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2013 CURBS Research Symposium October 21, 2013 5:00pm-7:00pm J. Wayne Reitz Union Table of Contents Welcome……………………………………………………………………….…2 Student Abstracts………………………………………………………………3 Faculty Mentors………………………………………………….……………12 Support………………………………………………………………………….13 1 Welcome Welcome to the 1st Annual Center for Undergraduate Research Board of Students (CURBS) Research Symposium! Undergraduate research is one of the five areas of opportunity, along with internships, service, leadership, and international experience that students are encouraged to participate in during their undergraduate career. The mission of the CURBS is to help undergraduates become more involved in the research process, and to improve the student research experience in existing undergraduate programs. We aim to foster a challenging scientific environment in the undergraduate community. This symposium is organized to showcase undergraduate research efforts from across the University of Florida campus. By implementing this symposium in the fall semester, we encourage early involvement in research for students seeking research opportunities, while enhancing presentation experience for student researchers. Each of these student researchers has benefited from mentoring provided by exceptional faculty researchers. We thank them for their efforts on behalf of the undergraduate students. We encourage you to share in this project as you visit the presentations and read the collection of abstracts. Mindy Wang Director, CURBS Research Symposium 2 Parisa Amirzadehasl Faculty Mentor: David Fuller Home institution: University of Florida Research Field: Health-related (Pharmacy, Dentistry, Medicine, Nursing, Physical Therapy, etc.) Effect of Fetal Spinal Cord Tissue and Chondroitinase ABC on Respiratory Function following Cervical Spinal Cord Injury A majority of spinal cord injuries occur in the cervical region. Previous studies by our group has suggested that fetal spinal cord (FSC) tissue survives well after transplantation into the injured spinal cord, but does not integrate well with the host tissue due to glial scarring around the transplant. One barrier to host-graft connectivity is the presence of inhibitory molecules in the scar. In this ongoing study, we are investigating if the combined treatment of Chondroitinase ABC, an enzyme that is capable of breaking down the inhibitory molecules and reducing glial scarring, with FSC transplants will improve respiratory function following a cervical spinal cord injury. Sprague Dawley rats received a C3/C4 hemicontusion injury followed by an intraspinal injection of FSC tissue and Chondrointinase ABC one-month post injury. Breathing was measured at 2 months post-transplantation using plethysmography. Phrenic nerve activity was also assessed under anesthesia. Preliminary data suggest a trend towards a higher tidal volume as well as increased phrenic motor output in rats treated with a transplant and Chondroitinase ABC. These results suggest that coupling FSC transplantation with intraspinal Chondroitinase ABC delivery might lead to improved functional outcomes following spinal cord injury. Justin Arami Faculty Mentor: Alan Katritzky Home institution: University of Florida Research Field: Physical Sciences Synthesis of Energetic 3,5-disubstituted 1,2,4-oxadiazoles Oxadiazole heterocycles are important structural units to drug discovery and the pharmaceutical industry, and have also been studied as corrosion inhibitors as well as building blocks for energetic materials. Oxadiazoles present high densities, good oxygen balance, and high heats of formation, making them a target of interest in the development of explosives with low sensitivities. Though they have been subject to current research, few energetic 1,2,4oxadiaoles have been explored. In an effort to develop new synthetic routes to novel energetic materials, progress is being made to synthesize energetic 3,5disubstituted 1,2,4-oxadiazoles and measure their thermochemical properties and the effects of selected electron withdrawing groups. 3 George Armanious Faculty Mentor: Prabir Barooah Home institution: University of Florida Research Field: Engineering Economic Benefits of Implementing Nighttime Setback Control in Campus Buildings This paper analyzes the economic benefits of implementing nighttime setback control in air handling units (AHUs) in HVAC systems. The AHU studied in this paper is AHU 2 in Pugh Hall, which only services Pugh room 170. A simulation of the room was created using basic thermodynamic laws and estimated parameters from previous studies concerning Pugh Hall. It was found that approximately $8000 could be saved annually if this type of control is implemented. Julie Baniszewski Faculty Mentor: Emma Weeks Home Institution: University of Florida Research Field: Biological Sciences Cold Tolerance: Improving Mass Rearing of Cricotopus lebetis, the Hydrilla Tip Miner The hydrilla midge, Cricotopus lebetis, is a potential biological control agent for the invasive weed hydrilla. Hydrilla was introduced into Florida through the aquarium industry in the 1950s and has since thrived. Hydrilla invades natural ecosystems with surface mats which clog waterways, prevent sunlight penetration and compete with native Florida plants. As a larva, the hydrilla midge mines into the apical meristem of hydrilla preventing further vertical growth and surface mats. The midge is currently being reared in colony for mass release to augment existing populations. Eggs are often held at cold temperatures for storage, to delay development or for transportation to field release sites. Therefore, it is important to understand possible consequences on hatch rates, development or final adult emergence. Eggs masses that had been stored at 5oC for 1, 2, 4, 7, 14, and 21 days were tested for hatch success, larval development to pupation and adult emergence. Hatch success decreased significantly after day 7 of refrigeration. Final adult emergence was significantly affected after only 2 days at 5oC. The knowledge gained from this study will help reduce negative impacts on hatch rates and midge development by reducing storage or compensating with more eggs if storage is necessary. 4 Evan Broggi Faculty Mentor: Alan Katritzky Home Institution: University of Florida Research Field: Physical Sciences Synthesis of C-Terminus Taurine di-, tri- and Tetrapeptides and N-,O-,SConjugates New approach towards water-soluble peptidomimetics that include taurine moiety is described. Taurine, a non-protein sulfur containing amino acid, is the most abundant free amino acid and has been shown to play several essential roles in the human body and considered as an essential nutrient in certain species. In live organisms taurine does not participate in the formation of peptide bonds being deficient of the C-terminal carboxylic group, although, as a part of cytoprotective mechanism, it conjugates with bile acids such as cholic acid, producing taurocholic acid. In this work a series of acylations of taurine at N-terminus allowed synthesis of a number of peptides and conjugated systems. We investigated the reactivity of taurine through its N-terminus protection with Cbz group, SO2OH activation and further acylation of various N-, O-, Snucleophiles using benzotriazole methodology. Analogous methodology is used to incorporate taurine as a C-terminus amino acid into the peptide chain. Thus N-protection of taurine followed by its SO2-activation and further acylation allowed us incorporate taurine into peptide chains as well as bioactive moieties of hormones and medicinal drugs. So far we have synthesized twenty three dim tri-, and tetrapeptides that contain taurine at both C- and N-termini. These tetrapeptides are highly soluble in water and ready to serve as novel drug cargo peptides. Scott Cohen Faculty Mentor: Peggy Borum Home Institution: University of Florida Research Field: Health-related (Pharmacy, Dentistry, Medicine, Nursing, Physical Therapy, etc.) InvestiGator's Carnitine Team The Carnitine Team in the InvestiGators Research Honors Society studies the interrelationships among fuel metabolism, diet, the microbiome, and the metabolome. Our clinical samples are from the University of Florida Research Ketogenic Therapy Program that administers a very high fat and very low carbohydrate diet to treat seizures in children with intractable epilepsy. To study a patient’s metabolome, we prepare plasma and red blood cells from a patient’s blood for mass spectrometric analysis. We will conduct both global metabolomics and targeted metabolomics with a focus on the carnitinome. The piglet is our animal model which allows us to address questions too invasive to be investigated in the human neonate. The tissues and samples that cannot be obtained from a child can be harvested from piglets in our very own Piglet Neonatal Intensive Care Unit (PNICU). Currently, we are studying the developing microbiome and metabolome in a term piglet model in a 1-2 day old piglet and a 9-10 day old piglet. This allows us to define the interactions between the metabolome and microbiome during the early stages of life. These translational experiments are designed to lead to knowledge that will facilitate improved care of pediatric patients with chronic disease. 5 Leanne Dumeny Faculty Mentor: Scott Berceli Home Institution: University of Florida Research Field: Health-related (Pharmacy, Dentistry, Medicine, Nursing, Physical Therapy, etc.) Evaluation of Cell Proliferation in Vein Grafts Using Bromodeoxyuridine (BrdU) Vein grafts are a form of treatment for vascular diseases but often only provide short-term improvement due to the possibility of the grafts failing from intimal hyperplasia and remodeling of the graft. A shearing force across the endothelium leads to proliferation of cells within the vessel and causes biochemical and morphological changes to the graft. In this study, we sought to find a correlation between the rate and timing of cell proliferation with intimal hyperplasia development. In order to find a correlation, vein graft samples were stained for bromodeoxyuridine (BrdU), an immunohistochemical stain used to assess cell proliferation. Vein grafts were performed and harvested 2 hours, 1, 3, 7, 14, and 28 day(s) after implantation in BrdU-injected rabbits and slides were generated for each time point. Positive cells are visibly stained and counted to determine the proliferation rate. Data from each sample will be quantitatively compared and the high flow and low flow graft for each rabbit will also be compared. These data will be used as part of a model to understand the biological and physical effects of the vein graft and the process of vascular adaption from the injury. Jesse Gordon Faculty Mentor: Leslie Murray Home Institution: University of Florida Research Field: Physical Sciences Utilizing a Multi-Nucleating Macrobicyclic Ligand to Selectively Form Dimetallic and Trimetallic Ni(II) and Cu(II) Complexes Multi-electron redox processes involving small molecules (e.g. the reduction of carbon dioxide) are catalyzed by metalloenzymes containing metal clusters that provide redox equivalents for small molecule transformations to occur. Additionally, these metalloenzymes form an internal substrate binding pocket in the active site that implements hydrogen bonding to enforce selective substrate interactions. Murray Group aims to explore the design and reactivity of multimetallic complexes of macrobicyclic ligands in which cluster assembly is controlled by design and a central cavity for substrate binding is incorporated to facilitate these processes. To these ends, a cryptand ligand, featuring a tris(2-ethoxy-3-isopropylphenyl)methane cap bridged by three internally facing pyridinedicarboxamide arms that allows suitable space for substrate binding, has been employed to selectively form dimetallic and trimetallic complexes of Ni(II) and Cu(II). Evidence for synthesis of these complexes is supported by, elemental analysis, X-ray Crystallography, Mass Spectrometry, Infrared Spectroscopy, and Nuclear Magnetic Resonance. These complexes can provide insight into carbon dioxide fixation, metalloenzyme redox mechanisms, and the importance of hydrogen bonding in catalysis. 6 Halie Guelfi Faculty Mentor: Roland Staud Home Institution: University of Florida Research Field: Health-related (Pharmacy, Dentistry, Medicine, Nursing, Physical Therapy, etc.) Predictors of Clinical Pain in Patients with Rheumatoid Arthritis or Fibromyalgia Syndrome Correlations are poor between clinical pain and objective tissue abnormalities in many clinical disorders, including osteoarthritis (OA), rheumatoid arthritis (RA), and fibromyalgia syndrome (FM). Neither joint swelling, articular cartilage loss, nor inflammation predict well the magnitude of symptoms of OA, RA and FM patients. In addition, lack of easily identifiable tissue abnormalities in FM makes these patients pain complaints difficult to understand. However, recent findings of consistent neuroplastic changes in OA, RA, and FM patients suggest common nervous system mechanisms relevant for their clinical pain including peripheral and central sensitization. Thus we hypothesized that testing of peripheral and central pain sensitivity of RA or FM patients will predict their clinical pain better than joint abnormalities, including number of tender and swollen joints. Sadra Hamedzadeh Faculty Mentor: Alan Katritzky Home Institution: University of Florida Research Field: Physical Sciences Pd-promoted Cyclo-dimerization Route to Cyclic Tetrapeptides Using Cbz-Nprotected Dipeptidoyl Benzotriazolides Cyclo-tetrapeptides are useful intermediates in synthesis of drugs and drug-like molecules. This could be attributed to some of the characteristics of cyclotetrapeptides such as their low molecular weight, and favorable pharmacokinetic properties, as well as their ability to support a wide range of substituents and functional groups. Although cyclo-tetrapeptides could potentially be used for various pharmaceutical and industrial applications, their applications are currently limited because of the problems in their synthesis. The main problem for their synthesis is the difficulty in bringing the two termini in a linear tetrapeptide sufficiently close for the cyclization to occur. Such steric and conformational hindrance issues are due to peptide bonds in trans conformation, and the tendency of linear peptides to exist in more extended. We have used a Pd-catalyzed tandem-deprotection-cyclization reaction, to develop a novel methodology to synthetize symmetrical and unsymmetrical cyclic tetrapeptides, from open-chain N-cbz-dipeptidobenzotriazolides. The cyclo-dimerization reactions were successfully carried out with dipeptidobenzotriazoles as the starting materials, yielding cyclo-tetrapeptides. The cyclo-tetrapeptides cannot be prepared efficiently by previously reported synthesis methods. This novel methodology would provide a convenient tool for synthesis of a wide variety of cyclo-tetrapeptides that could potentially have applications in the pharmaceutical industry, catalysis, and material sciences. 7 Ryan Johnson Faculty Mentor: Peggy Borum Home Institution: University of Florida Research Field: Health-related (Pharmacy, Dentistry, Medicine, Nursing, Physical Therapy, etc.) InvestiGators Gator Team The Gator Team of the Investigators Research Honors Society focuses on research regarding HIV positive pediatric patients and infants exposed to HIV in utero. Both HIV infection and anti-retroviral medications can have a negative impact on growth, body composition, and overall metabolism. Our team utilizes nutrition and lifestyle modification education to combat the comorbidities such as insulin resistance, dyslipidemia, hypertension, and lipodystrophy. Our patient care program focuses on supplementing traditional clinical care through the collection of 24-hour diet recalls, anthropometric measurements, and 7-day activity recalls at UF Health’s weekly Infectious Disease Clinic. Additionally, personalized education packets are created for each patient outlining concerning trends within their diet and/or body composition. These packets are designed to give the patient an active role in improving health through lifestyle. The Gator Team has created unique tools, including the Gator Circle, which measures visceral adiposity, and the Cumulative Indices Assessments, which indicates risk for developing insulin resistance. The evaluation of the collected data is presented to our clinic colleagues in the form of a Metabolic Assessment document that becomes a part of the patient’s electronic medical record. Matias Kaplan Faculty Mentor: Jennifer Doudna Home Institution: University of California, Berkeley Research Field: Biological Sciences Structural Insights into Cas9, a Programmable DNA Targeting Enzyme In order to defend against phage infection, bacteria and archaea have evolved adaptive immune systems that rely on specialized genomic loci called CRISPR (clustered regularly interspaced short palindromic repeats) and CRISPRassociated proteins (Cas) to degrade foreign DNAs. DNA targets are recognized and cleaved by a ribonucleoprotein complex comprising CRISPRderived RNAs (crRNAs), which provide specificity via RNA:DNA base-pairing, and Cas9, which harbors two nuclease domains that cleave the foreign DNA. Importantly, Cas9:RNA has recently been reengineered to serve as a powerful new genome editing platform. Despite this success, little is known about the structure of Cas9 and how its conformation is affected by nucleic acid binding. In order to gain structural insights, we are using negative-stain electron microscopy (EM) to monitor Cas9 conformational changes upon its interactions with crRNA and target DNA. Cysteine-free Cas9 mutants were engineered allowing for specific labeling by introducing cysteine point mutants. Through a thiol targeting maleimide reaction, we were able to crosslink a biotin complex for use in EM. The static data obtained from EM will allow us to build a high resolution model of conformational changes induced upon DNA binding. This new information opens the possibility to engineer a second generation of Cas9s for improved efficiency and currently unexplored applications. 8 Rachel Newsome Faculty Mentor: Steven Bruner Home Institution: University of Florida Research Field: Biological Sciences Investigating Human Olfactory Receptor Function Using Structural Biology Human olfactory receptors (HORs) belong to the G-protein coupled receptor (GPCR) class of proteins, which are topologically defined as seven transmembrane helices, connected by three intracellular loops and three extracellular loops. The signaling pathway of HORs is characterized by the activation of the receptor via direct binding of a ligand to the binding pocket of the HOR, resulting in the activation of adenylyl cyclase, and the generation of an action potential that is then relayed to the brain. Our research seeks to determine the crystal structure of the first human olfactory receptor in order to understand the mechanism of ligand binding, and receptor activation. The gene sequence coding for three HORs were modified to allow the insertion of bacteriophage T4 lysozyme between the third and fourth intracellular loops, which has been shown to stabilize GPCRs and allowing for crystal formation. The recombinant gene sequence was expressed using the commercially available baculovirus expression system. Current research is focused on the purification of these receptors for crystallization trials. Muna Oli Faculty Mentor: Brent Reynolds Home Institution: University of Florida Research Field: Health-related (Pharmacy, Dentistry, Medicine, Nursing, Physical Therapy, etc.) The University of Calgary Complex adaptive systems (CAS) are changing collections of interacting components that react to their environments and to one another, an example being an ant colony in which each ant has a task, and acts on a few basic principles, yet the entire colony acts as one single organism. If the colony is threatened by a predator, the CAS is disrupted, and chaos ensues. Cancer cell biologists are now applying this ecological concept and thinking of a tumor as a collection of cells and considering how communication disruption may have implications on tumor progression. It is first important to determine if and how tumor cells communicate. It is suggested that tumor cell communication occurs through gap junctions (GJs). GJs are specialized channels that couple adjacent cells and permit the bidirectional passage of small molecules, allowing cells to communicate with each other and respond collectively. GJs have been shown to play a role in the regulation of processes involving cell growth. The role of GJ coupling in Glioblastoma (GB), and cancer in general is not well characterized. This research aimed to identify the presence of GJs in GB cells and determine the ability to down regulate GJ using drugs. GJ were identified through various techniques. Results indicated that GJ were present between GB cells and could down regulated by 50%. Tumor heterogeneity is a leading concern within cancer, and the evaluation of the role of GJs in tumor progression and treatment resistance could be harnessed as avenues for therapy, and for furthering our understanding of tumor biology. 9 Giselle Pacheco Faculty Mentor: Peggy Borum Home Institution: University of Florida Research Field: Health-related (Pharmacy, Dentistry, Medicine, Nursing, Physical Therapy, etc.) InvestiGators KetoGator Team The KetoGator Team, a part of the InvestiGators Research Honor Society, is focused on relieving seizures and comorbidities that result from anti-epileptic medications by providing Ketogenic Therapy to pediatric patients diagnosed with intractable epilepsy. Ketogenic Therapy is a high fat, low carbohydrate, adequate protein diet that has been proven successful in treating various neurological disorders. Because the mechanism of this therapy is still unknown, the KetoGator Team is focused on researching the Ketogenic Diet while monitoring each patient’s progress over time. To ensure that patients are receiving optimal treatment, the KetoGator Team creates and sends meal recipes to caregivers. Within the recipe, the caregiver has a list of brandspecific ingredients with gram amounts as well as serving and preparation suggestions. In order to improve individualized patient care, each patient is required to attend a clinic visit every three to four months where the KetoGator Team interviews caregivers and collects anthropometric measurements, diet records detailing which meals were consumed by the patient, and daily seizure records. Following the visit, the KetoGator Team enters the collected diet records into the Nutrition Data System for Research – a comprehensive database - that allows the KetoGator Team to view the nutritional composition of each meal the patient received. Ryan Quiñones Faculty Mentor: Alan Katritzky Home Institution: University of Florida Research Field: Physical Sciences Benzotriazole-Mediated Synthesis of Small and Medium Ring-Sized Cyclic Peptides A powerful synthetic method, cyclo-oligomerization allows efficient formation of various macrocyclic peptides, with the potential to create a plethora of dimer, trimer, and tetramer macrocycles for applications in medicine, drug design, and catalysis. Formation of diketopiperazines from intramolecular cyclization of dipeptide segments of natural amino acids occurs under N-deprotection and carboxyl group activation. Peptide segments containing β-turn inducing constraint element increases the difficulty of intra-molecular cyclizations; such segments include: oxazolines, oxazoles, thiazolines, thiazoles and imidazoles. Their rigid trans conformations and five-membered ring structures therefore make them ideal to serve as building blocks for the proposed synthetic strategies. In our previous investigations, we showed that the synthesis of cyclo-tetrapeptides can be achieved utilizing a palladium catalyzed tandem deprotection/macrocyclization strategy with readily available cbz-dipeptidoyl benzotriazolides. We now report that cbz-dipeptidoyl benzotriazolides can be cyclized in an intra-molecular or cyclo-oligomerization fashion to access different peptide macrocycles. 10 Timothy Scott Faculty Mentor: Connie Mulligan Home Institution: University of Florida Research Field: Humanities Y-genotyping of haplogroups E and J in the Yemeni population In the context of understanding human migration, Yemen represents an essential location along a southern migration route for the colonization of nonAfrican regions. The predominance of J haplogroups in the Arabian Peninsula and notable frequency in European populations, combined with a prevalence of the African E haplogroup across multiple continents, suggests these two haplogroups are ideal for understanding the diffusion of humans between Europe and Africa. Y-genotyping of 50 randomly sampled Yemeni male individuals revealed low genetic diversity in the region, while featuring a strong prevalence of M-267-defined J1 subhaplogroup, comprising 82% of the sample population. Analysis of these results in conjunction with frequency data representing regions across Europe and Asia suggests multiple conclusions: (1) The majority of Yemeni Y chromosome diversity is described by only haplogroups E and J, suggesting a long-term population history characterized by small size and geographic isolation, (2) southern Arabia is a good candidate for the origin of subhaplogroup J1, (3) J1 spread northward throughout the northern Arabian Peninsula as well as southern Europe. Furthermore, while there exists a significant frequency of subhaplogroup E1b1 in the southern Arabian Peninsula as well as throughout southern Europe, the subhaplogroup is virtually nonexistent in northern Arabia; (4) this result supports two separate migrations of E1b1 from Africa and restricted gene flow between southern Arabia and Europe. Yemen provides insight into the peopling of regions as humans dispersed from Africa Olga Sinyavskaya Faculty Mentor: Yona Levites Home Institution: University of Florida Research Field: Health-related (Pharmacy, Dentistry, Medicine, Nursing, Physical Therapy, etc.) Effects of anti-Tau Immunotherapy of rTg4510 in Tau Transgenic mice In order to rapidly and cost-effectively evaluate potential modifiers of Alzheimer’s disease (AD) pathology in mouse models, we have developed a “somatic brain transgenics” paradigm, established by delivery of gene constructs packaged into adenoassociated viral vectors and injected into the cerebral ventricles of P0 mice. The mechanisms underlying the abnormal phosphorylation and accumulation of Tau in AD remain unclear. Tau is a microtubule-associated protein, and in the diseased state conformational changes occurs that cause it to dissociate from microtubules leading to neurofibrillary tangles. These intracellular aggregates are considered toxic to some cell functions since typical AD pathology is characterized by plaques of aβ and the intracellular accumulation of tau. Anti-tau immunotherapy has recently emerged as a promising approach to target tau, but many mechanistic questions regarding the optimal form of anti-tau immunotherapy remain. We have recently observed that targeting phosphorylated tau in rTg4510 transgenic mice by single chain variable fragments (scFv) and intracellularly expressed intrabodies prevents its pathological accumulation. 11 Appreciation to Faculty Mentors Department Faculty Mentor Student Anthropology Connie Mulligan Timothy Scott Chemistry Alan Katritzky Justin Arami Evan Broggi Sadra Hamedzadeh Ryan Quiñones Chemistry Leslie Murray Jesse Gordon Chemistry Steven Bruner Rachel Newsome Entomology and Nematology Emma Weeks Julie Baniszewski Food Science and Human Nutrition Peggy Borum Scott Cohen Ryan Johnson Giselle Pacheco Mechanical and Aerospace Engineering Prabir Barooah George Armanious Medicine Roland Staud Halie Guelfi Molecular and Cell Biology Jennifer Doudna Matias Kaplan Neuroscience Yona Levites Olga Sinyavskaya Neurosurgery Brent Reynolds Muna Oli Physical Therapy David Fuller Parisa Amirzadehasl Surgery Scott Berceli Leanne Dumeny 12 Support Faculty Support Dr. Anne Donnelly Program Director Donna Jackson Program Assistant 2013-2014 CURBS Executive Board Muna Oli President Frances Ooi Co-Vice President Timothy Scott Co-Vice President Mindy Wang Secretary Joshua Williams Treasurer Bryce Bergeron Peer Mentoring Lindsay Orr Director of Public Relations Aishwarya Vijayan Director of Workshops and Seminars Alexandra Sabin Co-Director for K-12 Outreach (Elementary) Carolina Sarmento Co-Director for K-12 Outreach (Middle School) Bryce Edwards Co-Director for K-12 Outreach (Middle School) 13