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Undergraduate Research Opportunities Program

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Office of Undergraduate Education

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Publication Search Results

Now showing 1 - 10 of 165

The Phenotypic Response of Dendritic Cells to Gold Nanoparticles Treatments

(Georgia Institute of Technology, 2019-12) Dasgupta, Ayan

Immunotherapy research has been increasingly investigating the potential of gold nanoparticles (AuNPs). AuNPs pose new benefits in the medical field ranging from diagnostics to diseases treatment. AuNPs’ ability to infiltrate tissue and target immune cells makes their potential highly useful for new proposed personalized immunotherapies[1] regarding antigen specific targeting delivery, tracking capabilities in vivo [2][3], and more effective and direct vaccines [8]. AuNPs act as an adjuvant with the ability to elicit immuno-suppressive or immuno-activated responses depending on the treatment and characterization of the AuNPs. A promising application of AuNPs is their ability to interact with dendritic cells (DCs). DCs are antigen presenting cells (APCs) and play an integral part in both innate and adaptive immune responses. They work by internalizing and presenting antigens on their surface to other immune cells initiating an immunomodulatory response. In previous research, it has been shown that AuNPs engineered with surface molecules can the initiate maturation of immature DCs (iDCs). Depending on the surface molecules, AuNPs can mature iDCs to become either activated or tolerogenic DC phenotypes[1]. These matured DC phenotypes use the AuNP’s surface molecules to then elicit an immune response by presenting the surface molecules to other immune cells in addition to secreting chemokines and cytokines to enhance the immune response. Though AuNPs’ influence on the maturation of iDCs has been increasingly studied, it is still not well understood which is critical in order to develop effective personalized immunotherapies. In this study, the relationship between DC phenotypes and AuNP properties is analyzed in order to optimize the methods used to elicit specific immune responses. iDCs will be cultured and treated with AuNPs with various surface modifications which will then be analyzed to determine the phenotypic character of the cultured DCs. The cultured DCs are analyzed using high-throughput screening and flow cytometry to determine the surface molecules that have developed from the AuNP treatment which will determine which phenotype of the matured iDCs. This analysis will establish a relationship between various AuNP treatments and the resulting phenotypic development of DCs. This research will work towards standardizing maturation methods of DCs in vivo in order to control a patient’s immune system and its responses to fight off diseases and arm immune cells.
Pulsatile Flow System for Surgical Robotics

(Georgia Institute of Technology, 2019-12) Verma, Ankita

Surgical robotics is an evolving field where robotic medical devices are utilized to perform surgery either on or within the body. In order to mitigate errors that may occur during surgery due to the medical devices being used, testing environments are created for better development of the device and for clinical training. A Pulsatile Flow System (PFS) is a machine that recreates the physiological conditions of flow rate and pressure as the heart pumps blood, and can be created using materials such as pipes and motors. The research at hand developed a PFS and specifically focused on the electrical components of the system, using a motor, a motor controller, a flow sensor, and a circuit board. By creating code that is able to control the system and the speed at which the PFS functions, the system was able to pump water at 40 beats per minute through the circuit. Moving forward, the PFS can be improved to become an even more accurate model by including changes such as substituting the water in the system with a liquid of a similar viscosity to blood. The development of a machine like this is crucial in order to provide a cost effective system capable of imitating the human body in order to properly test surgical robots that travel through arteries in the body. Using an external testing environment will ensure that the devices created in the laboratory are properly developed before they are used in surgery, ensuring that the patient’s life is kept out of harm’s way.
Efficacy of an International Student Orientation Course

(Georgia Institute of Technology, 2019-12) Bell, Mark Reeves

Culture shock is a prominent phenomenon for international students when beginning college. The term ‘culture shock’ is defined as a negative emotional reaction caused by the overwhelming and confusing flood of unfamiliar behavior in a new culture. Culture shock induces stress through frustration with culture norms, and experiencing culture shock causes many struggles including language difficulties, homesickness, and social isolation. Culture shock is salient to undergrads because they are young and seemingly on their own immediately after they move. Moreover, American colleges and universities have dramatically increased their numbers of international students, especially students from culturally different eastern countries. These particular students have shown noticeable levels of culture shock during their first semester of college. This study was designed to determine the efficacy of a three-week international student orientation course for first-year international students. The first session introduced students to possible differences they might experience in the American culture and the social norms put in place. The second session introduced students to the wide variety of resources on and off campus. This was an informational session to help compensate for the shortened FASET orientation that international students receive. The third session introduced students to different role-playing scenarios, including negotiating a friendship, working in groups, and meeting a professor for office hours. Measurements for the efficacy included mental health surveys over seven weeks, pre- and post-course questions on culture shock, and course evaluations. Due to low participation, the quantitative analysis returned statistically non-significant results. Regardless, the study showed promise in future research.
Discovering potential combinational treatments of Amyotrophic Lateral Sclerosis (ALS) using a computational model of G93A mouse.

(Georgia Institute of Technology, 2019-12) Lee, Albert Jong

Instabilities in the regulatory mechanisms utilized by the superoxide dismutase 1 glycine 93 to alanine (SOD1 G93A) transgenic mouse to compensate for changes to the system have been postulated to play a considerable role in Amyotrophic Lateral Sclerosis (ALS) disease progression. However, there is currently no concrete evidence of such regulatory dysfunctions in the SOD1 G93A mouse. In order to study the complexity of ALS, a computational model of wild type (WT) mouse physiological regulation was developed using a combination of dynamic meta-analysis (DMA) and global optimization. Such model was shown to be able to predict the time dynamics of WT physiological functions. The method presented in this study will be used to construct a G93A model and can be further applied to other multifunctional diseases.
Investigation of the Cytokine and Chemokine Response of Dendritic Cells Following Gold Nanoparticle Treatments and Variations in Hydrogels

(Georgia Institute of Technology, 2019-12) Arya, Priya

Immunotherapies have significant potential for implementation towards personalized medicine through avenues such as vaccine, gene, and cancer applications. Dendritic cells are a major contributor in the immune system, functioning as antigen-presenting cells that aid in orchestrating the immune response towards pathogenic activators. Manipulation of these cells can allow for the optimization of immune responses, which can be achieved through tissue engineering and modulation via gold nanoparticles. This study seeks to provide a basis for elucidating the secretory responses of immature dendritic cells as they progress through maturation following treatment with modified gold nanoparticles. Additionally, findings are presented on the manipulation of dendritic cells with a variety of treatments such as PEGylation and thiolation to understand resulting effects on IL-10 expression. Biomaterial-based matrices are additionally investigated for their roles in dendritic cell viability and functionality – results of variation in weight percentage of hydrogels, used for dendritic cell encapsulation, will be shown. With some notable exceptions, such as IL-4, the majority of cytokine and chemokine expressions in experimental cell groups compared to baseline immature dendritic cell expression levels decreased. Future studies should continue to characterize and solidify this response, both with regard to modulation in hydrogels and gold nanoparticles. These studies can aid in paving the way for individualized treatment for autoimmune disorders.
Modeling the Left Heart: Finite Element Analysis and Fluid Structure Interaction Simulation on Mitral Regurgitation Patient Images

(Georgia Institute of Technology, 2019-08) Geil, Hannah Danielle

Mitral regurgitation affects over two million people in the US and can lead to heart failure, so research is needed to predict, diagnose, and treat this valvular disease. Thus, cardiac modeling in vitro includes mathematical, automated, and image-based models. Mathematical modeling requires assumptions that make it less accurate, and it takes too long to conduct to be clinically relevant. Automated modeling is faster but generally untrusted in the field. Image-based models are often patient specific and accurate but are rarely combined with computational models. Due to a need for an accurate and comprehensive model, this study used image-based modeling techniques and computational simulations of blood flow. Patient-specific images were used to create a three-dimensional model of the left heart. After segmentation, meshing, and defining boundary conditions, the model was run though a finite element analysis and a fluid structure interaction simulation. Nodes were then quantified to understand how the heart responded to simulation. Results showed that as pressure increased, stress and strain increased, and regurgitation area decreased. The results of this study have direct clinical applications; physicians can use the models as a guide when making decisions regarding diagnoses or surgical treatment.
Neuron-SpecificC Enolase as a Diagnostic Biomarker for TBI in Preclinical Trials: A systematic review

(Georgia Institute of Technology, 2019-05-16) Sofia, Connor J.

Traumatic brain injury (TBI) is the leading cause of death and disability among young adults. Thus, discovering a biomarker to assess the severity of TBI is an issue of immense clinical importance. This systematic review aims to evaluate the potential for neuron specific enolase (NSE) to identify TBI in animal studies. MEDLINE and Pubmed were searched for relevant literature up to January of 2017. Studies were included as part of the review if they included animal species, age, sex, injury severity, injury model, sampling site, number of animals per injury group, at least one outcome measure, and number of time points for recording the biomarker in question. Risk of bias was assessed by the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2). 3411 citations were screened, of which 20 were considered for final review. NSE was generally found to be a positive predictor for TBI. In preclinical trial data involving TBI, increased levels of NSE correlate with injury severity. Inconsistent data reporting standards and lack of consistency involving injury model hampered the success of this review; more trials with homogeneous data is required to attain statistical significance.
An Ex Vivo Model of Oxidative Stress Induced Trabecular Meshwork Dysfunction for Glaucomca Research

(Georgia Institute of Technology, 2019-05) Hardie, Rebecca

Affecting more than 70 million people worldwide, glaucoma is one of the leading causes of vision loss and blindness. Although the exact origins of glaucoma are still unknown, elevated intraocular pressure is a well-established risk factor. Intraocular pressure is primarily regulated by the trabecular meshwork, a tissue located in the anterior segment of the eye which drains aqueous humor. The cellularity of the trabecular meshwork is shown to be significantly reduced in glaucoma. This loss of cellularity presumably leads to reduced trabecular meshwork function and increased outflow resistance, which in turn leads to elevated intraocular pressure. In order to assess regenerative medicine therapies for glaucoma, the damage to the trabecular meshwork observed in glaucoma must be properly modeled. This study demonstrates that oxidative stress caused by hydrogen peroxide can reduce trabecular meshwork cellularity to glaucomatous levels in a porcine anterior chamber organ culture model. The diminished trabecular meshwork cellularity resulted in a loss of intraocular pressure homeostasis and the hydrogen peroxide treatment did not permanently damage the trabecular meshwork. This porcine organ culture model provides a platform for evaluating trabecular meshwork regenerative medicine therapies that could be possibly used to treat glaucoma.
Induced Pluripotent Stem Cell-based in vitro Modeling of the Osteogenesis and Chondrogenesis of Juvenile Osteochondritis Dissecans

(Georgia Institute of Technology, 2019-05) Nations, Catriana C.

The application of pluripotent stem-cell based in vitro models has become increasingly popular in medical research, especially for situations in which animal modeling is not sufficient to accurately describe the condition or for diseases where there is little research demonstrating the relationships between disease phenotype, pathological cellular mechanisms, and gene expression. Such is the case with Juvenile Osteochondritis Dissecans (JOCD), a degenerative bone disease that predominately affects the knee joints of children and progresses to early onset osteoarthritis. Previous research has involved the use of animal models or diseases similar to JOCD, but there has been little to no focus on the cellular mechanisms of this condition. Therefore, this study aimed to elucidate the cellular pathophysiology of JOCD as well as provide a test bed for future therapeutic interventions. We hypothesized that our iPSC in vitro models of JOCD would show protein dysfunction and accumulation in the rough endoplasmic reticulum as a hallmark of the disease, as previously shown in familial and equine OCD.
Hyaluronan Physically Mediates Cell Adhesion

(Georgia Institute of Technology, 2019-05) Keate, Rebecca

Cell adhesion is the fundamental process underlying all basic life processes. While structures that enhance cell adhesion strength, such as focal adhesions, have been widely characterized, influences decreasing cell adhesion strength have yet to be explored. Hyaluronan (HA), a ubiquitous polymer in extracellular matrices, is hypothesized to physically repulse cells from surfaces. Increased and specific production of HA has been recorded during events such as cell migration, cell proliferation, and tumor metastasis, which indicate HA may play a critical role in increasing cell motility. The primary objective of this work is to quantify the physical influence of HA polymers on cell adhesion strength. Using a hydrodynamic spinning disc assay, average cell adhesion strength will be quantified for various cell types, including rat chondrocytes and prostate cancer cells, in both the presence and absence HA. A more comprehensive understanding of factors influencing cell adhesion dynamics may elucidate targets for new therapeutic approaches for diseases such as cancer. The results of this study demonstrate that following HA removal, cell adhesion strength increases, and FA area does not significantly increase. This demonstrates that HA does play a significant role in influencing cell adhesion strength in both physiological and pathophysiological systems. Therefore, HA may be a potent target for future therapeutics in diseases that involve cell adhesion dysregulation.