Chemistry is an experimental science. As in all experimental sciences, we ask questions and devise experiments to help us answer those questions. The research process involves identifying an interesting question or problem to investigate, devising experiments to help find a solution to the question or problem, revising our approach or even revising the question based on experimental results, and repeating the process. Experimental work can involve mixing chemicals in a hood, programming a computer, working with instrumentation, or a variety of other activities.
Infection with ebolavirus causes a hemorrhagic fever (EHF) with case fatality ratios among the highest of any known communicable disease . With no available antiviral therapies for EHF, patient isolation, which provides no hope to the afflicted individual, remains the only effective means of dealing with an epidemic of ebolavirus . While natural outbreaks of the manifestation of this virus in humans appears to be localized to sub-Saharan Africa, the potential for the use of ebolavirus as a weapon of biological terrorism has resulted in the classification of the virus both as a Select Agent and as a Category A Biological Terrorism Agent. As such, research with the virus is highly regulated (and therefore relatively scarce). Viruses are infectious agents with either RNA or DNA as their genetic material. The nucleic acid used by ebolavirus is RNA , and this RNA is a single, long piece. Viral genetic material is always housed in a protein coating. The number of proteins encoded by different viruses and the ways in which these proteins are associated with the genetic material is diverse. It is known that the genomic RNA of ebolavirus must always be tightly associated with some subset of viral proteins. The proteins that the RNA keeps around itself throughout its lifecycle are called the nucleocapsid proteins and this RNA -protein complex is called the nucleocapsid. In ebolavirus, the nucleoprotein (NP) is the major protein component of these RNA -protein complexes. The mechanism by which NP specifically coats ebolavirus RNA is unknown. We are working towards the delineation of the RNA -protein interactions that govern this essential step in the viral lifecycle.
Hilary J. Eppley does research into the effect of solvent environment on reactions to form inorganic coordination polymers and multinuclear aggregates of metal ions. In particular she is interested in the use of ionic liquids (like table salt, only liquids at room temperature) for these reactions.
In addition to her chemistry research with undergraduates, she is working with nine other inorganic chemists from across the country to run a network for faculty who teach inorganic chemistry. She has been doing development work on the group's teaching website, VIPEr: http://www.ionicviper.org and is planning a faculty development workshop to develop new materials for it. The work of IONiC has been supported by 3 National Science Foundation Grants, the latest which is a 5 year grant worth over $1 million.
Work in my research group currently has three major foci with particular areas getting more or less emphasis depending on student interest. I have on-going projects synthesizing and characterizing gold nanoparticles with a variety of capping agents for use developing optical biosensors, using reverse micelles as way to look at the behavior of water in confined environments and transport across lipid boundaries, modeling laser-molecule interactions theoretically. All of these projects contribute to our fundamental understanding of various molecular properties. With the gold nanoparticle project, we are currently working to control the size growth of the gold nanoparticles under various green chemistry syntheses and to attach a library of biomolecules to the capping agents. We use steady state and time resolved spectroscopies of various probe molecules to elucidate the structure and dynamics of our reverse micelle systems. In our laser-molecule interaction studies we are specifically looking at IR energy transfer and redistribution in small molecules such as HF or OCS.
Next generation DNA sequencing is an enormously powerful tool in the discovery and diagnosis of rare genetic disorders. In collaboration with the Rare Genomics Institute, we analyze the genetic sequences of patients with undiagnosed genetic disorders in search of causative variants, and we connect families with researchers who may be able to help move their case forward.
Other projects involve the development of new ways to envision and share ideas about the molecular world. They draw on connections between biochemistry, computer science and art. For example, a collaboration with artist Julian Voss-Andreae, DePauw art professor Jacob Stanley, and Klaus Schulten's lab at the Beckman Institute, resulted in a large-scale steel protein sculpture now permanently installed in the Julian Science Building. An article about this project was published in PLOS Biology in 2013.
Another recently completed project involved creating an iOS app to help students practice 3-dimensional thinking in organic chemistry. The app is called “Molecule Match”, and you can download it free from the iTunes store.
We’re also interested in molecular animation. We make animations; for example, this stop-motion animation of cyclohexane conformations, and this visualization of the HIV virus which won second place in the CGSociety autoPack challenge. We also develop tools to help others create molecular animations, such as proteinRig, a script that simulates the random motions of protein side chains inside professional animation software.
If you are a DePauw student and want to talk (about these projects, or even better, your own ideas), feel free to email me or stop by my office.
My research group works primarily in the area of organic synthesis. Specifically, we are investigating a tandem aldol/epoxidation reaction using sulfur ylides and related compounds. This reaction is highly stereoselective. This means that it constructs an organic molecule in a way that very specifically controls the three-dimensional arrangement of the atoms in the molecule. This kind of control is very important in the preparation of pharmaceutically active compounds. Currently our research is focused on testing the biological activity of the products from this reaction using a Brine Shrimp Lethality Assay. Additionally, we are developing the ability to use our aldol/epoxidation product to make a variety of interesting structures. These compounds can then also be tested for biological activity. This research involves typical organic synthesis techniques and usually anaerobic and anhydrous reaction conditions. We also hatch brine shrimp and expose them to various concentrations of our compounds to see how the shrimp respond. We have identified that our compounds have a significant level of toxicity to the brine shrimp. Other compounds with comparable activity have been shown to have therapeutic value.
My research interests fall into two broad areas: the analysis of trace metals in sediments and the development of curricular materials.
Past projects in the analysis of sediments include a study examining the effect of tubificid oligochaetes—a small fresh-water annelid worm—on the movement of zinc ions across the sediment-solution interface; a study examining the pollutional history of Indiana lakes by measuring the concentrations of trace metals at depth in sediment columns, and a study characterizing limitations to the BCE sequential extraction scheme when applied to carbonate-rich sediments. Future work in this area will focus on exploring the possibilities and limitations of sequential extractions.
Past projects in the area of curriculum development include the design of new laboratory experiments that illustrate important concepts in analytical chemistry, the preparation of an electronic textbook for courses in analytical chemistry, and the development of materials to promote active-learning in analytical chemistry. Future work in this area will focus on developing new experiments for use in Chem 260 and Chem 450, exploring the possibilities and limitations of electronic textbooks, and using the statistical software program R to develop active-learning materials for analytical chemistry.
During the summer of 2014, students in my laboratory will be working on a variety of projects. The first of these focuses on synthesizing nanoparticles that will be used in a low-cost detection scheme for neglected tropical diseases. We will investigate various ways of chemically modifying these nanoparticles so that they will interact with the DNA of the disease and then be captured in a paper substrate. A second project will examine the use of small gold substrates for use in surface-enhanced Raman spectroscopy. This material may make it easier to perform rapid analysis of aqueous samples which might harbor chemicals of interest, such as an environmental pollutant. In the third summer project we will use electrochemical methods to examine the properties of a unique class of materials called ionogels. Students in Prof. Eppley's lab have synthesized these ionogels, which may potentially have several chemical applications. Examining the electrochemical properties of these materials is important with regards to gaining a more complete understanding of their chemical behavior.
Our current interest focuses on understanding transcriptional regulation in Archaea utilizing structural, bioinformatic, and biochemical analyses. Towards this, we are using molecular and biochemical techniques to generate clones and express and purify transcriptional factors. We have generated diffraction quality crystals of one transcription factor in the presence and absence of metals. Crystallographic data has been collected at the Argonne National Labs in Chicago. Many of the students who have worked on this project are now in various graduate and medical schools across the county. In the past five years three students have completed senior thesis projects.