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2013

LU-PRISM Projects

Immunology – Dr. Amorette Barber

The creation and characterization of chimeric antigen receptors targeting the PD-1 receptor

Despite advances in treatment options, cancer remains the second leading cause of death in the United States. One alternative is to use cells of the immune system, specifically T cells, as a therapy for cancer. In order to enhance recognition of tumors by T cells, chimeric antigen receptors, which consist of intracellular signaling domains fused to receptors that recognize tumor antigens, can be created and expressed in T cells. Previously, we engineered a chimeric NKG2D receptor that allows T cells to recognize and kill many types of cancers, including lymphoma, myeloma, and ovarian cancer. However, novel chimeric antigen receptors need to be designed in order to target other types of tumors. One receptor that is a prospective target for a new chimeric antigen receptor is PD-1. The ligands for the PD-1 receptor are overexpressed on many types of tumors and thus are potential tumor-specific targets. This project will focus on the creation of chimeric antigen receptors targeting the PD-1 receptor and will employ methods similar to those used to create the chimeric NKG2D receptor. Through genetic engineering, the extracellular domain of the PD-1 receptor will be fused to different intracellular signaling domains in order to study which combination of downstream pathways activate the strongest anti-tumor immunity. These receptors will be expressed in T cells and tested for anti-tumor functions, including tumor cell lysis and cytokine secretion, against PD-1 ligand positive and negative cell lines. Through participating in this project, students will learn multiple techniques including cell culture, genetic engineering, PCR, flow cytometry, ELISAs, and statistics.

Molecular Biology/Genetics – Dr. Dale Beach

Development of a modular expression vector system that can shuttle between budding yeast species

In the budding yeast Saccharomyces cerevisiae, cellular growth during the normal, vegetative cell cycle occurs almost completely within the daughter cell. The asymmetric growth of the daughter cell creates a polarized model system to study directed, intracellular transport.  As in other eukaryotic organisms, mRNA can be localized to specific region resulting in a pre-localization for the resulting protein.  The RNA-binding protein, SHE2p is responsible for packaging the mRNAs into a transport particle and facilitating the transport of bound messages. While well described for S. cerevisiae, there is little information regarding the role of SHE2p in other species of budding yeast. Using published genomic sequences, we have identified genes similar to SHE2 in other yeast species and are working to determine if these homologous proteins have a similar localization pattern.  Molecular studies in yeast species other than S. cerevisiae are hampered by a lack of appropriate reagents to create recombinant gene expression systems. Using the BioBrick modular design system popularized through Synthetic Biology applications, we are developing a gene expression vector system that can be readily modified to allow expression of recombinant gene constructs is different yeast species by swapping genetic elements such as centromere and autonomous replication sequences (ARS).  To address the primary aim of determining the changing evolutionary role of She2p, the undergraduate summer research program will support the design and construction of one or more integrated vector systems, as well as in-vitro testing of the new plasmids.

Astrophysics - Dr. Rodney Dunning

The effect of a Jupiter-like planet on small Earth-like planets

My research involves creating computer of models of extra-solar planetary systems. Specifically, the project focuses on calculating the habitable zone (the range of distances at which a planet could support a liquid-water environment on its surface) for a parent star, and then examining the long-term orbital behavior of an Earth-like planet placed in that zone. Most of the systems astronomers have discovered contain large, Jupiter-like planets with orbits much more non-circular than the orbits in our solar system. My student and I will investigate the effect of a Jupiter-like planet on small Earth-like planets to determine the likelihood of the Earth-like planet being ejected from the habitable zone. The ultimate goal is to develop a set of parameters that will help astronomers identify the most likely stellar systems where potentially life-supporting planets might be found. If time allows, we will conduct a similar study the orbital behavior of Earth-like planets in double-star systems, since the majority of stars exist as members of double-star systems.

Environmental Science – Dr. Kenneth Fortino

An investigation of the effect of biodiversity on the storage of organic carbon in the sediments of small ponds

Understanding the factors that control carbon cycling is critical to understanding how ecosystems will respond to climate change.  One gap in our knowledge of carbon cycling is the role of small ponds in carbon dioxide production and organic carbon storage.  Small ponds can store large amounts of organic carbon in their sediments because they capture organic material from their watersheds.  If this carbon remains in the lake sediments, it can be subtracted from atmospheric carbon and may mitigate some of the effects of climate change.  However, if the organic carbon that gets washed into the lake is consumed by sediment microorganisms, the carbon will be returned to the atmosphere as carbon dioxide, potentially exacerbating climate change.  I am proposing a project to investigate the effect of biodiversity on the storage of organic carbon in the sediments of small ponds.  Preliminary data suggest that the functional diversity of sediment insect communities alter the rate at which the sediment microorganisms breakdown organic carbon.  The objective of the proposed project is to expand upon these preliminary findings and measure the effect of sediment-dwelling insect function diversity on the rate of sediment organic matter breakdown in the field.  We will manipulate the functional diversity of sediment insect communities in small chambers in the lake and quantify changes in sediment organic matter breakdown by calculating sediment oxygen demand. These findings will expand our knowledge of how potentially climate sensitive factors insect community composition) control the storage of organic carbon in lake sediments.

Behavioral Neuroscience – Dr. Adam Franssen

Pup recognition in the rat (Rattus norvegicus)

It is often said that there is no greater bond than that between a mother and her child.  While touching, the sentiment begs two questions: "Why?"  and, "what does that mean for adoptive parents?"  The answers may come from an unlikely quarter: by research on mother rats.  Studies indicate that mother rats preferentially care for their own pups (OWN) over pups from another mother (ALIEN).  Mother rats would still eventually care for alien pups, but the indication is that a close bond exists beyond the desire to care for young in general (Beach and Jaynes, 1956).  However, the underlying neural basis for the responses of mothers to pups is unclear.  One indication of how the mother-pup bond forms may come from investigations of the mother brain.  Previous research has shown that mothers experience differences in their brain chemistry and structure due to the hormones of pregnancy, parturition, and motherhood in animal models (e.g., Kinsley and Lambert 2008; Lambert and Kinsley 2008).  Other studies indicate that maternal experience alters neural plasticity, which may contribute to brain regions and behaviors that support care of young.  For example, compared to virgins, mothers have denser populations of hippocampal dendritic spines, indicating that more neural connections have been made (Kinsley and Lambert 2006).  Here, we attempt to replicate the pup-recognition study conducted by Beach and Jaynes and expand upon their findings by examining the brains of studied mothers.  We hypothesize that the difference in response to OWN versus ALIEN pups will be reflected in the hippocampi of mother rats.

Synthetic Chemistry – Dr. Christopher Gulgas

Designing luminescent lanthanide sensors for capsaicinoids

Everyone knows when they have bitten into a hot pepper, whether by accident or not.  The bite releases a flood of molecules that interact with sensory nerves in the mouth.  Capsaicin is the primary molecule responsible for the sensation of heat and pain that arises when eating spicy foods.  The capsaicinoid family is a subset of the more general class of molecules known as vanilloids.  These antioxidant molecules have antitumor and antimicrobial properties and are utilized as topical analgesics for treating pain.  The primary efforts of my current research group are in designing luminescent molecular sensors for capsaicinoids and characterizing the nature of the binding interactions.  The sensor molecules are lanthanide complexes of europium or terbium, both luminescent in the visible range of the spectrum.  The binding of capsaicinoids to the lanthanide complexes has been shown in our lab to induce a drastic luminescence augmentation that serves as a signal.  Applications from this basic research range from inexpensive determinations of capsaicinoid concentrations in hot sauces to the development of lanthanide molecular probes for capsaicinoid-based drugs in cell studies.  In the summer of 2013, an undergraduate student working in my lab can expect to design a 2nd generation EDTA-based lanthanide chelate and study its ability to detect a range of capsaicinoid molecules in aqueous solution.  This project will require organic synthetic methods and characterization including NMR, IR, UV-VIS and fluorescence spectroscopies.  The proposed molecules to be synthesized are novel structures and suitable for student presentations and publication in peer-reviewed journals.

Astrophysics – Dr. Gary Page

Distribution of galactic dark matter temporarily captured into solar orbit

The purpose of this research is to investigate the distribution of Galactic dark matter that is temporarily captured into orbit about the Sun. This capture is affected by the three body interaction between the Galactic barycenter, the Sun, and the dark matter particle. As such, the exact nature of dark matter is not important. As is well known, the general three body problem is not soluble in closed form. Since Newton's time, many very capable people have attempted to make headway against this problem's complexities. In attempting to model the temporary capture of Galactic dark matter into orbits about the Sun, the circular restricted three body problem, and its special case the Hill Problem, provide an excellent approach. Using this approach, we will numerically integrate the equations of motion to determine the time-averaged distribution of position and velocity associated with a set of initial conditions describing the three body interaction. Because of the multiplicity of interaction geometries, we will Monte Carlo the interactions to be consistent with the assumed Galactic dark matter distribution and the known parameters of the Sun’s rotation about the Galaxy. The results of this research will inform the ongoing searches for dark matter particles by defining any local enhancements to the density of Galactic dark matter in the vicinity of the Sun.

Forensic Chemistry – Dr. Sarah Porter

The development of chromatographic methods for the identification of smokeless gun powders and gunshot residues

There is an interest in the forensic science community in the identification of gunshot residue (GSR) on the hands and clothing of a person who is suspected of having fired a weapon.  Typically, gunshot residue is conclusively identified by the presence of the inorganic components barium, lead, and antimony.  The presence of these metals is usually confirmed by scanning electron microscopy or quantitatively by atomic absorption or inductively coupled plasma atomic emission spectroscopy.  In recent years, however, organic compounds have been used in gun powders as primers and propellants, most notably in modern "smokeless" gun powders.  These compounds include nitrocellulose and a host of other nitrogen containing aromatic compounds.  This project will focus on the development of chromatographic methods for the identification of GSR.  Specifically, high performance liquid chromatography (HPLC) with fluorescence and UV detection will be applied to analyze the compounds commonly encountered in smokeless powders and GSR.

Climatology – Dr. Kelsey Scheitlin

Investigations in tornado alley: How humans interact with severe storms and an analysis in severe weather climatology

This research experience will focus on tornado occurrences in the Great Plains of the United States, i.e. tornado alley.  The student will develop two research questions, collect data in the Great Plains for two weeks, and return to analyze their data and draw conclusions. There will be two distinct investigations, the first being a study involving human-environment interaction, specifically how people interact with severe weather.  My current research suggests that storm chasers have increased the number of tornado reports in rural areas. One could argue this increases the safety of residents because when a chaser reports a tornado, the storm that produced it becomes "tornado warned" and residents can prepare appropriately. Others argue storm chasers cause dangerous traffic situations during extreme weather events. The student may choose to study this topic in depth to determine the impact of storm chasers on severe weather safety. Other possible topics are local perceptions of tornado watches and warnings, or regional variations in severe weather perceptions.  The second investigation will be an analysis of tornado occurrences. There are many possibilities for research in this area, including the relationship between tornado occurrences and various climate indices, temperature changes produced by a severe storm, and the validation of severe weather forecasts.  Upon the completion of their investigations the student will develop qualitative and quantitative research skills, gain understanding of severe weather phenomena, increase their awareness of the physical and human geography of the central United States, and appreciate the complex relationship between humans and their environment.

Mathematics Education - Dr. Leah Shilling-Traina

Engaging in action research to inform mathematics instruction in a university precalculus course

This research experience will introduce an undergraduate mathematics major seeking secondary education licensure to the theory and practice of teacher-led inquiry within mathematics education, and will engage them in a school-based action research project. Broadly speaking, action research provides teachers (and in this case, pre-service teachers) with the opportunity to professionalize themselves as teacher-as-researchers by making use of social scientific research approaches. The undergraduate chosen to participate will design and conduct an action research project that: involves an exploration of the existing data in the research; focuses on problems from their direct environment (primarily within the context of the university's precalculus course); links the research to evaluations; analyzes the existing practical situation; and integrates theory from the research literature. One major goal of this kind of research is to help narrow the gap between theory and practice in mathematics education.

Mathematics – Dr. Thomas Wears

Studying the geometry of the Heisenberg space Nil3 using the Fels-Olver approach to moving frames

In the traditional introduction to the study of differential geometry, an undergraduate student begins by studying curves and surfaces that are immersed in Euclidean 3-space (E3) and they typically depart when one arrives at the idea of an abstract surface. This project aims to bridge this gap by studying curves and surfaces that are immersed in topological R3 equipped with a Non-Euclidean geometry. Specifically, the student will be studying the geometry of the Heisenberg space Nil3. While Nil3 is topologically equivalent to R3, the geometry of Nil3 is both rich enough (i.e. the dimension of the isometry group is 4) and sufficiently different from E3 that many classical geometric problems can still be addressed using advanced and modern mathematical techniques.  We will study the geometry of curves and surfaces in Nil3 through the lens of the Fels and Olver equivariant approach to moving frames. In particular, we will address the problem of determining when two surfaces (or curves) in Nil3 are equivalent under the action of the isometry group of the space. The goals will be: i.) Find a sufficient number of differential invariants that will allow us to completely solve this problem under a suitable non-degeneracy hypothesis; and ii.) find a minimal generating set for the algebra of differential invariants of a surface in Nil3. We will compare and contrast our results with the results available through the traditional approach to moving frames. Additional topics of study to be addressed, depending on interest of the student, include invariant submanifold flows (e.g., curve shortening flows), invariant variational problems, or other classical geometric problems in Nil3 (constant mean curvature surfaces, minimal surfaces, etc.). All topics will be addressed using the Fels-Olver approach to moving frames.

Developmental Biology – Dr. Wade Znosko

A determination of the short-term and long-term effects that specific agricultural contaminants have on aquatic life

Zebrafish have been used as a model to study many different biological areas, including neurobiology, development, and behavior. Zebrafish form a functional, beating heart just two days after inception.  During this time, in addition to a heart, a brain, eyes, kidneys, and most other organs are also formed.  This rapid organ formation allows zebrafish to be examined to determine the critical events that take place early during development.  I previously identified a specific family of proteins that are responsible for proper heart formation.  Normally, all zebrafish hearts loop in a certain direction.  Without these proteins present, the heart is looped in completely the opposite direction, or is not looped at all.  Interestingly, these proteins do not function directly upon heart cells during development, but rather alter cilia movement in a completely different region of the developing embryo.  My future work involves looking at other novel, uncharacterized proteins within zebrafish to analyze a possible role in heart development.  A second, more immediate project I would undertake this summer with an undergraduate is to examine specific agricultural contaminants found within local Virginia waterways and determine what types of developmental effects these contaminants are having on aquatic animals.  In addition, this study would fill a void currently noticed within water quality programs.  A main goal of this study is to determine the short-term and long-term effects that specific agricultural contaminants found in our waterways have on aquatic life, specifically focused on heart, gut, and brain development.