Current Fellows

Chris Bartel Graham Gordon Emily Pipan
Gabby Bates Elyse Johnson John Porter
Anna Burcham Chelsea Leander Hilary Rizk
Blakely Bussie Ethan McCurdy Alex Román
Will Campbell Adam Milton Grace Thaxton
Patrick Donnan  Alysa Moore Abby Threet
Sara Geonczy Madeline Moore J. Alyssa White

Chris Bartel

Project Title: Characterizing the Effect of Macromolecular Comfort Agent Release on Protein Deposition to Silicone Hydrogel Contact Lenses

Mentor: Dr. Mark Byrne, Chemical Engineering

Project Summary: The primary research objective is to engineer a therapeutic contact lens to controllably release comfort molecules thereby developing a technology with the potential to limit the discomfort felt during lens wear. An additional benefit is reducing protein and lipid deposition to the lens, leading to a healthier lens and a healthier eye.

Abstract: An estimated 60 – 80% of contact lens wearers experience significant discomfort due to dryness and protein deposition to the surface of the lens. Macromolecular comfort agents can be formulated into contact lenses to relieve dryness and limit protein and lipid adsorption. The presence of proteins on the lens surface makes the lens feel dirty and reduces the wettability of the lens, also resulting in sensations of dryness. The permanent sequester of comfort agent within a contact lens structure has been shown to reduce the rate of protein deposition to the surface of a typical hydrogel contact lens. Recently, our group has demonstrated the controlled, continuous release of macromolecular comfort agent from a silicone hydrogel contact lens for up to 60 days. However, the effect of comfort agent release from a silicone hydrogel contact lens—the most prevalent lens material today—on protein deposition has not been explored to date. The effect of macromolecular comfort agent release on protein deposition will be characterized both quantitatively and qualitatively. The rate of protein deposition to a novel silicone hydrogel contact lens material will be analyzed at various levels of comfort agent release in an attempt to find an optimal release rate of comfort agent such that protein deposition to the lens surface is effectively minimized. The lens surface will also be characterized using microscopy and hydrophobic sensitive dyes to assess the effects of comfort agent release and protein deposition on the lens surface morphology.

 

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Gabby Bates

Project Title: The Common Thread in Important Literary Journalism

Mentor: Dr. Margaret Marshall, English

Project Summary: This project attempts to discern which features the most culturally significant works of literary journalism have in common by conducting a rhetorical analysis of four New Yorker articles published in the post-WWII era on behalf of victims of injustice. Findings will be compiled in a critical article to expand knowledge of the creative nonfiction genre.

Abstract: In light of the current dearth of scholarship on the genre of creative nonfiction writing, this project attempts to discern and interpret rhetorical commonalities among the most important works of literary journalism ever published. “Hiroshima” by John Hersey, “Silent Spring” by Rachel Carson, “A Letter from a Region in my Mind” by James Baldwin, and “That Was Pugilism: The White Hopes” by John Lardner—all published in The New Yorker during the post WWII era— will be used as subjects for analysis. The immense cultural sway of The New Yorker in the 40s, 50s, and 60s, combined with the enduring fame and real-world implications of the works on American society, establish these four titles as examples of the most highly influential creative nonfiction ever published. The rhetorical analysis of these works will borrow from the rhetoric of inquiry theory exemplified in such critical essays as James Boyd White’s “Human Dignity and the Claim of Meaning: Athenian Tragic Drama and Supreme Court Opinions.” This method—which draws parallels between specific textual instances, places each in its respective context, and interprets the effects of stylistic choices on the audience— will conclude in a critical article in which the determined parallels are rephrased into questions that can be applied to encourage analysis of other creative nonfiction texts and more informed crafting of literary journalism in the future.

 

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Anna Burcham

Project Title: Development of Targeted Nanomedicines for Treatment of Prostate and Breast Cancers

Mentor: Dr. Robert Arnold, Pharmacal Sciences

Project Summary: Cancer is the second leading cause of morbidity and mortality in the US.  Chemotherapy is effective, but can lead to toxicity in other areas of the body other than the tumor. The goal of my research is to exploit differences in cancer cells to develop drug carriers that will increase toxicity at the site of the tumor and limit toxicity in other areas.

Abstract: Cancer is the second leading cause of morbidity and mortality in the US.  Chemotherapy is a useful treatment, but can lead to off-target toxicity. Many chemotherapies used to treat patients fail to achieve optimal drug exposures. Nanomedicines have the ability to alter drug circulation half-life, tissue/tumor distribution and improve antitumor efficacy. Lipid-based nanoparticulate drug carriers, specifically sterically-stabilized liposome (SSL) carriers, have been approved for clinical use, however, their use has been limited because specific mechanisms to control drug release are needed. Secretory phospholipases (sPLA₂), lipid-metabolizing enzymes, are upregulated in prostate and a variety of other solid cancers. We hypothesize that liposome carriers engineered with lipids sensitive to sPLA2 could be used to control the rate and extent of drug release.  Recently our laboratory created prototype sPLA₂ Responsive Liposomes (SPRL) formulations that modulated drug release and improved drug efficacy in a mouse xenograft model of human prostate cancer compared to existing SSL formulations. In evaluating these formulations, the lab identified a previously unreported finding that phospholipase A2 receptor (PLA2R) is present in prostate cancers and may play an important role in modulating intercellular delivery of lipid nanoparticles.  PLA2R is a membrane receptor that is expressed in cancers and regions of inflammation, and transports sPLA₂ from the interstitial space into cells. It has been shown that there are distinct recognition sites on PLA2R for sPLA2.  Several peptide motifs have been published that interact with high affinity to the specific binding pocket of the PLA2 receptor. We hypothesize that targeting SPRL, with peptide recognition sequences for PLA2R, will enhance internalization of lipid-nanoparticles into cancer cells, increasing drug delivery and antitumor efficacy.

 

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Blakely Bussie

Project Title: The Quantification of Mitochondrial Location and Morphology Using MATLAB

Mentor:Dr. Elizabeth Lipke, Chemical Engineering

Project Summary:

Abstract: The analysis and quantification of biological images is essential for researchers in many disciplines. For proper statistical analysis and results justification, hundreds of cells frequently have to be analyzed by manual counting due to the limitations of image processing tools. In order to better understand the function of human cells and tissues and to be able to use that knowledge to both prevent and treat disease, we need to be able to quantify visual information contained in biological images accurately in a time-efficient, reproducible, and unbiased manner. 

A MATLAB program was created to analyze fluorescently labeled organelles within cells. Specifically, the program was used to locate and quantify mitochondria and nuclei of different cell types, including human induced pluripotent stem cells (hiPSC), human embryonic kidney cells (HEK-293), and a human breast cancer cell line (MCF-7). The program extracts information about the number of mitochondria within the cell, as well as location of the mitochondria relative to the nucleus. Information about the morphology of the mitochondria, such as shape and connectivity was also determined. Compared with manual interpretation, it was found that the MATLAB program was quicker, more consistent, and bias-free. When applied to differentiating stem cells, this program can reveal how the organization and morphology of mitochondria changes with cell maturation and differentiation.

 

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Will Campbell

Project Title: Determination of Mechanical Properties of Articular Cartilage

Mentor: Dr. Robert Jackson, Mechanical Engineering

Project Summary: Healthy articular cartilage is essential for normal joint function because it provides a gliding surface between joint surfaces capable of sustaining stresses and forces. In this study, we will be performing indentation tests on equine articular cartilage to determine some very important and fundamental mechanical properties of the complex biological tissue.

Abstract: After decades of research and dozens of proposed models, the mechanical properties of articular cartilage are still not comprehensively understood. Cartilage is biphasic material, meaning that part of the cartilage is comprised of a solid matrix while the other portion consists of a fluid that is suspended in the matrix. In this experiment, Indentation tests will be performed on the articular cartilage of four different equine joints, all of which are different joint types. Readings from these tests will give insight into the aggregate properties of the cartilage, how the solid and fluid behave together, and the properties of the solid matrix alone. Comparisons of cartilage mechanical properties will then be made between each joint to look for any significant difference that may be associated with the different joint types. We will also examine the difference between freshly harvested cartilage samples, and samples that have been frozen for 7 days. Once these properties have been determined, we can make comparisons between the fresh and frozen cartilage samples to determine if the freezing process causes any significant change to the cartilage properties.

 

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Patrick Donnan

Project Title: Polariton Band Structure Calculations

Mentor: Dr. Jianjun Dong, Physics

Project Summary: Our goal is to develop a new theory of heat conduction at high temperatures. In particular, a newly proposed hypothesis of diffusive heat transfer carried by infrared (IR) phonon-polaritons will be the main focus of our research. We will study silicate pervoskite (MgSiO3) and magnesium oxide (MgO), the two most abundant minerals in the Earth’s lower mantle.

Abstract: Understanding the thermal conduction properties of solids is a main focus of solid-state physics research, due to its importance for both technological applications, such as in electronics that must function over a wide range of temperatures, and geophysical applications, such as of studying mineral thermal conductivity under extreme pressures and temperatures in the Earth. Our research is focused on studying the corrections to the conventional phonon gas model at high temperatures caused by the strong coupling between infrared (IR) photons (quantum light particles) and IR phonons (quantized lattice vibrations). Current theory treats photons and phonons as independent heat carriers, with photons contributing to ballistic heat radiation and phonons contributing to diffusive heat conduction, and only approximates the photon-phonon interactions in terms of dielectric constants and photon absorption coefficients. However, such approximations likely breakdown at extremely high T, such as those deep in the Earth, because the strong phonon-photon interaction will lead to the formation of new quantum quasi-particles called IR-polaritons. In our study, we will perform first-principles calculations of the energy band structure for IR-polaritons, and develop a kinetic transport model to evaluate the contributions of IR-polairtons to heat conductivity at high T. We plan to study silicate pervoskite (MgSiO3) and magnesium oxide (MgO), the two most abundant minerals in the Earth’s lower mantle.

 

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Sara Geonczy

Project Title: Private Waste and Public Costs: Economic Analysis of Effective Policies for Municipal Solid Waste Management

Mentor: Dr. Yaoqi Zhang, Forestry and Wildlife Sciences

Project Summary: The purpose of this research project is to analyze the decomposition of the total cost of municipal waste disposal services in order to investigate different price structures and other policies that will more appropriately allocate costs, minimize costly waste disposal activities, increase positive waste disposal activities, and maximize total social welfare.

Abstract: According to the EPA, the United States handles its trash primarily in three ways: landfilling, recovery (recycling), and incineration. Municipal Solid Waste (MSW), Construction and Demolition waste, and Industrial Waste generated in Lee County, along with 21 other counties in both Alabama and Georgia, are sent to the Salem Waste Disposal Center in Salem, Alabama. Alabama has relatively low tipping fees (price per ton for waste disposed in a landfill) and low rates of resource recovery which may be a result of a systemic failure in the economics of waste disposal. The City of Auburn manages public waste disposal services that incur pecuniary and externality costs for collection, hauling, and landfill disposal. In Auburn, as in many other municipalities, household waste disposal fees are generally the same for each household regardless of the amount and type of waste generated. This leads to a classical free-rider problem commonly studied in environmental and ecological economics. The purpose of this research project is to analyze the decomposition of the total cost of waste disposal services for the municipality of study, the city of Auburn. Total cost includes both pecuniary costs and externalities, which are based on public records, interviews, and extensive literature review. Once the total cost has been itemized, the project will investigate how these costs are passed on to the users of the service. A comparison of different price structures and other kinds of policies, with respect to the costs that each policy will incur for implementation, determines which policy will allocate costs most appropriately, minimize costly waste disposal activities (illegal dumping, recycling contamination, waste tourism), increase positive waste disposal activities (recycling, composting, waste minimization), and maximize total social welfare. This objective policy study will be supplemented by survey responses in order to gauge customer responsiveness and thus success of each suggested policy. This research project can serve as a case study to be referred to by other municipalities.

 

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Graham Gordon

Project Title: Vectorization of Spring Network Equilibrium Algorithm for Euclidean Distance Matrix Completion

Mentor: Dr. Peter Nylen, Mathematics and Statistics

Project Summary: Trying to determine the locations of a collection of points knowing only the distances between some of the points is known as the Euclidean Distance Matrix Completion Problem (EDMCP). Our project seeks to improve an existing algorithm which finds approximate solutions to the EDMCP. Applications include molecular conformation and sensor network localization.

Abstract: Euclidean Distance Matrices (EDMs) are real, symmetric, n-by-n matrices whose (i,j) entry is the squared Euclidean distance between the points i and j, given a set of n points. Partial EDMs are real, symmetric matrices with zeros on the main diagonal and non-negative entries but which have some entries unspecified. The EDM Completion Problem (EDMCP) is to fill in the unspecified entries such that the resulting matrix is an EDM. The purpose of this research is to improve the run-time of a program which finds EDMs that are close to completions of given partial EDMs in a minimum energy sense. The program interprets specified entries of the partial EDM as the squared rest lengths of springs connecting an array of nodes and numerically equilibrates the system such that the sum of magnitudes of forces at the nodes is zero. Unspecified entries represent disconnected nodes. The current approach is to individually equilibrate the nodes, treating connected nodes as momentarily stationary. We seek an algorithm which differs numerically and dynamically from this approach. The goal is a vectorized algorithm which improves efficiency and allows all nodes to move simultaneously. The conjugate gradient method and modified Newton method are to be considered. The EDMCP is of growing interest, as efficient algorithms of the sort have applications including molecular conformation and sensor network localization. Modern problems in these areas may require thousands of distances to be computed. There also exists theoretical relevance to the real positive semidefinite completion problem.

 

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Elyse Johnson

Project Title: Characterizing SlCRF5, a Transcription Factor in Tomato Involved in Stress Response

Mentor: Dr. Aaron Rashotte, Biological Sciences

Project Summary: The aim of my research is to characterize the tomato transcription factor protein SlCRF5, which is responsive to cytokinin, a plant hormone linked to stress response. This knowledge is crucial in understanding the role of SlCRF5 stress response in tomato, and at a broader level, the role of this class of transcription factors in other flowering plants. Application of this knowledge may lead to increased crop yield.

Abstract: Cytokinin Response Factors are a monophyletic group of AP2/ERF family transcription factor proteins present in all land plant lineages. The CRF subfamily has been best characterized in Arabidopsis and tomato (Solanum lycopersicum) which have 12 and 11 CRF proteins respectively. Some CRFs, including AtCRF6, are transcriptionally induced by cytokinin. We have shown that in Arabidopsis leaves, induction of AtCRF6 occurs via the two-component cytokinin signaling pathway and is primarily dependent upon the cytokinin receptor AHK3. Similar to ahk3 mutants, crf6 mutant leaves demonstrate a reduced sensitivity to the senescence delaying effect of cytokinin in a dark-induced senescence assay. Leaves constitutively over-expressing AtCRF6 display delayed senescence in this assay even in the absence of cytokinin. Thus CRF6 appears to act downstream of AHK3, partially mediating the delay of leaf senescence which occurs in response to cytokinin. Additionally, our expression analyses along with available microarray data indicate that AtCRF6 is induced in response to a wide range of stress conditions. This may suggest that AtCRF6 functions as an antagonist toward stress-induced senescence. More recently we have begun to characterize the cytokinin/senescence regulation of the tomato ortholog of AtCRF6, SlCRF5. The preliminary objective of this research is to identify the downstream transcriptional targets of SlCRF5; determining the specific DNA binding sequence recognized by the transcription factor is an essential part of understanding the role of SlCRF5 in the process of senescence.

 

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Chelsea Leander

Project Title: Protein-Energy Malnutrition in Nepal

Mentor: Dr. Katie Thornton, Human Sciences

Project Summary: The first 1000 days of life, beginning at conception, contain crucial and determining factors, including the development of the brain. A child is setback for life when the brain cannot attain full development during this period, often as a result of malnutrition. My research aims to examine the lifestyle of populations who struggle with intergenerational cycles of Protein-Energy Malnutrition, with the ultimate goals of breaking these cycles and enhancing early child development.

Abstract: Protein-Energy Malnutrition (PEM) hinders the body from maintaining, building, and repairing itself. Hence, PEM is life threatening for the mother during pregnancy and the child’s first 1000 days. Research of PEM will be largely concentrated in Nepal where its effects are unquestionably high. Internal and external factors will be evaluated before embarking into a field study component of the research that will take place in Nepal. The field study will provide hands-on assessments of the effects from PEM, which include stunting, wasting, and maternal deaths.  The purpose of this study is to pinpoint root causes behind statistically high percentages of PEM found in specific people groups located in the Himalaya Mountains. Results from this research may aid in breaking intergenerational cycles of PEM and ultimately enhancing child development in the first 1000 days.

 

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Ethan McCurdy

Project Title: The Contribution of Off-mechanism Electron Transfers in the Inactivation of Mycobacterium tuberculosis Catalase-Peroxidase

Mentor: Dr. Douglas Goodwin, Chemistry and Biochemistry

Project Summary: One crucial facet of the immune response is to generate peroxides to rid the body of invaders.  Many bacteria, including M. tuberculosis, depend on an enzyme known as KatG to convert these peroxides into harmless products.  I am investigating the mechanisms that keep KatG in its most active and efficient state.  This holds striking implications for understanding the strategies pathogens use to thwart a host immune response.

Abstract: As the name implies, catalase-peroxidase (KatG) enzymes overcome the threat of hydrogen-peroxide by means of two mechanisms: catalase and peroxidase. The KatG active site contains heme and a novel tryptophan-tyrosine-methionine covalent adduct, both of which are essential for the enzyme’s catalase activity. In contrast, the peroxidase activity only requires the heme, not the adduct.  The mechanism by which hydrogen peroxide is decomposed by KatG is yet to be fully understood. Some have asserted that catalase and peroxidase activities should mutually exclude each other by nature of their mechanisms.  However, we argue that these activities are not exclusive and our experiments have shown that peroxidatic electron donors such as tetramethyl benzidine substantially stimulate catalase activity.  Accordingly, this project seeks to understand how peroxidase activity influences catalase activity. The electron donors most effective in stimulating catalase activity are too large to have direct access to the heme edge for electron transfer, so to further understand the synergistic contribution of these compounds, it becomes essential to determine the routes by which electrons are transferred from the protein surface to the buried active site.  Among other candidates, I have begun evaluating tryptophan 438 due to its proximity to arginine 418, which has been observed to undergo a conformational change that corresponds with the greatest stimulatory effect of the electron donors. Due to its position and oxidizability, tryptophan 438 is a likely candidate to participate in an electron-transfer conduit. For similar reasons, tyrosine 113 is also under investigation. We anticipate that a greater understanding of the role of peroxidatic electron donors in the mechanisms of KatG-dependent hydrogen peroxide decomposition will shed light on the use of this enzyme by pathogenic organisms to side-step host immune responses. Further, these studies may lead to strategies to exploit KatG as a target for novel antibacterial agents.

 

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Adam Milton

Project Title: “Smart” Nanocomposite for Enhanced Drug Delivery of Insulin

Mentor: Dr. Allan E. David, Chemical Engineering

Project Summary: A drug delivery system capable of delivering reliable and consistent doses of insulin through the oral route would provide significant advantages over the commonly used insulin pumps and injections. In order to enable a less invasive route of administration, I plan to engineer a drug delivery vehicle, in this case comprised of a nanocomposite, that can protect insulin from degradation and control its release in the body for an extended period of time. A “smart” nanocomposite composed of silica and chitosan, to regulate insulin release, will be utilized to achieve this goal.

Abstract: Recent proliferation of diabetes requires a smarter delivery system for insulin to pass into the bloodstream. Currently, 7% or 20.8 million Americans suffer from type I or type II diabetes. As a result, many people could benefit from a more convenient drug delivery system. Insulin most commonly is delivered through subcutaneous systems, such as a pump or injection, directly into the bloodstream. These systems, however, are extremely invasive; lowering patient compliance with insulin regiments, especially in pediatric patients. Therefore, delivering insulin through an oral route becomes a convenient and desired solution to this problem. Administering insulin through the GI tract, however, has its own problems. Insulin is degraded by the proteolytic enzymes in the GI tract and is unable to cross the intestinal mucosal lining – which is a barrier that must be navigated to enter the blood stream. For this reason, a nanocomposite delivery vehicle composed of silica and chitosan is proposed to increase the uptake of insulin in the bloodstream when it is administered orally. The proposed pH-responsive nanocomposite is designed to swell at a predetermined pH in order to control release of insulin within a particular zone of the GI tract (e.g. stomach or intestine). Chitosan has been noted for its ability to adhere and interact with tissue surfaces in the stomach and intestine ultimately furthering the insulin’s ability to reach the bloodstream.  Investigation of chitosan and other biopolymers for mucoadhesive properties will be done in order to increase the bioavailability of insulin. Furthermore, engineering a nanocomposite drug delivery system, as proposed, spearheads a movement toward higher patient compliance by improving the oral bioavailability of medications that are not traditionally administered orally.

 


Alysa Moore

Project Title: Biochemical and Genetic Characterization of an Unknown Anti-Nematode Compound

Mentor: Dr. Mark Liles, Biological Sciences

Project Summary: My research focuses on identifying and characterizing an unknown compound produced by a bacteria commonly used in industrial agriculture for its anti-nematode abilities. Once the compound has been identified with biochemical methods, I will analyze the bacteria’s genome in order to evaluate environmental conditions that cause the compound to be produced in greater abundance, which could thereby increase anti-nematode activity. Greater understanding of this compound could provide a more sustainable alternative to other common, less environmentally-friendly soil additives.

Abstract:  Field testing of Bacillus firmus strain GB-126 has clearly indicated that this strain is producing some unknown compound which causes a decrease in nematode presence in the soil. A bioassay has been developed to test fractions of GB-126 supernatant for anti-nematode activity in order to isolate the desired compound. The bioassay will be adapted for laboratory use with model organism Caenorhabditis elegans, which will allow faster testing than when utilizing plant pathogenic nematodes. It has been previously determined that the un-fractionated GB-126 supernatant has the ability to kill nematodes. Upon isolation, mass spectrometry and X-ray crystallography will be utilized to elucidate the structure of the compound. Along with the aforementioned objectives, the research will also investigate the nature and significance of the gene(s) necessary for nematode control by GB-126. Genome sequence analysis will be utilized to determine how the genes predicted to be responsible for anti-nematode activity are similar to those of other bacteria and further work will be done to construct a mutant in the identified biosynthesis pathway in order to test its significance in biological control.  Identification of the genes that are necessary to produce an anti-nematode compound will allow me to then test for expression of these genes when the GB-126 is grown under different conditions, such as in the presence of a plant root, nematodes, or different medium additives. These studies will help increase understanding of the mechanism of action for GB-126 biological control of nematodes and can result in improved efficacy in field application of this sustainable biological alternative to chemical treatments for pest control.

 

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Madeline Moore

Project Title:Growth Characteristics of Xylella fastidiosa in Media Modified to Mimic Xylem Fluid

Mentor: Dr. Leonardo De La Fuente, Entomology and Plant Pathology

Project Summary:  Xylella fastidiosa (Xf) is a bacterial plant pathogen that infects numerous plant species in the United States. The bacterium forms biofilms inside the water-conducting xylem vessels of the plants, therefore obstructing water movement. The aim of my research is to develop a defined culture media for research in the laboratory, in which Xf will grow and form biofilm in a similar manner to its natural setting inside plants.

AbstractXylella fastidiosa (Xf) is a bacterial plant pathogen that infects the xylem of numerous economically important plant species in the United States including grape, peach, almond, pecan, and blueberry. Symptoms caused by Xf are believed to be the result of Xf-induced plugging of the xylem vessels which transport water and nutrients to the plant. This plugging is believed to be caused by the formation of biofilm, which consists of dense aggregates of Xf cells and other compounds. Due to its fastidious nature, certain media for growing Xf have been developed that are not successful at reproducing the natural conditions for this bacterium. PD2 is the most commonly used media for research on this bacterium. Another possible media that has been explored for the growth of Xf is grapevine sap. When grown in sap, Xf has been observed to grow more quickly and form a denser biofilm. Comparison of the grapevine sap and PD2 media reveals differences between the mineral compositions. The aim of my research is to account for these differences and supplement the PD2 media so that Xf will grow more similarly to how it grows in its natural setting. Once a new media has been defined, microfluidic chambers can be used to compare the growth, movement, and biofilm formation of Xf. The definition of a media that reproduces natural growth conditions for this bacterium is important because it will allow for a better understanding of the infection process inside the plants.

 

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Emily Pipan

Project Title: On-line LC-MS Based Identification of Inhibitors of the Mycobacterium tuberculosis Shikimate Kinase

Mentor: Dr. Angela Calderón, Pharmacal Sciences

Project Summary: The goal of my research is to use liquid chromatography-mass spectrometry (LC-MS), a sensitive mass-measuring process, to find inhibitors of the enzyme shikimate kinase. This enzyme is from the bacterium Mycobacterium tuberculosis, the pathogen that causes tuberculosis. Inhibition of the enzyme would severely harm the cell's normal processes, representing the first stage in new drug discovery.

Abstract: Mycobacterium tuberculosis is a highly virulent pathogen responsible for a staggering number of infections and deaths every year. This, in combination with the rapid emergence of multidrug resistant (MDR) and extremely drug resistant (XDR) strains, makes M. tuberculosis one of the gravest threats to the health of the global human community. 

This research is centered on a specific enzyme of M. tuberculosis shikimate kinase (SK). This enzyme is an ideal target for development of new antibiotics because the shikimate pathway is not found in the human metabolism but is essential for the survival of M. tuberculosis. The objective of this research is to identify compounds that would likely be good drug candidates to treat M. tuberculosis. The main hypothesis of this project is that compounds which specifically interfere with the MtSK mechanism would most likely be explicitly inhibitors of MtSK. This reduces the likelihood of side effects in mammal specimens. The research strategy involves testing a variety of natural products and plant and marine extracts for MtSK binding affinity and enzymatic inhibition. 

The first aim is to develop an on-line liquid chromatography-mass spectrometry (LC-MS) based method to more rapidly identify MtSK inhibitors and validate this system with known MtSK inhibitors. His-tagged MtSK will be immobilized to a Ni^(2+)-based support via immobilized metal affinity chromatography (IMAC) and become the basis for the on-line LC-MS method. This system will evaluate natural product mixtures based on their affinity for immobilized MtSK and then evaluate the degree of inhibition by mass spectrometry. Twenty-six candidates were previously screened for MtSK inhibition using an off-line enzyme inhibitory assay. These prior results will provide positive and negative standards for validation of this more efficient method. The second aim is to isolate and identify natural products that are likely to be effective MtSK inhibitors from plant and marine extracts. Nuclear Magnetic Resonance (NMR) will be used as a complementary technique to identify and validate identified inhibitors.

 

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John Porter

Project Title: Electrically Conductive Polycaprolactone Nanostructures for cardiomyocyte differentiation

Mentor: Elizabeth Lipke, Chemical Engineering

Project Summary: The goal of my research is to create an electrically conductive substrate on which to grow cells. The intent is to find a reliable method for growing cardiac tissue with the end goal being able to influence the differentiation of stem cells into cardiomyocytes.

Abstract: In the United States, heart disease is the leading cause of death for both men and women, taking over 616,000 lives in 2008. Additionally, over 250,000 people in the U.S. have spinal cord injuries (SCIs). Most new SCIs occur in Americans between ages 16-30, resulting in lifelong disabilities. There are currently no clinical methods to reverse heart or spinal cord damage. Re-generating damaged tissue in the heart and brain will require that we can expand replacement cells outside the body. In an effort to achieve this goal, research is being conducted on nanowires that can be used to effectively grow viable cells without the need of additional chemical components. The current hypothesis is that by designing and fabricating nanowires that are conductive, the nanowires will be more conducive to the growth and differentiation of cells, especially those of the heart and brain, which have intrinsic electrical activity. 

In order to create such a nanostructure, polycaprolactone and a nanostructured template will be employed. The polymer will be pulled into the pore structure of the template, which is later leached away using sodium hydroxide. Some of the nanostructured polymer samples will be treated with polypyrrole in order to make them conductive. The rest of the samples will be left as non-conductive controls.  The growth of cardiomyocytes seeded onto the different nanowires will then be characterized using microscopy and optical mapping. 

Better understanding of the interface between cells and biomaterials, including the electrically active polymers under investigation, is an essential step in the process of forming better electrical interfaces between the body and prosthetic devices.

 

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Hilary Rizk

Project Title: Validation of Detection Methods for Assessing the Exposure of Haemorhous mexicanus to the bacterial pathogen Mycoplasma gallisepticum

Mentor: Dr. Geoffrey Hill, Biological Sciences

Project Summary: Development of accurate methods for detection of bacterial pathogens in birds is important in decreasing the costs of research and saving the lives of birds. The goal of my research is to validate the use of throat swabs and blood tests in detection of exposure of birds to a bacterial pathogen. By validating the accuracy of these tests, my research will improve the accuracy and efficiency of further research of bacterial pathogens and birds.

Abstract: Within the past two decades the house finch (Carpodacus mexicanus) has become the host of a pathogenic bacterium Mycoplasma gallisepticum (MG). In 1994, this species of bacteria moved from domestic chickens (Gallus gallus) to house finches. The introduced pathogen spread quickly throughout house finch populations in the Eastern United States and is estimated to have killed around 100 million birds. When doing research on the evolution and pathogenicity of MG in house finches it is important to have an accurate method for detection of exposure to the pathogen in the birds. This study will test for exposure to MG using three different methods. These methods are testing for bacterial DNA on a throat swab from the bird, testing for antibodies for the pathogen in a blood sample from the bird, and also testing tracheal tissue from the bird for the presence of MG DNA. While the first two methods are widely used, it is tracheal tissue that is currently thought to give the most accurate results. Through my research I will be performing a study to validate the use of throat swabs and antibody analyses in the detection of exposure of house finches to MG. This study will answer the question of whether throat swabs and antibody analyses are reliable tests for the presence of MG in house finches.

 

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Alex Román

Project Title: The Use of Subcritical Water to Convert Sunn Hemp Biomass into a Value Added Product

Mentor: Dr. Ram Gupta, Chemical Engineering

Project Summary: This project aims to combine the promising protein content of sunn hemp with a subcritical water extraction method, and then optimize it for industrial use. This new extraction method would eliminate toxic solvents needed, reduce transportation cost moving the biomass to/from a refinery, and provide the farmer with readily eaten fodder for domesticated ungulates (goats, pigs, etc).

Abstract: Recent strides in medical technology have opened new avenues of understanding the complexities of thought processing and memory in the human brain. EEG and MRI are two simple tools that have let to new ways of simplifying and modeling the brain. Using neural networking techniques, statistics and electrical activity as primary elements in simulations, these predictive models have allowed researchers to understand the effect of stimuli within the brain and the physical process of how we think. Biology, biochemistry, neuroscience, and psychology (to a certain extent) have been able to verify to the legitimacy of these models but have yet to be accounted for explicitly with the process models themselves.

Neurons, like all cells, receive a majority of their energy in the form of chemical energy from compounds like glucose. However, when the cell metabolizes these compounds not all of the potential energy is converted into energy vital for the cell to live, but all of the energy is conserved. Some of the chemical energy is combined with the fluctuating electrical energy from other neurons and as a result cause a flow of energy through the brain. Using the Laws of Thermodynamics, this system can be modeled in a neural network to determine why electrical and physical signals are more inclined to “light up” a specific area of the brain.

This project aims to first model these phenomena by incorporating thermodynamics into neural network elements and mathematically deriving a physical relationship in the brain. This will be accomplished through the development of a functional system response algorithm and simulating the results on a 2-D scaffold of the brain in MATLAB. After the model has been created, it will be verified through the application of sensory input. The goal is to be able to replicate previously gathered fMRI data in real time and use the model as a new predictive tool in neuroscience. Future applications of this model could include new understandings in how people learn and transfer information.

 

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Gracie Thaxton

Project Title:  Sequence Comparison of ArkDPI-derived IBV Vaccine Genome Before and After Adaptation to Culture

Mentor: Dr. Vicky van Santen and Dr. Haroldo Toro, Veterinary Pathobiology

Project Summary:  Avian infectious bronchitis virus (IBV) is a respiratory virus of chickens belonging to the same virus family as human SARS and MERS viruses. To aid understanding of what changes in coronaviruses allow them to adapt to different host systems, we will adapt IBV vaccine to chick kidney cells. I will sequence the viral genome before and after adaptation.

Abstract:  The avian coronavirus infectious bronchitis virus (IBV) causes an economically important respiratory disease in broiler chickens. Control is through vaccination, but is difficult due to the frequent emergence of new serotypes. Furthermore, in spite of intensive Ark-DPI vaccination, Ark-DPI-type IBV is the most frequently isolated IBV type in the major broiler producing regions of the U.S.. We previously characterized the genomes of Ark-DPI-derived live-attenuated vaccines and found that they contained multiple subpopulations, some of which are rapidly selected during a single passage in chickens. The portion of the viral spike (S) gene encoding the protein responsible for attachment to host cells (S1 subunit) of the vaccine subpopulations selected in chickens is similar to the virulent Ark-DPI isolate, suggesting that the selected subpopulations represent residual virulent Ark-DPI persisting in the attenuated vaccines. Analysis of the entire vaccine genomes also indicates vaccine subpopulations similar to the virulent Ark-DPI outside of the S gene. IBV isolates that have been adapted to chicken embryos, as attenuated vaccine strains have been, can be adapted to cultured chick kidney cells. To examine the IBV genome changes associated with adaptation to chick embryo kidney cells, we will adapt an Ark-DPI vaccine strain to chick embryo kidney cells and conduct deep sequencing analysis of the vaccine population before and after adaptation. Understanding what portions of the genome change to allow survival of the virus in cell culture will give us insight pertaining to the fitness of the virus in different host systems and how it changes in response to the selective pressures of cell culture. Because we will use a different vaccine lot than previously analyzed, we will also be able to address lot-to-lot variation in vaccine subpopulation structure.  
Human coronaviruses sudden acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) viruses are thought to have emerged from animal hosts. Our work is relevant to how coronaviruses adapt to different host systems.

 

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Abby Threet

Project Title: Mitochondrial Copper Transport: Investigating Genetic Interactions with PIC2

Mentor: Dr. Paul A. Cobine, Biological Sciences

Project Summary: Copper is required for human life. This element is a cofactor for the protein cytochrome c oxidase (COX), which is required for respiration. The pathway for copper transport into mitochondria, the location of COX, is essentially unknown. My fellowship will allow me to study genetic interactions in baker’s yeast in hopes of shedding light on this pathway. This research will contribute to understanding an essential process and will translate to understanding disorders of copper metabolism in humans.

Abstract: Copper is required in mitochondria for activity and stability of cytochrome c oxidase (COX) in the inner membrane and superoxide dismutase in the intermembrane space.  Activity of COX is essential for yeast to grow on non-fermentable carbon sources and Sod1 protects cells against radical induced damage by removing reactive oxygen species.  The copper provided to these proteins comes from a soluble pool found in the matrix.  This pool of copper is chelated by a non-proteinaceous, fluorescent ligand (CuL).  Biochemical depletion of CuL leads to respiratory defect in Saccharomyces cerevisiae as a result of decreased COX activity. The current model for mitochondrial copper homeostasis suggests CuL complex formed in the cytosol crosses the outer membrane and then enters the matrix before redistribution to the intermemrbane space. The mitochondrial inner membrane is impermeable, preventing free diffusion of the CuL complex. We identified the mitochondrial carrier family protein Pic2, as a transporter of copper into the mitochondrial matrix. However we have not identified the export protein/s or the accessory proteins that assist Pic2 in import. My fellowship will focus on identifying the other proteins in this pathway using Saccharomyces cerevisiae as a model using synthetic genetic array screening for phenotypes induced by the copper competitor silver. We expect to find CuL biosynthesis and transporters of copper in mitochondria.

 

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J. Alyssa White

Project Title: Amassing Evidence: A Study of Body Mass Variation in the Robert J. Terry Skeletal Collection

Mentor: Dr. Kristrina Shuler, Sociology, Anthropology, and Social Work

Project Summary: I intend to study the Robert J. Terry Anatomical Skeletal Collection housed at the Smithsonian Institution. My work will complement that of a team of specialists and contribute a vital component through analyses of bone’s reactions to body mass and activity. This is an extension of the body size research that I have been pursuing for a few years, which I hope will improve understandings of the effects of body mass on the skeletal tissue in past and modern populations.    

Abstract: The politics and power of a society can write themselves on the bodies of its citizens. Moreover, labor and activity throughout a lifespan leave their effects on a person’s body, which can be used as evidence in the future for those societal trends. In biological anthropology especially, bones can be used to analyze health, stress, trauma, disease, and so forth in individuals and populations from the past. Bone is a dynamic tissue that responds to the stress placed upon it, as traditionally stated in Wolff’s Law. Recently, the exploration of entheses (“musculoskeletal stress markers”) has gained great attention in anthropological literature. Entheseal markers can be used to determine activity during a lifetime, but their anatomical variation remains poorly understood. Up until this point, the criteria for analysis of these markers have been very subjective and do not account for variation within or between populations. Research will aim to quantify that variation so that new methodologies can be applied to archaeological settings. The research group I will be a part of will be going to the Smithsonian’s National Museum of Natural History to study the Terry collection, a 20th century cadaveric collection. This work will focus on creating three-dimensional scans of the bone and I would be complimenting their work using linear measurements. The entheses would be examined in relation to the body mass, determined by the femoral head diameter. I will measure twelve different entheseal markers for maximum breadth and length on each individual and then those measures to the body mass. My work would supplement the larger study and play an important role in determining the role of overall body mass in relation to markers for activity on the bone, as both demand reactions. The methods can later be applied to archaeological collections and help improve the ability to critically analyze the activity patterns of the past and their implications.

 

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Last Updated: October 16, 2013

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