit (GPU) evolve, video games are adopting more advanced rendering technologies to produce high-fidelity image synthesis. To match this visual aesthetic, the physical simulation of dynamic effects is also required to achieve a higher degree of realism. This thesis introduces a high-precision fluid simulation method, flow map-based fluids, into the real-time graphics pipeline. The goal is to produce high quality, high vorticity smoke simulations suitable for video games, all while maintaining interactive frame rates. To achieve this, we first simplify the original, computationally expensive method by proposing a One-Step Flow Map (OFM). This modification reduces the cost of the high-precision simulation by using only a single integration sub-step per timestep. Furthermore, we combine our OFM solver with a real-time mesh voxelization pipeline. This allows solid objects, represented by standard triangle meshes, to apply dynamic boundary conditions to the fluid. By enabling the fluid to realistically interact with moving objects in the scene, this method significantly enhances the physical immersion of the simulation