Biological Engineering electronic theses and dissertations - Engineering (MU)
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The items in this collection are the theses and dissertations written by students of the Department of Biological Engineering. Some items may be viewed only by members of the University of Missouri System and/or University of Missouri-Columbia. Click on one of the browse buttons above for a complete listing of the works.
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Item Multiplex interrogration of protein-protein interactions in membrane-expressed multiprotein complexes(University of Missouri--Columbia, 2025) Zaidi, Melissa Taous; Schrum, Adam G.[EMBARGOED UNTIL 12/01/2026] Intricate protein-protein interaction (PPI) networks coordinate cellular functions and govern the specificity of signal transduction. Distinct PPI network signatures can discern pathological states from healthy conditions, yet extracting this information from small clinical samples or rare cell populations remains technically challenging. Conventional PPI methods are often limited in throughput, typically interrogating one interaction at a time, require large sample volumes, extensive purification, or the introduction of tags and labels that can perturb native interactions. They are also technically complex, demanding specialized equipment and expertise, which limits adoptability and broad application. These constraints highlight the need for sensitive, multiplexed, and accessible platforms capable of simultaneously measuring multiple PPIs in physiologically relevant contexts. Here, we report the development and application of multiplexed immunoprecipitation detected by electrochemiluminescence (MIP-ECL), a plate-based ELISA procedure designed for ultrasensitive detection of PPIs from minimal biosamples using a Mesoscale QuickPlex platform. We focused on the T cell antigen receptor (TCR)/CD3 due to its central role in immunological tolerance and immunity. Technical development included validation of capture antibodies, assessment of capture affinity, and optimization of multiplex assay parameters. MIP-ECL assay optimization enabled remarkable sensitivity, allowing the detection of zepto-moles of native multiprotein complexes from physiological sources, and demonstrated that capture reagents spanning a range of affinities could be employed, with greatest sensitivity correlating with highest affinity. Using MIP-ECL, TCR/CD3 complexes marking leukemia in a mouse transplant model were detected in blood from pre-symptomatic mice as early as three days post-tumor injection. In the CD3δ knock-out mouse model of immunodeficiency, MIP-ECL revealed how subunit loss was accommodated within rare and poorly functional peripheral T cells. Furthermore, MIP-ECL uncovered a previously unrecognized co receptor (CD4:CD8α) co-association. This observation provides preliminary evidence of novel immunological interactions and illustrates MIP-ECL's potential as a PPI discovery tool. Taken together, this work establishes MIP-ECL as a versatile, ultrasensitive, and adoptable platform for the validation, hypothesis-driven experimentation and discovery-driven mapping of PPIs within multiprotein complexes. By enabling analysis of rare cells and small physiological samples, MIP-ECL provides new opportunities to explore PPI networks, uncover previously unappreciated interactions, and advance our understanding of PPI in health and disease. We propose that our assay will permit detailed network analysis that has the potential to reveal context-dependent modulations in multiprotein signaling, providing insights that could significantly inform and refine pharmacological intervention strategiesItem Closed-loop optogenetic neuromodulation based brain-machine interfaces dissecting dopaminergic reinforcement learning circuits of the basal ganglia and developing translational therapies for ALS-related dysphagia(University of Missouri--Columbia, 2025) Basak, Apaala; Lever, Teresa E.; Sengupta, Shramik[EMBARGOED UNTIL 12/01/2026] This dissertation presents an integrated framework that bridges systems neuroscience and translational bioengineering to advance closed-loop optogenetic neuromodulation. The objective was to dissect cell-type-specific corticostriatal dopaminergic mechanisms of reinforcement learning and develop a translational approach to delay bulbar motor function degeneration in amyotrophic lateral sclerosis (ALS) related dysphagia. The work begins with the design and validation of two open-source engineering platforms that enable precise, accessible experimentation: (i) AROMATS (Arduino-based Rodent Olfactory Manipulation and Training System), a fully programmable behavioral interface that delivers millisecond-synchronized stimuli during Go/No-Go and reinforcement tasks, and (ii) a low-cost optoelectronic fiber-electrode assembly, optimized for simultaneous optical stimulation and neural recording in freely behaving mice. Together, these tools form the technical foundation for the experimental and translational studies that follow. Using these platforms, the first research component delineates how D1- and D2-expressing medium spiny neuron (MSN) pathways in the dorsomedial and dorsolateral striatum differentially shape reinforcement learning, motivation, and motor vigor. Optogenetic activation of D1-MSNs promoted persistent approach behavior, increased response rates, and enhanced reward engagement, whereas D2-MSN stimulation induced behavioral inhibition and slowed action initiation without disrupting task accuracy. Together, these findings reveal a functional gradient across striatal subregions that governs the balance between flexible and habitual control. The second research component translates this mechanistic insight to therapy, using targeted optogenetic excitation of hypoglossal motor units to counteract tongue weakness in ALS. Anesthetized strain gauge recordings confirmed robust, light-evoked mechanical contractions of the tongue in symptomatic and end-stage mice, establishing proof-ofconcept for preserving bulbar motor function through minimally invasive, light-based neuromodulation. Collectively, this work advances our mechanistic understanding of reinforcement learning circuits while pioneering adaptive, closed-loop neuromodulation strategies that connect computational theory with clinically relevant neural engineering.Item Engineering delivery systems for the treatment of Non-Hodgkin lymphoma(University of Missouri--Columbia, 2025) Shelton, Joshua; Ulery, Bret[EMBARGOED UNTIL 08/01/2026] Hematological cancers, including various leukemias and lymphomas, are among the top 10 cancers diagnosed in people. The leukemia and lymphoma society estimates that there are nearly 1.7 million people in the United States living with or in remission from hematological cancers. The frontline therapeutics for these diseases usually consist of conventional chemotherapeutics, such as RCHOP (i.e., Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone), a commonly used therapeutic regimen for many Non-Hodgkin lymphomas. While therapeutic remission can occur in 50% - 80% of these patients, nearly half are expected to develop relapsing or refractory disease. There exists a clear clinical need to generate targeted therapeutics that avoid undesirable side effects as well as can sufficiently address primary cancer to prevent follow-on disease. To address this issue, peptides have emerged in recent years as a novel improvement in cancer treatment, however, these drugs are limited by their poor cell penetration and serum instability. Lipidation of peptides, producing peptide amphiphiles, has been shown to allow for hydrophobically-driven self-assembly into peptide amphiphile micelles. There are many advantages to employing peptide amphiphile micelles as drug delivery devices, including improved serum stability, higher local therapeutic concentration, and co-loading of other materials, such as chemotherapeutic drugs or multiple PAs. In this dissertation, materials will be presented that utilize the peptide amphiphile micelle platform for the treatment of cancer along with the optimization of targeting elements that may be used to improve their drug delivery capacity. First to be discussed is the delivery of a novel, cytotoxic peptide (i.e., POSH(3.3A)-Tat) by micelle for the treatment of Non- Hodgkin lymphoma and multiple myeloma. This will be followed by foundational work focused on the targeting of Non-Hodgkin lymphoma using aptamers. Finally, a complement to aptamers in the antibody-mediated targeting of peptide amphiphile micelles will be covered.Item Development of novel biomarkers for assessing pulmonary and cardiopulmonary function utilizing hyperpolarized gas MRI(University of Missouri--Columbia, 2025) García Delgado, Gabriela María; Thomen, Robert P.[EMBARGOED UNTIL 08/01/2026] Magnetic Resonance Imaging (MRI) is an advanced imaging technique that transformed the field of Radiology. Its' capability of providing such high-resolution imaging without exposing patients to ionizing radiation changed the field of medical diagnosis and treatment. The presence of this imaging modality has allowed scientists to expand on quantitative methods to further improve the precision and application of MRI in disease management. Although an excellent imaging modality, it is unable to provide informative pulmonary images regarding lung structure and lung function due to low proton density in the lungs. HPG MRI is an innovative imaging modality that is now clinically used and allows for the visualization of ventilation capabilities and gas exchange efficiency in patients. Compared to the common clinical standard for assessing lung structure and lung function, pulmonary function tests (PFTs), HPG MRI provides regional specificity that PFTs lack. This dissertation presents various novel quantification methods utilizing HPG MRI so that personalized medicine and cost reduction can be achieved when used in clinical and research settings. The first novel technique developed and presented in this dissertation involves the development of a three-dimensional spatial ventilation defect focality/sparseness quantifier utilizing HPG MRI, a Cluster Index (CI). This technique was validated utilizing synthesized spherical data and synthesized lung defects to assimilate real pulmonary ventilation defects. This new method was also utilized to compare CIs among different pulmonary diseases such as ventilation images from asthmatic, CF, and COPD subjects. This method may allow for the investigation of potential information regarding underlying pathophysiology that has yet to be found and potential differences in defect focality across different diseases and disease severities. The second study presented in this dissertation involved the development of a graphical user interface that would allow for the assessment of reader manually selected thresholds and compare these to existing VDP quantifying methods. Image features and potential influence of these in threshold selections were also assessed and compared among readers. The results provide insight into what would be the best VDP quantifying method, if the existing thresholds match visual assessments, and the agreement between reader selected thresholds and visually estimated VDPs. The third technique developed and presented entails the performance of singular value decomposition to construct low-noise approximation of FID data, and time domain curve fitting on all free induction decays to obtain a dynamic RBC/membrane ratio and oscillation amplitude quantification. This new marker has the potential to be used as an imaging biomarker to assess disease severity, treatment response, and allow for reduced costs in HPG MRI due to the denoising properties in SVD. The findings from this dissertation will contribute to the development of new imaging biomarker methods to quantify defect focality, disease state/progression, and a standardized DP quantifying protocol.Item The exploration of pulmonary dynamics in e-cigarette users utilizing hyperpolarized gas MRI(University of Missouri--Columbia, 2025) Parks, Isabella; Thomen, Robert[EMBARGOED UNTIL 05/01/2026] The lungs are remarkably efficient organs, designed to sustain life through continuous exchange of gases essential to metabolism and cellular function. From birth onward, they operate with little conscious effort, yet they remain susceptible to a wide range of environmental and behavioral influences. As respiratory illnesses affect a growing portion of the global population, (Collaborators., 2023) the ability to monitor, evaluate, and preserve pulmonary function is becoming increasingly critical. Advances in diagnostic imaging, particularly those that assess not just anatomical but also functional aspects of the lungs, are central to improving early detection and intervention in chronic and emerging respiratory conditions. The increasing prevalence of vaping among young adults (Becker TD, 2022) has catalyzed a new wave of concern regarding respiratory health, prompting researchers and clinicians to interrogate the long-term consequences of this relatively modern practice. (Muthumalage, 2019) Though e-cigarettes are often marketed as harm-reduction devices, a safer alternative to combustible tobacco, accumulating evidence suggests that their inhaled constituents may not be benign. Early studies have begun to uncover subtle disruptions in lung physiology linked to vaping (Casey AM, 2020) yet the field remains nascent, particularly when it comes to individuals who have never or rarely engaged in traditional smoking. This research seeks to bridge that gap by investigating whether measurable changes in lung function occur among young adults who regularly vape but have little or no prior exposure to traditional cigarettes. Specifically, this study examines whether hyperpolarized xenon magnetic resonance imaging, a modality capable of visualizing both ventilation and gas exchange, can detect early biomarkers of pulmonary impairment in this cohort. It also investigates whether these biomarkers correlate with reported respiratory symptoms, or if the symptomatology reflects a mismatch between physiological data and perceived impairment, potentially implicating non-pulmonary origins. A cross-sectional study design was employed to enroll individuals aged 18--30 who reported at least one year of regular e-cigarette use and negligible, if any, history of combustible tobacco exposure. Each participant underwent hyperpolarized xenon magnetic resonance imaging to quantify ventilation heterogeneity, gas exchange efficiency, and potential airway abnormalities. Complementary surveys and exposure assessments were administered to gather detailed information on vaping behaviors, including device type, usage frequency, duration, and nicotine concentration, as well as relevant environmental exposures. These datasets supported a multifactorial analysis of potential contributors to pulmonary dysfunction. Data from the vaping cohort were subsequently compared to previously acquired datasets from healthy, age-matched controls to evaluate deviations in lung function metrics. This project was structured around two primary aims. The first was to identify imaging biomarkers of lung function associated with clinical symptomatology in e-cigarette users, providing insight into subclinical physiological changes that may precede overt disease. The second was to examine how environmental and behavioral factors contributed to these findings by integrating imaging data with participant-specific behavioral and exposure profiles.