Faculty Research Interests
Research in the sciences at Gonzaga University covers a broad range of topics. In addition to the traditional definitions of the disciplines, we offer cutting-edge research at the interface of biology, chemistry, mathematics and physics. Below you will find short descriptions of the individual research interests and/or projects in faculty labs.
Not all faculty have open research positions! Students interested in applying for a research position must check with the research mentors below to make sure there is an open position before beginning the application process. To apply, fill out the Application for Independent Study and submit to Angie Hinz.
For more independent research opportunities, check out our neighbors across the river at WSU-Spokane, particularly in the College of Medical Sciences and the College of Pharmacy. Not all WSU faculty can take a research student but all welcome the chance to talk about their research so feel free to contact them regarding possible opportunities.
If your research will make use of the Gonzaga Greenhouse, you will find more information here.
Faculty Research Interests
Scroll down to view more detailed information for all faculty members, or click on a faculty member’s name to go to that specific laboratory.
Elizabeth Addis: Mechanisms of Life History Control
Kirk Anders: Eukaryotic Genetics Using Yeast as a Model Organism
Julie Beckstead: Interactions Between Invasive Plant Species and Seed Pathogens
Mia Bertagnolli: Signaling Molecules Involved in Cell Adhesion, Migration and Disease
Carla Bonilla: Molecular Mechanisms of Bacterial Stress Response
Gary Chang: Ecology of Predatory and Herbivorous Insects
Bill Ettinger: Research Areas: Disinfection of Catheter Ports and Characterization of Viral Proteins
Joey Haydock: Reproductive Partitioning in the Cooperatively Breeding Acorn Woodpecker
Hugh Lefcort: Predator/Prey Relations in Aquatic Snails
Marianne Poxleitner: Evolution of Cocaine biosynthesis and Genetic Enhancement of Crops
Helen Smith: Cicadian Rhythms and Neurodegenerative Diseases in Drosophila melanogaster
Nancy Staub: Salamander Evolutionary Biology
Brook Swanson: Evolution of Complex Mechanical Systems in Animals
Kylie Allen: Methane production and consumption in anaerobic envoronments
David Cleary: Synthesis and Characterization of Extended Inorganic Compounds with Applications to Chemical Sensors, Batteries, and Catalysis
Matt Cremeens: Neuropeptides: Neuroscience for the Organic Chemist
Jeff Cronk: Enzymatic and Structural Studies of β-Carbonic Anhydrase
Osasere Evbuomwan: Design and synthesis of biomedical imaging agents for cancer and neuroimaging
Greg Gidofalvi: Computational Chemistry/Electronic Structure
Eric Ross: Stationary Phase Development for Chromatographic Analysis of Biomembrane Interactions
Jennifer Shepherd: Rhodoquinone Biosynthesis in Parasitic Helminths
Joanne Smieja: Household Water Treatments
Stephen Warren: Synthesis and Development of a Diagnostic Agent for Neurodegenerative Diseases and Type 2 Diabetes
Jeff Watson: Mechanism of Bacterial HMG-CoA Reductase, a Target for Novel Antibiotics
Shawn Bowers: Bioinformatics and Biodiversity Data Discovery
Nathanial Burch: Probability, Stochastic Processes, Nonlocal Evolution Equations, and Mathematical and Statistical Ecology
Bonnie Dichone: Mathematical Modeling, Interaction-diffusion Equations, Turning Patterns, Population Dynamics, Desertification
Erik Aver: Primordial Helium Abundance
Research in Biology
My research is broadly focused on physiological and evolutionary ecology, and specifically on the evolution of mechanisms that control life history strategies. I use vertebrates (currently yellow-bellied marmots and painted turtles) as my study systems because they exhibit a wide range of life strategies that frequently diverge from those of traditional model organisms. Taking a holistic approach, my work combines ecological and hormonal measurements in the field with genetic and hormonal analyses in the laboratory.
Urbanization of yellow-bellied marmots. Spokane is famous for its marmots. Marmots usually do not live in urban areas, although the prevalence of them is increasing. How can some marmots flourish in urban areas, such as Spokane, while others do not? Work this summer will focus on studies of marmot predator density and behavioral patterns as well as optimization of hormone assays.
I am interested in genes, chromosomes, and genomes: how they contribute to the traits of an organism, how they are transmitted during replication or cell division, and how they can change from generation to generation. My research makes use of two kinds of life forms: bacteriophages and brewer's yeast. Although my yeast lab is full, I am recruiting students for several different projects involving bacteriophages.
1. The first project is aimed at the question, “How do viruses control the expression of their genes?” To answer this question, we are cloning pieces of DNA from O cluster phages and testing them to see if they have properties that promote transcription of mRNA. Characterization of these promoters should give insights into their function, their properties, and their evolution. Students who are interested in participating should consider applying for BIOL 405L. (See http://goo.gl/rlcl9T for more information.)
2. The second project is in the structural and evolutionary analysis of phage genomes. A number of interested phages have been discovered at Gonzaga that need to be analyzed and published so that the scientific community can make use of them. I am recruiting students who are interested in computational research to annotate and analyze phage genomes using bioinformatics methods. This project has the potential to lead to molecular biology bench work for students particularly interested in pursuing their findings.
Note: Dr. Beckstead is not accepting new students for Fall of 2015.
Projects will focus on microbial ecology, plant-pathogen interactions, and invasion biology. I work on an invasive plant, cheatgrass (Bromus tectorum) that has devastated the Intermountain West. My long-term goal is to eliminate this invasive species and provide land managers with tools to restore cheatgrass-infested natural areas to native plant communities. I currently have two ongoing projects.
First, my lab works on a seed pathogen called Pyrenaphora semeniperda. The common name is black fingers of death because this fungus looks like little black fingers protruding from dead seeds. This is a naturally occurring pathogen in the western United States. We have a patent with the Forest Service to use this fungus to control cheatgrass. My past students have done a variety of interesting projects with this fungus, which include publications on the modeling of its growth, trade-offs between toxin production and growth, and the effects of plant litter on its pathogencity. Secondly, my lab works with die-off pathogens. In the past decade land managers have noticed areas of dead cheatgrass within a monoculture of living cheatgrass. Nobody knows who is causing these die-offs. We suspect that fungal pathogens are involved.
The research work will involve basic microbiology skills (aseptic techniques, making various types of agars, and culturing of fungi), seed germination experiments, seedling experiments, and collections of field samples for processing and/or experiments. Preference will be given to students who have completed Ecology (BIOL 206).
Note: Dr. Bertagnolli is not accepting new students for Fall of 2015.
As a cell biologist, I am interested in signaling pathways involved with cell adhesion and migration, and how alterations in these processes lead to disease. For example, many individuals with colon cancer have mutations in the Adenomatous Polyposis Coli (APC) gene, which affects cell adhesion and migration and ultimately results in tumor formation and metastasis. Patients with diabetes have altered signaling pathways that result in tissue injury. Using cells cultured in the lab, we can manipulate the genetic and/or physical environment of the cells to mimic the conditions they would experience in patients with these conditions and then study specific parts of signaling pathways that are altered by these conditions. Undergraduate students who participate in these projects become independent in the research laboratory and are exposed to basic laboratory skills as well as more advanced techniques such as cell culture and sterile technique, microscopy, gel electrophoresis and Western immunoblotting. Students typically take Cell Biology (BIOL 201) prior to working in my lab.
This project will focus on original experiments designed to study signaling molecules involved in pathways that lead to tissue injury in diabetes. Control epithelial cells grown in culture will be compared to those that are given high levels of glucose, similar to the conditions found in diabetic patients. Cell morphology, growth rate and adhesion will be analyzed under these conditions. In addition, the distribution of signaling molecules thought to be involved in diabetic pathways will be compared. Laboratory techniques used in these experiments include growing cells in culture, microscopy (both light microscopy and fluorescence microscopy), and image analysis. In addition, the student will gain significant experience in experimental design and data analysis, and the opportunity to interact with collaborators at the Providence Medical Research Center in Spokane.
I am fascinated by the ability of bacteria to survive in all kinds of environments. My research focuses on studying the response to environmental changes of the soil bacterium, Bacillus subtilis; that allow it to survive stressful conditions. B. subtilis is the model Gram positive organism because of its ease of genetic manipulation, sequenced genome and conservation with other pathogenic bacterial species. Bacteria, pathogenic and nonpathogenic, live in complex environments and must monitor their surroundings for nutrients, noxious chemicals, predators, etc. They accomplish this by using proteins that sense the environment (sensor proteins) and proteins that enact changes in gene expression (transcription factors) that alter the physiology of the cell to accommodate the changing conditions. I am interested in understanding the proteins involved in this bacterium’s stress responses at a molecular level.
Student projects will include testing the role of these sensor proteins and transcription factors using in vivo assays such as 1) bacterial survival after exposure to stress on solid and liquid media and 2) understanding the role of sensors proteins in biofilm formation, a form of stress response, by assaying mutants for their ability to form biofilms. Other projects are molecular in nature and include 3) measuring gene expression of stress responsive genes using RT-PCR of different mutant B. subtilis strains and 4) biochemical characterization of sensor proteins in the presence of stress signal molecules to identify activating and regulatory step
The landscape of Spokane County is a blend of urban and non-urban habitats. The species that live here can respond in different ways to urbanization. Our research team focuses on understanding the contrasting response of a weed, Dalmatian toadflax, and its biological control agent, an herbivorous weevil, to Spokane's landscape. In short, the weed is more abundant in urban areas while the weevil is more abundant in non-urban areas, and we are trying to explain why.
During summer 2015, we will continue working on the Dalmatian toadflax system by conducting small-scale field experiments to test hypotheses about weevil behavior. In addition, I am actively developing new research projects that will be rooted in the natural history of the Spokane region. Prospective students should reflect upon whether they would be interested in spending time performing basic observations of insect biology. If you are, then I would encourage you to contact me so we can further discuss potential projects.
Disinfection of catheter ports
Hospital acquired infections are a class of illness that are seemingly senseless; after all people go to hospitals to get well. Unfortunately, people in the hospital are also ill and quite susceptible to picking up infections. In hospitals there is a high concentration of other ill patients, and nurses, doctors, and other hospital staff can shuttle microbes amongst them. In the United States there are an estimated 1.7 million hospital acquired infections each year, leading to roughly 99,000 deaths. One class of hospital-acquired infection is central line-associated bloodstream infections (CLABSI). In this case microbes are introduced directly into the bloodstream through a catheter port. There are roughly 250,000 CLABSI infections each year, with mortality rates ranging from 12-25%. Catheter ports are common routes for microbes to enter the bloodstream. Our research involves a commercial product produced to disinfect and protect catheter ports. Shown below is a typical blue catheter port, and a green disinfecting cap. We are working with Hyprotek, a Spokane-based company that produces catheter-disinfecting caps. We contaminate catheter ports in the laboratory with different strains of bacteria, and then test to see how many bacteria remain after treatment. Individuals working on this project will learn basic microbiological skills, be involved in production of reports to Hyprotek, and be involved in regular lab meetings.
Characterization of Viral Proteins
Bacteriophages are viruses that specifically infect and often kill bacteria-they are harmless to humans. Bacteriophages are also probably the most abundant biological entity on earth, with an estimated 1031 phages worldwide. The SEA-PHAGES program (http://seaphages.org/) was established to give undergraduate students a chance to do real research on bacteriophages. Each team of students isolates a new unique bacteriophage and begins to characterize it. Students in the program have already found almost 6000 unique phages, of which 1000 have had their genomes sequenced. We know much less about the proteins that these viruses produce. Are the proteins part of the intact bacteriophage, or any produced early or late in the infection cycle? In order to characterize these proteins we need a way to find discover at what part of the phage life cycle each protein is produced. To discover answers to these questions, we will be growing bacteriophage on their bacterial host and capturing protein extracts at different times during the infection cycle. The protein extracts will be sent off for sequencing, we then will associate the protein sequences with different genes in the viral genome. Students working on this project will learn basic microbiological skills, be involved in the production of reports to our Gonzaga collaborator, Dr. Marianne Poxleitner (currently at the Howard Hughes medical Institute in Maryland) and be involved in regular lab meetings.
The general goal of the project has been to explicitly test hypothesis concerning reproductive partitioning in the cooperatively breeding acorn woodpecker, which have been under study at Hastings Natural History Reservation in central coastal California since 1971. What is cooperative breeding and what is reproductive partitioning? Cooperative breeding refers to social species in which the parents as well as other individuals in the social group provide care for offspring (termed alloparental care). Reproductive partitioning refers to distribution of parentage in social groups in which more then one breeder of each sex competes to breed. In most cooperatively breeding birds, social groups only contain a breeding pair and their offspring that do not breed, at least in part due to incest avoidance, so reproductive partitioning is not an issue. Acorn woodpeckers are unusual among cooperatively breeding birds in that social groups can consist of up to seven males that are unrelated to up to three females within a single social group, in addition to their offspring that are also group members. Thus, reproductive partitioning, which can range from egalitarian with each individual obtaining about equal reproductive success to high skew where a single individual of each sex monopolizes breeding, becomes an important component of each individual’s fitness. Several hypotheses have been proposed that make predictions for the amount of skew, based on factors including within sex relatedness, competitive ability and probability of successfully dispersing to another group. The goals off my students have involved collecting parentage information to test a specific one of these hypotheses.
A critical question to understanding the fitness costs and benefits of sociality in acorn woodpeckers is to obtain parentage information on reproductive partitioning within groups that contain at least two potential breeders within a sex. Because group structure varies considerably (number of potential breeders, age structure, genetic relatedness, and genealogical relationship), information on many groups is required to build a complete picture.
Previous work with students from Gonzaga University has produced the development and optimization of microsatellite primers to determine parentage as well as individual genotypes for 800 individuals (on up to 12 loci). My students have worked on relatively small sets of groups that are similar in structure (e.g. 2 potentially cobreeding males and a single female breeder) addressing specific hypotheses. Despite the wealth of data produced thus far, more data is needed, especially in complex social groups (see project 2 below). In addition, I hope to begin development of a new technique that will allow for the determination of mating success among cobreeding males by detection of sperm in the perivitelline layer of eggs (see project 1 below).
Proximate mechanisms of sperm competition and skew. The eventual goal will be to determine potential proximate mechanisms by which skew is maintained and paternity determined by genotyping sperm present on the perivitelline membrane of eggs. The idea behind this relatively new technique is to identify the sperm trapped between the ovum’s perivitelline layers as an allelic record of sperm competition close to the time and place of fertilization. It involves the relatively simple procedures of collecting eggs either prior to or immediately after the start of incubation and removing the perivitelline membrane. The technical hurdles involve eliminating the maternal and/or embryonic DNA attached to the membrane that, due to their higher concentration, can potentially confound PCR amplification of the sperm DNA, and matching the remaining DNA to potential sires. In collaboration with Dr. Bart Kempenaers of the Max Planck Institute, I hope to have a student working on refining this technique and overcoming the technical hurdles mentioned above. In the case of acorn woodpeckers, the application of this technique over the next few years offers the opportunity to infer information about the mating history of females that, because copulations are almost never seen, cannot be obtained observationally. This will be particularly valuable in the following contexts: (a) Is sperm from both males in groups with 2 cobreeder males (and a single breeder female) generally present at fertilization, even though almost two-thirds of nests are sired by a single male? If not, then it would suggest that females copulate with only a single male for each clutch, in which case it is plausible that males could adjust their behavior according to copulatory access (e.g. for degree of effort in feeding nestlings) If sperm from both males is generally present, the question remains as to why one of the males is generally so much more successful at gaining paternity and has implications for breeders not knowing actual paternity; (b) Do sperm present differ between sequential nests involving the same coalition of males? If so, this would suggest that females copulate with a different male for each clutch, offering a mechanistic explanation for the observed switching of paternity between successive clutches; (c) In large, complex groups containing 2 joint-nesting females and/or 4+ cobreeder males this technique will be especially informative, particularly when such coalitions include younger sons that appear not to achieve their fair share of paternity (based on previously collected data). d) Do sperm present differ in sequential nests involving the same coalition of males and breeder females? If so, this would suggest that females are not consistent with what males they copulate with, again offering a mechanistic explanation for the observed switching of paternity between successive clutches.
Reproductive partitioning in complex groups. The other students working in my lab will continue to investigate the patterns of reproductive bias in large male coalitions (one student) and among complex social groups containing joint-nesting females and large male coalitions (a second student). While only 12% of groups between 2004 and 2008 involved 3 or more cobreeder males, 27% of breeder males lived in coalitions of 3 or more and are thus important to estimating the direct and indirect fitness benefits of cobreeding. Similarly only 15% of groups contain joint-nesting females, but 23% of breeder females live in coalitions. Preliminary data from the complex social groups suggest that nests produced by joint-nesting females are more likely to be multiply-sired than nests of single females and that there is no difference in the frequency of multiple paternity between nests with small vs. large coalitions of cobreeder males. Both of these patterns will be addressed in these student projects.
Note: Dr. Lefcort accepts students for summer positions only.
This research comes about due to the threat of high levels of carbon dioxide that humans are releasing. Carbon dioxide in water is converted to carbonic acid. Sea water that is more acidic lowers calcium and aragonite saturation states which make it harder for organisms to calcify their shells and skeletons. Most attention has been directed at marine creatures where a 0.1 increase in ocean water acidity since the industrial revolution has been noted. Although this value appears small, the change has occurred 10 times faster than at any time in the last 50 million years.
While much attention has been given to marine systems, CO2 may also affect freshwater aquatic systems. Lake acidification gained attention during periods of worry in the 1980’s over acid rain but few studies have explored the effects of CO2 on aquatic systems.
My lab studies the ecological and behavioral effects of heavy metal pollution on populations of Physella columbiana and Lymnaea palustris aquatic pulmonate snails. I am looking for two students to explore how atmospheric CO2 increases may affect snail ecology. In partial collaboration with Dr. Cleary (Chemistry), my students and I will bubble CO2 into pond water and then look at the effects of acidic water on snail anti-predatory behavior.
Although most of the work will be in the laboratory the students need to be prepared to work outside to gathering snails from the field.
Note: Dr. Poxleitner is not accepting new students for Fall of 2015.
I currently have two projects underway in my lab. The first is using bacteriophage as a biocontrol to fight Crown Gall disease. The second is a bioinformatics project to finish and annotate the genome of a chloroplast from Erythroxylum coca.
Bacteriophages are viruses that infect and kill bacteria. We are isolating phage specific for the bacteria Agrobacterium tumefaciens, which causes Crown Gall Disease in horticultural crops. Each isolated phage is purified and assessed for its ability to control Crown Gall Disease in Solanum lycropersicum (tomato) and Vitis vinifera (grapes) Effective phage will be used to creat a biological control agent for crop plants to reduce economic losses due to the disease.
The second project uses bioinformatics techniques to evaluate the newly sequenced Erythroxylum coca choroplast. This project began by isolating Erythroxylum chloroplasts and sequencing them via Solexa 454 technology. This sequence was finished via Sanger sequencing and the complete genome annotated using common bioinformatics programs. The genome will be compared to other chloroplast genomes in the Order Malpighiales to identify differences. These differences will be used to create more accurate phylogenies describing the evolutionary relationships of the order.
Patients with neurodegenerative diseases such as Huntington's, Alzheimer's, and Parkinson's all show disruption in sleeping patterns called the circadian rhythm. Some initial treatments in Alzheimers's disease are aimed at correcting circadian rhythm and have had some initial success. This and other studies lead to the hypothesis that lack of proper circadian rhythm is part of the progression of a neurodegenerative disease state. By using the fruit fly, Drosophila melanogaster, I am testing if disruptions to circadian rhythm are causal to the disease state of certain neurodegenerative diseases. The fruit fly offers genetic tools both for neurodegenerative diseases and mutants that impact the circadian rhythm. First, genetic crosses would be done to determine how these two interact; future research would include how these pathways interact at the molecular level and to test any pharmacological agents that may effect these pathways. Ultimately the goal of the research is to identify potential treatments that would limit or slow the progression of these neurodegenerative diseases.
Contact Dr. Smith
Salamanders communicate via pheromones. My research focuses on understanding the structure, function, and evolution of pheromone-producing glands. Salamanders are known for their moist glandular skin, yet little is known about which glands actually produce pheromones other than the well-studied courtship glands on the male chin (known as the mental gland). While pheromones from the mental gland have been well studied, little is know about the pheromones that females produce or about the pheromones that males produce from non-mental glands sources. Interestingly, males of some species lack the pheromone-producing mental gland that is supposedly so important for courtship. Do they produce pheromones from other glands? While the mental gland is known to be controlled by androgens, little is known about the control of other glands. Our current projects focus on understanding androgen control of pheromone production in non-mental glands.
Using immunohistochemistry, we will address questions such as:
1) Which glands have receptors for androgens?
2) Is there sexual dimorphism in androgenic control of modified granular glands?
3) How does androgen receptor distribution vary between different types of skin glands? Specifically, are the putative courtship glands the only glands with androgen receptors?
The Swanson Lab studies how complex mechanical systems evolve in animals. Specific current projects include: a study of the swimming performance costs of sexually selected male ornamentation in sword-tail fish, a study of the microstructure and impressive material properties in crustaceans, and a study of the effects of heavy metal pollution on fish feeding and swimming performance. Research students are involved in experimental design, data collection (in the field and in the lab), data analysis and presentations.
My research and each project below is focused on developing informatics tools and approaches related to ecology and biodiversity data discovery and integration.
In collaboration with UC Davis and Arizona State University, we are developing approaches for describing and reasoning over alignments between biological and phylogenetic taxonomies. We have developed a set of tools (collectively called Euler) for describing mappings between two taxonomies and then determining whether the result "makes sense" (is consistent) and if so, to compute the resulting taxonomy induced by the alignment. Given this, there is still a need for developing meaningful visualizations of the resulting taxonomies, developing approaches for explaining (and visualizing) why an alignment is inconsistent (as well as why the alignment produced a certain result), benchmarking different algorithms/tools for performing the alignment, and optimizing the underlying alignment algorithms. Other topics for potential student projects include looking at standard taxonomy revision techniques ("splitting" and "lumping") as well as specific properties of phylogenetic trees to enhance the alignment approach.
Another area for student projects concerns automating the development of ontologies for annotating ecological data sets. This work is in collaboration with UC Santa Barbara (NCEAS) through a variety of ongoing informatics projects to support ecology data management. Ontologies provide structured and controlled vocabularies for describing data sets and can be used to improve the precision and recall of data discovery queries. As an earlier pilot project, we developed a set of scripts to automatically extract and analyze relevant terms from a corpus of ecology papers. We would like to further analyze the results and extend the approach to find richer relationships between terms (which can further improve precision and recall). For example, it may be possible to use co-occurrence or other standard information retrieval approaches to discover relationships among terms. Another approach would be to look at external sources that already provide some term relationships (such as GBIF or WordNet) to "seed" relationships and discover new ones. A similar project would be to extend the approach to consider a wider range of information sources, including ecology metadata repositories (such as the KNB).
The research work described above will involve computer programming skills, primarily focused on developing and running basic scripts (in Python or R) to carry out experiments and to implement relevant tasks. It is anticipated that students will learn a variety of new skills as part of each of the above projects. Students will also potentially collaborate with computer science students working on related topics.
Methanogenic archaea are microorganisms that make a living by converting carbon dioxide (CO2) to methane (CH4). These organisms, known as methanogens for short, can amazingly use CO2 as their sole source of both energy and carbon to make essential biomolecules such as proteins and DNA. Although you cannot see them, methanogens are present in almost every anaerobic (no oxygen) environment, from the rumen of cattle and intestines of humans to deep-sea hydrothermal vents and freshwater lake sediments. Collectively, methanogens generate over 400 million tons of methane each year as an essential component of the global carbon cycle. Although carbon dioxide is the most abundant greenhouse gas, methane is ~25X more efficient at absorbing the infrared radiation that is responsible for observed climate change, and thus is a more potent greenhouse gas than carbon dioxide. Therefore, the production and consumption of methane is of intense and increasing environmental interest. Additionally, the bioconversion of methane to liquid fuel and hydrogen gas and/or the use of microbes involved in methane metabolism for biofuel production is an attractive solution for alternative energy requirements. To this end, research in the lab is centered on the unusual enzymes and coenzymes required for methane production and consumption in anaerobic environments.
Current projects include: (1) culturing methanogens under various experimental conditions to analyze the distribution of modified coenzymes involved in yet-to-be discovered processes, (2) anaerobic protein purification to identify the proteins with which modified coenzymes are associated, and (3) anaerobic enzyme assays to uncover functions of currently unknown enzymes and coenzymes important for methanogenesis and reverse methanogenesis. Most of the work must be carried out under strictly anaerobic conditions, giving students unique research experience. Students with interests in biochemistry and/or microbiology would be a great fit for the lab.
New lanthanide thiophosphates. Lanthanide thiophosphates present interesting extended inorganic structures. They also have potential applications in the development of new radiation detectors and nonlinear optical materials. In our lab, we have synthesized and characterized a number of these compounds and work continues in this area. Students working in this area learn glassblowing, high temperature crystal growth, spectroscopy, and x-ray diffraction.
New lithium batteries. We have developed some new materials that have shown promise as electrodes for new lithium batteries. We focus on electrodes that can be produced from inexpensive starting materials and that are lightweight. Students working in this area learn electrochemistry, cell construction, and aqueous metal ion chemistry.
Thin films. Many of the materials produced in our lab will be of more practical use if they can be fabricated into thin films. Hence, we have a line of research dedicated to producing thin films of the compounds synthesized in our lab. The end use of such films would be as optical components and chemical sensors.
Photoelectrolysis of water. In collaboration with researchers at several other colleges and universities, we are examining a series of metal oxides looking for those which catalyze the reaction 2H2O(l) 2H2 (g)+ O2(g) in the presence of sunlight. Students working on this project would learn about combinatorial chemistry, lasers, photochemistry, and computer interfacing.
Contact Dr. Cleary
Like serotonin, neuropeptides are signaling molecules within the brain and gastrointestinal tract. Problems with signaling often cause health problems. Despite the prevalence of neuropeptides within the brain and their importance, they are often poorly characterized under physiological conditions. Our research aims to provide key structural characteristics of neuropeptides under physiological conditions for the sake of aiding the rational design of therapeutics.
Neuropeptides are found within neural tissue and bind to transmembrane G-protein coupled receptors (GPCRs). A given neuropeptide may interact with multiple receptors, each inducing unique effects within the nervous system. That they function as ligands to GPCRs, despite their often unstructured or only partially structured nature, is impressive. Whether or not the partially structured site displays a recognition motif is an open question. Directly identifying the functionally important characteristics of a given neuropeptide has been difficult because under physiological conditions they are primarily unstructured, which makes it rather challenging to obtain structural information for rationally designing therapeutics.
This research will target neuropeptides where a fundamental structural question relates to the cis-trans isomerization of an amino acid (proline). For example, under physiological conditions, endomorphin structural characteristics are unknown, and cis-trans proline isomerization might play an important role in receptor binding. Site-specific carbon-deuterium (C-D) labeled neuropeptides will be synthesized by solid-phase peptide synthesis and undergo spectroscopic characterization (IR, circular dichroism, and NMR). The insights gained from these studies will help unravel the complex nature of neuropeptide structure and specificity, which would ideally translate into more facile design of highly selective agonists and antagonists.
The carbonic anhydrases (CAs) catalyze a reaction of fundamental biochemical and physiological importance, the interconversion of carbon dioxide and bicarbonate ion
All CAs are zinc-dependent enzymes and a well-established mechanistic paradigm requires the coordination of substrate to the catalytic zinc ion (Zn2+). The structures determined for the b class carbonic anhydrases (β-CAs), common in plants and bacteria, generally fall into two distinct subclasses based on the observed coordination of zinc. One subclass of β-CAs coordinate Zn2+ tetrahedrally with four protein-derived ligands, and in this configuration access of substrate to the zinc coordination sphere is apparently blocked. The ability of substrate to coordinate to zinc is observed in the other structural subclass. The available evidence supports the hypothesis that the blocked configuration, as seen for example in ECCA, a β-CA from Escherichia coli, represents an inactive conformation of the enzyme, and that all such β-CAs can undergo a transition to an active conformation. In addition, a unique, non-catalytic binding mode for the substrate bicarbonate was discovered in ECCA that appears to stabilize the blocked, inactive form of the enzyme and seems to represent a regulatory mechanism.
This project specifically aims to characterize the allosteric bicarbonate site that is likely shared by many eubacterial β-CAs, including a number of pathogens (e.g., Mycobacterium tuberculosis, Salmonella typhimurium). The structural and functional effects of its disruption by targeted mutagenesis are to be investigated by the primary method of X-ray crystallography, supported by kinetic measurements. In view of its potential as a site for therapeutic intervention, the characterization of the allosteric site will be furthered, in collaboration with Stephen Warren and coworkers, by a virtual screen for potential non-substrate ligands and subsequent determination by crystallography of the structures of the binary complexes. Finally, the relationship between allosteric bicarbonate binding and the hypothesized structural transition in ECCA will be probed by testing the effects of mutations designed to shift the conformational equilibrium, The two observed structural subclasses serve as an explicit two-state model for regulation. This project will be attractive to students with interest in biochemistry, particularly protein structure and enzymology. It integrates a textbook example of an extremely fast enzyme with allosteric regulation of enzyme activity. The project also emphasizes computational methods, including molecular graphics, modeling, and informatic methods of drug discovery.
A second project that is getting underway is a systems biology investigation of the effects of β-CA knockouts or attenuation of enzyme activity on metabolic flux and expression profiles in prokaryotic cells. The substrates of carbonic anhydrase are hubs in a metabolic network, and limitation of the rate of CO2/HCO3- interconversion is likely to have significant effects on a number of cellular systems. Existing methods of metabolic modeling, such as flux balance analysis, will be applied to these systems to predict the effects of loss of CA activity, and eventual comparison with systems data obtained for wild-type and knockout strains. The development of inhibitors, the goal of the first project, will in principle allow titration of CA activity, in order to examine the effects of varying levels of CA activity on the systems properties of the affected cells. This project will be mainly computational and curational in its early stages, and will be blended with experimental data as progress permits.
Biomedical Imaging allows the non-invasive interrogation of biological processes at the cellular and molecular level. The information acquired through imaging can enhance our understanding of disease mechanisms and could potentially aid earlier detection of diseases and evaluation of treatments. The general focus of research in my lab is on the development of new imaging agents for cancer and neuroimaging. There are three current projects available for students to participate in. All projects span inorganic, synthetic, analytical, and biochemistry areas and would therefore introduce undergraduates at any level to the interdisciplinary nature of research. Students will learn to design and synthesize new organic compounds and inorganic coordination complexes. They will also have the opportunity to learn how to prepare liposomes and micelles, and acquire expertise with common analytical techniques such as NMR, HPLC, LC-MS, and UV-Vis.
Project 1: Metal-ion responsive imaging agents for cancer and neuroimaging
Metal ions play critical roles in a host of fundamental biological processes; however improper regulation of metal ion stores is also connected to acute and long-term diseases including cancer, diabetes, heart disease, and neurodegeneration. The non-invasive monitoring of changes in the levels of metal ions may therefore facilitate the diagnosis of diseases and optimization of treatment. In this project, new metal-ligand complexes that alter their properties in response to the presence of Zn2+, Ca2+, Fe2+, and Cu2+ will be designed, synthesized, and characterized. Their imaging properties will also be investigated in vitro, and eventually, in various disease models.
Project 2: Dual-modality MRI and optical Imaging agents for monitoring drug delivery in cancer
Despite significant advancements in the fight against cancer, it still remains a challenging medical problem. The utility and effectiveness of systemic chemotherapy, the most common approach to the chronic management of cancer patients, is limited by significant toxicity to non-cancerous cells. To overcome this limitation, research efforts have been focused on the development of drug delivery systems that facilitate concentrated and targeted delivery of specific drugs and other agents to the tumor with the aim of increasing the therapeutic ratio and minimizing toxicity to healthy cells. This project will focus on the development of nano-vesicles comprising lanthanide complexes and organic chromophores. These nano-vesicles will be fully characterized using a range of analytical techniques and their surfaces will be modified with tumor targeting groups.
Project 3: Brain-penetrant metal complexes for neuroimaging
The increasing incidence of neurodegenerative and mental health disorders has prompted the need for more tools to assess brain function. Positron Emission Tomography (PET), is a promising imaging technique that combines high sensitivity and excellent signal-to-background ratio. PET imaging agents can be produced and administered in very low concentrations and this allows interrogation of biochemical processes at the molecular level without prompting a pharmacological effect. The majority of PET imaging agents developed for neuroimaging incorporate the radioisotopes 11C, and 18F, which require the availability of expensive, and poorly accessible, cyclotron infrastructure. The aim of this project is to address this issue by developing lipophilic radiometal-based neuroimaging agents that incorporate cheaper and easily accessible radioisotopes such as 68Ga. The central hypothesis is that the lipophilicity of these compounds will facilitate their delivery across the blood-brain-barrier.
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With recent advances in the computational resources available to chemists, computational methods that describe the motion of the electrons in atoms and molecules (aka electronic structure methods) have become an increasingly useful tool for understanding/interpreting molecular properties as well as the energetics and dynamics of reactions. Nonetheless, to establish electronic structure theory as a truly predictive tool in chemistry, the development of more accurate and cost-effective methods is desirable. Research in our group aims to address this goal on two fronts. Recently, we have been able to reduce the computational cost of existing models (without a significant loss in accuracy) by developing a systematic procedure for the construction of natural orbitals. In conjunction with collaborators at Argonne National Laboratory, we are also actively pursuing the development of the Graphically Contracted Function approach for electronic structure theory; this method, although still in its infancy, has the potential to significantly improve the cost-effectiveness and accuracy of current state-of-the-art computational models.
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Our research involves developing materials and methodologies for chromatographic analysis of adsorption, binding, and partition events at lipid bilayers. Such interactions can, among other things, influence a drug’s activity and toxicity, affect the activity of membrane proteins, and determine the bioaccumulation of environmental chemicals. Furthermore, lipid bilayers are integral components in many biosensing and liposome-based delivery strategies and the characterization of solute adsorption behavior is crucial to the development and application of these technologies. In general, high performance affinity chromatography (HPAC) techniques seek to relate the retention of a substance on a packed column to the strength of its specific interaction between the stationary and mobile phases of the column. In principle, this approach to characterizing bioaffinity interactions can offer a number of analytical advantages over other techniques; however it does require the establishment of stable and immobilized biological “films” or “layers” on micro-particulate materials to serve as the stationary phases. The lack of such materials has been a significant impediment to the application of HPAC to biomembrane interactions.
Recent work in our lab has produced materials and methods for assembling lipid bilayers on nanometer-scale silica colloids which we are now using to create lipid bilayer-based stationary phases for liquid chromatography. Preliminary results with the materials are very promising, particularly with respect to evaluating weak and moderate affinity interactions such as those between metal ions and ionophore receptors and channels. Low affinity interactions are particularly difficult to analyze by other techniques and thus the development of materials and methodology that can reliably do so may have particularly broad impact in the field.
Ongoing development of the lipid-silica materials and their application in studies of membrane interactions are the current foci of our research. Projects are available that pertain to the biophysical characterization of lipid bilayers supported within porous silica particles, developing thin organic films for the purpose of affecting lipid-particle interactions, assembling and characterizing new capillary chromatography instrumentation configurations with new pumps and detectors, and chromatographically analyzing molecular interactions with lipid bilayers.
Dr. Shepherd’s research seeks to elucidate the biosynthetic pathway of rhodoquinone (RQ, 1 in Figure 1) which will later be used as a target for the development of new anti-parasitic drugs. RQ is an essential electron carrier used in the anaerobic energy metabolism of species such as the parasitic helminths, the free-living nematode Caenorhabditis elegans (C. elegans), and the purple non-sulfur bacterium, Rhodospirillum rubrum (R. rubrum). RQ is not synthesized or used in humans and other mammals with a primarily aerobic energy metabolism. However, RQ is structurally similar to ubiquinone (coenzyme Q or Q, 2 in Figure 1), an important lipid component involved in electron transport in the aerobic respiratory chain, and the biosynthetic pathways of RQ and Q are proposed to be similar. The biosynthesis of Q has been well-characterized in both prokaryotic and eukaryotic species.
It has recently been shown by Dr. Shepherd’s laboratory that catabolism of Q is required for RQ biosynthesis in R. rubrum. A mutant strain (F11) of R. rubrum has also been identified which can synthesize Q, but not RQ, and therefore cannot grow anaerobically. After sequencing the whole genome of F11, and a spontaneous revertant (RF111), we identified a new gene, rquA, which is the first known gene required for RQ biosynthesis. We are currently working on the expression, purification and characterization of the gene product (RquA). Using bioinformatics and RNA sequencing data, we have also identified four new candidate genes that may be involved in RQ biosynthesis in R. rubrum. We are in the process of preparing gene knock-out mutants to determine the necessity of these genes for RQ biosynthesis. In addition, we have begun work with the C. elegans worm model using RNAi gene knock-downs to identify further candidates required in the RQ biosynthetic pathway. Characterization and regulation of unique enzymes in the RQ biosynthetic pathway will provide a novel target for antihelminthic drug discovery.
Figure 1. Schematic representation of potential ways RquA acts in the biosynthesis of RQ. Pathway A represents the methylation of DMeQ to form a pool of Q reserved for the biosynthesis of RQ. Pathway B represents a complex in which RquA acts in conjunction with other enzymes to act as an amidotransferase to substitute Q’s methoxy group with an amino group on RQ
According to the most recent assessment by the World Health Organization, 884 million people around the world lack access to “improved water supply” and more than 2.5 billion lack access to “improved sanitation”. The health consequences of inadequate access to improved water and sanitation include an estimated 4 billion cases of diarrhea and 1.6 million deaths each year, mostly among young children in developing countries. My projects involve the development and optimization of sustainable, household water treatments for the removal of biological pathogens and naturally occurring inorganic contaminants such as arsenic and fluoride.
I am looking for a student to determine whether or not charred cow bone will effectively remove fluoride ions from natural waters.
The world, especially the industrialized world, is facing two emerging epidemics. These epidemics will create significant medical needs that will negatively impact health care systems and the economies of the world if a proactive approach is not taken towards new solutions. One of these emerging epidemics is Type 2 Diabetes which is impacting a growing percent of our population. The other epidemic is the result of the steady increase in the average age of the population world wide (which is projected to continue) coupled to the exponential link between increasing age and the incidence of neurodegenerative disease. Biochemical changes in the metabolism of cell types involved in both of these diseases have been noted.
Lactate has been considered a dead-end waste product of anaerobic metabolism since the 1930's. However, new evidence has emerged showing that lactate is an important energy source that is shuttled between cells and throughout the body. Lactate is being shown to play an important role in muscle and brain metabolism, with the associated implications for diseases in which these tissues form an important component. Muscle metabolism and its alteration have large implications in Type 2 Diabetes. Biochemical changes in the metabolism of the heart muscle are also implicated in congestive heart failure.
In brain metabolism, glucose has traditionally been thought to be the exclusive energy source. However, new hypotheses are emerging that the preferred energy substrate for neurons is not glucose but may instead be lactate. This has wide implications for the study of brain function and diseases as monitored by energy usage. For example, in Alzheimer's disease it has been reported that metabolic deficits often precede the appearance of first symptoms. A probe that could monitor the Krebs cycle could give early indication of decrease in neuronal metabolic activity and neuronal death. This could be an invaluable research tool and diagnostic for neurodegenerative diseases including Alzheimer's and Parkinson's disease.
A specific aim of this research is to develop a probe that monitors lactate's function as an energy substrate while minimizing the number of assumptions and measurements needed to account for the other activities of the molecule and its metabolites. The goal is to monitor some of lactate's functions, but not all of them. To this end lactate analogs have been selected and will be synthesized and evaluated based on their potential for being trapped in the Krebs cycle where it is likely that rate and/or amount of accumulation can be correlated to the rate of activity for the cycle, thus providing a diagnostic indicator for many diseases where energy usage is altered. While currently there is no direct way to monitor aerobic metabolism in vivo at the cellular level,these analogs have this potential when developed as Positron Emission Tomography probes. This is timely and critical research that could advance our understanding of the diagnosis and treatment of energy dependent diseases.
I am looking for a motivated independent student to evaluate lactate analogs for their lactate dehydrogenase activity.
The Watson lab studies the enzyme HMG-CoA reductase and its role in the physiology and pathogenesis of the bacterium Burkholderia cenocepacia, an opportunistic lung pathogen that is naturally resistant to most known antibiotics and a major cause of fatality in cystic fibrosis patients. There are many unusual aspects of this enzyme, from its fundamental biochemistry to its evolutionary history, that suggest it may be a highly regulated enzyme in the bacterium and therefore maybe a new target for future antibiotics. We employ protein chemistry, spectroscopy, molecular biology and bioinformatics techniques to understand the molecular mechanisms by which this unusual enzyme performs its function.
Primary projects include: enzyme kinetics, fluorescence spectroscopy and circular dichroism spectroscopy under changing conditions of pH, enzyme concentration and substrate concentration to identify key structural changes in the enzyme; site-directed mutagenesis of potentially key amino acids in the structure and function of the enzyme and characterization of the mutant enzymes; bioinformatics and evolutionary studies of a newly identified class of bacterial HMG-CoA reductases; generation of plasmid vectors for HMGR gene knockouts in Burkholderia cenocepacia. Students typically have completed at least CHEM 331 and BIOL 105-106 before joining the lab, but exceptions can be made.
My research is on the Primordial Helium Abundance. The focus is on determining the amount of helium produced in the very early universe (3 minutes after the Big Bang) by analyzing the spectral emissions of dwarf galaxies. In addition to an introduction to Astrophysics and Cosmology, the research involves widely applicable skills such as computer programming, statistical analysis, and model evaluation. Beyond an eagerness to learn, no prior experience in any of those areas is required.
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