Research in the Biology and Chemistry/Biochemistry Departments at Gonzaga University covers a wide range of topics at the cutting edge of science, not just in the traditional definitions of the disciplines, but at the interface of biology and chemistry as well.  Below you will find short descriptions of the individual research interests and/or available projects in faculty labs in the two departments.  If you are interested in any of these projects, or even if you simply have questions, please contact the faculty member directly.  If a particular faculty member is not listed below, you can often find information about their research interests at the Biology or Chemistry and Biochemistry department web pages.

For more independent research opportunities, check out our neighbors across the river, the WWAMI Medical Education Program.  Research faculty at WWAMI may have openings in their labs for Gonzaga undergraduates.  Please see the descriptions of their research below. 
If you have any questions, please see Christy Watson or contact the WWAMI faculty directly.

If your research will make use of the Gonzaga Greenhouse, you will find more information here.

Spring 2010 URA Positions

For students interested in applying for an HHMI Undergraduate Research Assistant position, check the specific laboratory below to make sure there is an open position.  If you are still interested in applying, fill out the application on the Undergraduate Research Main page.

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.

Biology Faculty:

Kirk Anders: eukaryotic genetics using yeast as a model organism

Julie Beckstead: interactions between invasive plant species and seed pathogens

Mia Bertagnolli:  cell adhesion and migration during tumorigenesis

David Boose:  genetic diversity

Gary Chang:  consumer-resource interactions and biological control

Seth Coleman:  behavioral ecology and disease dynamics in freshwater fishes

Bill Ettinger:  regulating photosynthetic carbon fixation

Joey Haydock:  reproductive partitioning in the cooperatively breeding acorn woodpecker

Hugh Lefcort: predator/prey relations in aquatic snails

Marianne Poxleitner: evolution of cocaine biosynthesis

Robert Prusch:  cellular mechanisms of endocytosis

John Shea, S.J.: parasite-altered behavior of hosts and parasites as indicators of ecosystem health

Nancy Staub: salamander evolutionary biology

Brook Swanson: evolution of complex mechanical systems in animals

Chemistry and Biochemistry Faculty

Matt Cremeens: neuropeptides: neuroscience for the organic chemist

Jeff Cronk:  enzymatic and structural studies of β-carbonic anhydrase

Eric Ross: development of porous nanomaterials for bioanalytical applications

Jennifer Shepherd: rhodoquinone biosynthesis in parasitic helminths

Tommaso Vannelli: synthesis of compounds for photodynamic therapy of cancer

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

WWAMI Faculty

Kenneth Roberts:  sperm maturation, function and fertilization with application to male infertility and contraception

Weihang Chai:  cellular and molecular mechanisms behind the growth of cancer cells, especially the mechanism that regulates telomeres

Leventa Kapás:   humoral/hormonal regulation of sleep in rodent models

Éva Szentirmai:   the links between sleep and metabolism

Jonathan Wisor:  neurobiological basis for sleep, biological rhythms, and sleep disorders therapeutics

 

Research In Biology

Research in the Anders Lab

I am interested in genes, chromosomes, and genomes: how they contribute to the traits of an organism, how they are transmitted during cell division, and how they can change from generation to generation. My research makes use of the brewer’s yeast Saccharomyces cerevisiae as a model eukaryotic organism. My students and I are working to understand how a common mistake in cell division–resulting in an extra chromosome–affects phenotype, genome stability, and ultimately, fitness. We are currently studying the effects of duplicating the small chromosome 6. We discovered that an extra copy of chromosome 6 prevents viability, and that an imbalance in tubulin expression may be one significant cause. We suspect that there may be additional gene dose imbalances that interfere with other cell functions when chromosome 6 is duplicated. Our current goal is to discover and characterize the other significant dose imbalances at the molecular level. We use a variety of methods, including recombinant DNA techniques, microbial genetics, and whole-genome microarrays.

Positions available in spring 2010:

Project #1
When cells make mistakes in cell division, they can gain or lose chromosomes, generating a state called aneuploidy. Aneuploidy is typically detrimental to cells, not because genes have been mutated, but because it creates an imbalance in the "dose" of certain gene products relative to others. (Down Syndrome is a well-known human aneuploidy.) In order to begin to understand the specific molecular connection between chromosome number and phenotype, we are studying a specific chromosomal aneuploidy in yeast that leads to inviability: two copies of chromosome 6 in an otherwise haploid cell. We are testing the following hypothesis in a variety of ways: the beta-tubulin gene on chromosome 6 is responsible for the inviability of aneuploid 6, but it is not the only gene that contributes to the detrimental phenotype of aneuploid 6. The experiments that will be done this fall are to complete the construction of yeast strains that (1) have deleted beta-tubulin from chromosome 6 or (2) have inserted an alpha-tubulin into chromosome 6, induce these strains to duplicate chromosome 6, characterize the resulting phenotypes, and use microarray comparative genomic hybridization to determine the copy numbers of the chromosomes in the resulting cells. Based on preliminary observations using a different method, we anticipate that we may observe interesting phenotypes, including a potentially unstable genetic phenotype that gains additional chromosomes.

For a review of aneuploidy, see http://www.genetics.org/cgi/content/full/179/2/737
For a description of our experimental system, see http://www.biomedcentral.com/1471-2156/10/36
For a summary of our research program, see http://gonzology.gonzaga.edu/~anders/

Project #2
The most abundant forms of life in the biosphere are the viruses that infect bacteria, called bacteriophages. Bacteriophages carry genomes that are quite diverse genetically, even those that infect the same species of bacterium. It is therefore of interest to discover and characterize new bacteriophages to learn more about the genomic diversity of these life forms. One practical implication of this new knowledge is the possibility of using phages to fight bacterial infections, particularly in cases where the bacteria are resistant to all known antibiotics. This project is aimed at finding new bacteriophages in the environment in order to decode their DNA. The student will learn how to cultivate the soil bacterium Mycobacterium smegmatis (a harmless bacterium related to M. tuberculosis), and will learn how to infect the bacteria with phage, then will gather and test a variety of soil samples from the Spokane region for the presence of mycobacteriophage. Once found, these phage will be purified, amplified, and DNA will be isolated for cloning and sequencing.

For a description of mycobacteriophage genomics, see http://dx.plos.org/10.1371%2Fjournal.pgen.0020092 

Contact Dr. Anders
Get more information about the Anders Lab

Research in the Beckstead Lab

My current research focuses on exploring the interactions between invasive plant species and their enemies, specifically seed pathogens. I am looking for motivated students to work together on lab-related ecology projects. We will critically examine the ecological and evolutionary relations of an invasive plant, cheatgrass (Bromus tectorum), and a new enemy to cheatgrass, a fungal pathogen (Pyrenophora semeniperda) that kills cheatgrass seeds in the seed bank. Through laboratory experiments, this research will test hypotheses exploring how cheatgrass copes with this new pathogen through germination strategies to out-compete the pathogen for seed resources.  Secondly, this research investigates the community level consequences of this new plant-pathogen relationship on the co-occurring native species and the implications for restoration of cheatgrass-infested land. The research work will involve basic microbiology skills (aseptic techniques, making various types of agars, isolation of fungus, and inoculation experiments) as well as fieldwork involving collection of seeds from different invaded sites in eastern Washington. Preference will be given to students who have completed BIOL 102 and BIOL 202. Students interested in working for salary or a combination of salary and research credit should contact Dr. Beckstead.

Position available in spring 2010:

My current research focuses on exploring the interactions between invasive plant species and their enemies, specifically seed pathogens.  At this time, I have a seed pathogen that can kill the seeds of the problematic and invasive cheatgrass plant.  We are investigating this fungus as a biological control.  I am looking for a motivated student to work on a lab-related ecology project that would 1) investigate the storage conditions that will enable the fungal inoculum to retain its viability and 2) explore how the seed size of an infected seed determines the fungus’ ability to infected adjacent seeds.  This seed pathogen-cheatgrass system is a great system for students to design their own research projects. The research work will involve basic microbiology skills (aseptic techniques, making various types of agars, isolation of fungus, and inoculation experiments) as well as seed germination experiments.  Preference will be given to students who have completed BIOL 102 and are now enrolled in or completed BIOL 201.  Please contact Dr. Beckstead, if you have an interest in working on this project.

Listen to Dr. Beckstead describe her research on Northwest Public Radio.

Contact Dr. Beckstead
Get more information about the Beckstead Lab

Research in the Bertagnolli Lab

As a cell biologist, I am interested in cell adhesion and migration, and how these processes are altered during tumorigenesis. Many individuals with colon cancer have mutations in the Adenomatous Polyposis Coli (APC) gene, which can result in a truncated form of the APC protein. It has been shown that APC is important in regulating cytoskeletal structures. Mutations in the APC gene therefore affect cell adhesion and migration, both of which are cytoskeleton-dependent. To learn more about the role of APC in these important cellular functions, we have developed an in vitro system in which we express mutated APC in cultured epithelial cells. By wounding sheets of epithelial cells and monitoring the rate of wound closure, we can compare migration rates in normal cells and cells expressing the truncated form of the gene. In addition we are looking at the effects of truncated APC on the activity of Rac and Rho, small GTP binding proteins that are known to be important regulators of cytoskeletal function. These studies should help increase our understanding of the role of APC both under normal conditions and during the alterations that occur in tumorogenesis. 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.

Position available in spring 2010:

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.

Contact Dr. Bertagnolli
Get more information about the Bertagnolli Lab

Research in the Boose Lab

The general topic of my research is genetic diversity in natural populations, and what it tells us about ecological and evolutionary processes. My primary research project is a collaboration with Dr. Julie Beckstead and colleagues in Utah, studying Pyrenophora semeniperda, a fungus that infects the seeds of native and introduced grasses in the western U.S. The fungus, known by its fans as “Black Fingers of Death” for the distinctive black reproductive structures it makes, is a potential biocontrol agent for cheatgrass (Bromus tectorum), a highly invasive annual grass.
As part of this effort, I have been examining genetic variation in samples of the fungus from across the Intermountain West. I am also working with students who are studying samples of the fungus isolated from host plants other than cheatgrass, in an effort to see if the fungus specializes on host species in any way.

A second project on which I have been working for some time looks at genetic diversity in plants that inhabit ephemeral wetlands known as vernal pools. Vernal pools are shallow depressions that fill with water in the spring and become completely dry by the early summer. The animals and plants that live in vernal pools have evolved life cycles and other adaptations that allow them to survive this drastic change in conditions. As a result, many of the plants and animals that live in vernal pools are found only in vernal pools.
I'm looking at one particular group of vernal pool plants in the genus Navarretia, which includes about a dozen species and subspecies in vernal pools and other ephemeral wetlands throughout the western United States. The goal of the research is to understand patterns of relatedness among different populations, subspecies, and species, in order to generate hypotheses about how the group evolved and spread to its current range.
All of the projects in which I am involved use molecular genetic markers of some sort. Generally, I use either direct sequencing of regions of the DNA, or highly variable markers known as microsatellites. The projects involve isolating DNA, optimizing the techniques for applying the different markers, generating the data (e.g., doing the DNA sequencing), and then analyzing the data. Most of the work is in the lab, with a few opportunities to get out in the field and see the study organisms in their natural habitat. Students wishing to work on these projects should have a solid background in genetics and evolution, and some experience with the laboratory techniques involved (PCR, gel electrophoresis).

Contact Dr. Boose
Get more information about the Boose Lab

Research in the Chang Lab

My research examines the role of insects as consumers in ecosystems and the factors that affect their impact. Understanding the factors that influence the amount of resources that insects consume can improve our ability to manage pest insects and weeds. I am working primarily on the ecology and natural history of two different insect-based systems. One is the two-spotted lady beetle, which is a predator of aphids and in turn is a host to a sexually transmitted parasitic mite. The second system involves an herbivorous weevil that has been introduced into the United States as a biological control agent of Dalmatian toadflax

Position available in spring 2010:

Practitioners of biological control are interested in factors that can increase the strength of consumer-resource interactions. In the case of weed biocontrol, the timing of developmental events can be important in determining the impact of herbivores on plants. I am seeking a student who will conduct an experiment on the effects of temperature on the growth and development of Dalmatian toadflax, a weed that is common in Spokane. During the fall and/or spring semesters, we will use two controlled-environment chambers to manipulate the temperature at which toadflax seeds are germinated and plants are grown. We will measure the effect of different temperatures on the time required for toadflax plants to reach various developmental milestones in the growth of the toadflax, such as the number of days to germination, first flowering, and first fruits. We will also measure phenotypic traits such as number, height, and diameter of toadflax stems. Ideally, any student working with me will also learn to perform quantitative analyses using R statistical software. The work conducted during the semester will relate directly to field experiments that will be conducted during the next summer on Dalmatian toadflax and herbivorous insects.

Contact Dr. Chang
Get more information on the Chang Lab

Research in the Coleman Lab

My primary research program is based on a remarkable natural hybrid zone between the swordtail fishes Xiphophorus birchmanni and X. malinche in the Sierra Madre Oriental of Mexico, and has three major foci:
(1) The evolutionary divergence of communication systems used in mate choice.
2) Female cognition, mate assessment strategies, and the evolution of male displays.
(3) The ecological and evolutionary dynamics between environmental stress, inducible molecular defenses, and tumorigenesis.
In addition to these three research foci, I intend to develop a local research program investigating sensory, cognitive and behavioral ecology in the brook stickleback (Culaea inconstans) at Turnbull National Wildlife Refuge.

Positions available in spring 2010:

Effective control of invasive species requires understanding their population biology, which can be achieved through population genetic studies. Analyses of population genetic variation in invasive species can provide information on the history of the invasions, breeding systems, and gene flow patterns.  Moreover, population genetic studies of newly-introduced invasive species can tell us much about rates of genetic divergence among populations – a central issue in understanding the process of reproductive isolation and speciation.  This research project will investigate the population genetics between native and introduced populations of the brook stickleback (Culaea inconstans).

Dr. Coleman also has some expertise in the area of pigeon wing-beat sounds.  Read more about it in a recent article by Discovery.com.

Contact Dr. Coleman
Get more information on the Coleman Lab

Research in the Ettinger Lab

Several different lines of evidence suggest that changes in calcium concentration in the chloroplast may have a role in regulating photosynthetic carbon fixation (dark reactions). To test this theory, Dr. Ettinger is in the process of measuring the levels of calcium inside different compartments of the plant chloroplast. Many different ion selective electrodes or fluorescent metal binding dyes lack the ability to effectively discriminate between calcium and magnesium ions. The calcium sensitive biolumenescent protein aequorin has been routinely used to measure calcium in biological systems. The protein emits photons in proportion to the calcium activity in solution. A recombinant DNA vector (pMAQ6) has been developed that directs the expression of aequorin in the plant chloroplast stroma. Dr. Ettinger and his students are transforming common wall cress Arabidopsis thaliana with pMAQ6 with the hopes of measuring calcium concentrations in the chloroplast stroma, and is developing other vectors to direct the expression of aequorin and direct its alternate localization to the thylakoid lumen and the plant cytosol. This research requires skills developed in quantitative analysis (CHEM310, or CHEM240), and genetics and evolution (BIOL202) or molecular biology.

Positions available in spring 2010:

My students will be working on our project to measure Ca²⁺ concentrations in living plant chloroplasts.  We are using calcium-sensitive proteins as in-vivo probes of calcium concentrations. One such probe, Aequorin is a bioluminescent protein that luminesces in direct proportion to the amount of calcium present in solution. My collaborator, Carl Johnson, previously created an RBCS:aequorin construct to study calcium concentrations in the chloroplast stroma. Last summer my students modified Dr. Johnson’s vector to create two thylakoid-localized versions of Aequorin; one with an OE23 transit peptide, and the other with an OE17 transit peptide. The OE23:Aequorin and OE17:Aequorin chimeric genes have been successfully transformed into Arabidopsis thaliana plants. We have performed subcellular localization studies on the transgenic plants and have demonstrated that the plant transformed with the OE23:Aequorin construct is expressing Aequorin and localizing the protein to the thylakoid. We need to do further studies to assess the localization of the OE17:Aequorin protein product. Furthermore, many of the localization studies have been performed on Tobacco plants. We greatly desire to create transgenic tobacco plants using our vectors. This would enable us to perform much more comparative studies.
Another Calcium-sensitive protein probe we are working on is YC3.6, which is calcium-sensitive fluorescent protein. We have designed vectors that should express YC3.6 in plant cells and target the protein selectively to the chloroplast stroma using a transit peptide from the small subunit of Rubisco (RBCS), or to the thylakoid lumen using the transit peptides from either OE17 or OE23. The RBCS:YC3.6 construct was recently created and we are attempting to transform Arabidopsis thaliana plants with that construct. My students will also be working on cloning the YC3.6 gene into an E.coli expression vector. Overexpressing YC3.6 in E. coli will allow us to purify significant amounts of YC3.6 to be used in the study of the pH and oxygen sensitivity of the protein.

Contact Dr. Ettinger
Get more information about the Ettinger Lab

Research in the Lefcort Lab

Dr. Lefcort is currently on sabbatical leave.

Contact Dr. Lefcort
Get more information about the Lefcort Lab

Research in the Haydock Lab

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).

Positions available in spring 2010:

Project 1:
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.

Project 2:
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.

Contact Dr. Haydock
Get more information on the Haydock Lab

Research in the Poxleitner Lab

Positions available in spring 2010:

I am investigating the evolution of cocaine biosynthesis. Several species of the plant Erythroxylum produce cocaine, a tropane alkaloid, in their leaves. Two species, E. coca and E. novogranatense, are cultivated for the illicit extraction and processing of cocaine to be sold as an illegal drug on the international market. Despite its economic importance, the evolutionary history of the genus remains largely unknown, even for the cultivated species.  My research project will look for he presence or absence of alkaloid precursors in wild Erythroxylum species collected in the Caribbean and Cuba.  I am looking for a student to extract alkaloids from Erythroxylum leaf samples and identify individual alkaloids using gas chromatography. There will also be a DNA cloning and sequencing aspect to the project this year that will allow us to assay diversity within and between species. This data will help me answer the following questions: Where does synthesis of cocaine begin along the evolutionary tree versus synthesis of its precursors? Is synthesis of cocaine restricted to one evolutionary branch of the genus? Does synthesis of the precursors occur across the genus, is it restricted to one or two evolutionary branches, or does it occur across the family?  Over time, these questions could be expanded to investigate what is occurring at the gene level and how that relates to the same or similar genes in angiosperms.

Contact Dr. Poxleitner

Research in the Prusch Lab

Positions available in spring 2010:

Endocytosis is a fundamental process observed in most eukaryotic cells. Cells utilized surface membrane infolding and invagination or vesicle formation to internalize external solutes and particulate material. Protists including amoeboid and ciliated cells have been used as model cells systems to investigate the cellular mechanisms underlying these processes. Paramecium is a large ciliated protozoan that utilizes phagocytosis as a feeding mechanism to take up food material. Research in this lab will focus on first looking at the process of phagocytosis in these cells under control conditions and then experimentally manipulating the system to gain some insight to as to the signaling mechanism that triggers the process.

Contact Dr. Prusch

Research in the Shea Lab

My research interests lie in two areas of Parasitology. First, I am interested in parasite-altered behavior of hosts. Parasites that require multiple hosts often employ strategies to increase the probability of transmission to their next host, including altering host behavior. I will conduct lab experiments to study such questions in the trematode-snail system. Second, I am interested in using parasites as indicators of ecosystem health. Some parasites such as trematodes have complicated life cycles involving multiple hosts. Thus, the presence of the parasite in an ecosystem suggests the presence of its hosts. Since larval trematodes are easily and quickly collected from their snail intermediate hosts this research holds promise for a cheap and accurate way to assess ecosystems.

Contact Dr. Shea, S.J.
Get more information on the Shea Lab

Research in the Staub Lab

How do plethodontid salamanders communicate? They don't vocalize and generally don't use visual cues. They use pheromones, but little is known about the skin glands that produce these chemical messages, except for the well-studied mental gland of males that produce pheromones during the breeding season. While pheromones from the mental gland have been well studied, little is know about the pheromones that females produce or about the pheromones males produce from non-mental glands sources. We use published amino acid sequence data from the three known plethodontid pheromones (PRF, PMF, SPF) to design pheromone specific mRNA probes. Using in situ hybridization we can then detect which glands, of the many in salamander skin, are actually producing pheromone mRNA in both males and females. My lab is pursuing work on the following questions:
1) Where are courtship pheromones produced in males that lack specialized courtship glands?
2) Which glands in the post-cloacal region produce pheromones?
Projects involve learning histological techniques (dissecting tissue, embedding it in paraffin, sectioning and mounting tissue on microscope slides, staining), learning in situ hybridization to localize pheromone mRNA, analyzing and interpreting results, searching for and reading primary literature, and preparing a written report/poster.
My lab focuses on plethodontid salamanders (the genera Aneides, Ensatina, and Plethodon primarily), specifically focusing on understanding the variation in types of skin glands of various body regions, and the variation in gland type and size between sexes and species.  In general, my lab focuses on questions concerning the evolution of sexual dimorphism and sexual monomorphism.

Positions available in spring 2010:

It has been reported in the literature that the salamander species Taricha granulosa has submandibular courtship glands, yet there are no published histological descriptions of such glands. During the summer of 2009, males were examined for submandibular glands. Preliminary data suggest that T. granulosa does have sexually dimorphic chin glands. The PAS-positive, granular gland morphology was found only in male specimens and only in high concentrations on the anterior end of sagittal tissue sections. To confirm the presence of a sexually dimorphic courtship gland, non-reproductive males and a larger sample of reproductive females need to be examined. Planned research projects for two HHMI URAs are 1) examining female and non-reproductive male skin samples using histological techniques; and 2) using immunocytochemistry with a probe for pheromone mRNA to identify pheromone-producing glandular cells in reproductive males.

Contact Dr. Staub
Get more information on the Staub Lab

Research in the Swanson Lab

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.

Positions available in spring 2010:

Project 1:
Comparative biomaterial analysis of fiddler crabs. This student will conduct nanomaterials testing of fiddler crab shells recently collected in the field. The student will become familiar with several testing techniques including toughness testing, bulk materials testing, nanoindentation and microindentation. These data will be compiled for 20 species and analyzed in conjunction with already-collected morphological data.

Project 2:
Manuscript writing for a comparative study of fiddler crabs. This student will analyze data that was collected this summer using several statistics packages, produce publication-quality figures presenting these data, write and revise a manuscript for submission this semester.

Contact Dr. Swanson
Get more information on the Swanson Lab

Research In Chemistry and Biochemistry

Research in the Cremeens Lab

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.

Positions available in spring 2010:

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.

Contact Dr. Cremeens
Get more information on the Cremeens Lab

Research in the Cronk Lab

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.

Contact Dr. Cronk
Get more information on the Cronk Lab

Research in the Ross Lab

I am interested in the development of porous nanomaterials for bioanalytical applications. In particular, we'll investigate the use of crystallized assemblies of nanospheres (artificial opals) for chemical sensing and separation challenges. A key research thrust this summer will be the study of entrapped lipid bilayers within artificial opals. Lipid bilayers on solid surfaces are biological membrane mimics that have been invaluable for biophysical studies of membrane proteins and lipids but are considered insufficiently robust for non-academic use (the lipid bilayer is structurally similar to a soap bubble). Preliminary results indicate that artificial opals can serve as a protective scaffold for embedded lipid bilayers conferring several remarkable measures of stability and a dramatic increase in membrane surface area. With the goal of extending the operational utility of lipid bilayers, we will investigate the influence of the opal scaffold on membrane properties such as lipid phase and order. Material development studies will seek to maximize the structural resemblance of opal supported lipid bilayers to established membrane mimics. Concurrently, these materials will be investigated as stationary phases for high throughput membrane affinity studies, which is just one example of a potential application for lipid bilayers enabled by the opal support.
If you are interested in discussing research opportunities in my laboratory, please feel free to drop by my office and talk. All student researchers will be introduced to inorganic colloidal synthesis, self-assembly of nano- and bio-materials, surface chemistry, fluorescence microscopy, adsorption assays, and the application of a range of spectroscopic techniques to novel materials.

Position available in spring 2010:

A research opportunity is available for a student in the areas of analytical and colloid & surface chemistry in Dr. Ross’s laboratory. Methodology for rapid assembly of lipid bilayers on sub-micron silica colloids was recently developed in our laboratory. The next step in this project is the application of the materials to the study of bilayer partition events using a liquid chromatography (LC) format. The goal for this semester is the chromatographic resolution of model lipophilic compounds on lipid-modified silica stationary phases. Over the HHMI award period, the student will be expected to become proficient in methodology and componentry of a capillary-LC system that utilizes fluorescence microscope detection. Students with better-than-average manual dexterity and little fear of the dark are especially encouraged to apply.

Contact Dr. Ross
Get more information on the Ross Lab

Research in the Shepherd Lab

Rhodoquinone (RQ) is an essential cofactor 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), an important lipid component involved in the aerobic respiratory chain. Both RQ and Q have a fully substituted benzoquinone ring and a polyisoprenoid side chain of varying length (depending on species). The only difference between the structures is that RQ has an amino group (NH₂) instead of a methoxy group (OCH₃) on the quinone ring.  Therefore, the biosynthetic pathways of RQ and Q are proposed to be similar and may diverge from a common precursor. The biosynthesis of Q has been well-characterized in both eukaryotic and prokaryotic species.  It has recently been shown in Dr. Shepherd’s laboratory that RQ and Q are derived from demethylubiquinone (DeMeQ) 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. The main focus of Dr. Shepherd’s current research is to identify the candidate gene(s) and polypeptide(s) responsible for amino-transfer in RQ biosynthesis using the model organisms, R. rubrum and C. elegans. Selective inhibition of the amination step in RQ biosynthesis may lead to highly specific antihelminthic drugs that do not have a toxic effect on the host.

Position available in spring 2010:

I received a small grant last spring from the College Donors Fund at Gonzaga for whole-genome sequencing of the F11 and RF110 strains of R. rubrum. Upon initial sequence analysis this summer, we identified a mutation in F11 (a stop codon) in a putative methyltransferase gene involved in RQ biosynthesis that had been repaired in the revertant, RF110. In fact, this was the only significant nucleotide difference between the two strains. Using the Predictprotein program, a secondary structure of the putative methyltransferase was predicted. The predicted structure fits well with the seven beta strand family, although one of the beta strands is missing from the C-terminus. The four predicted motifs are shown in Fig. 1.

FIG.1. Predicted secondary structure of ATCC 11170 YP_428309.  Data was obtained from predictprotein.org and shows four motifs characteristic of the seven beta strand family of methyltransferases.

Our immediate goal this fall will be to perform a complementation experiment with the F11 mutant, using the proposed methyltransferase gene from wild-type R. rubrum (ATCC11170). The gene will be cloned using the broad-host-range plasmid pRK404 (from E. coli that has resistance to tetracycline (Tc^r). pRK404 contains five functional single cut sites and these are for the EcoR1, SalI, AccI, BamHI, and HindII PstI restriction enzymes.¹ The R. rubrum chromosomal DNA sequence will be amplified and inserted into the pRK404 vector and ultra competent E. coli (JM109) will be transformed with the plasmid. To transform the F11 mutant, tri-parental mating must performed between JM109 and the F11 using the helper plasmid, pRK2013 (from E. coli UQ377), which has kanamycin resistance (Km^r).² Direct transformation of R. rubrum provides very poor yields and the tri-parental mating system has been optimized by Dr. Gary Roberts at the University of Wisconsin, Madison, and detailed protocols and plasmids have already been obtained from his group.³ It is hypothesized that a gene that can rescue F11 is likely to be involved in RQ biosynthesis, because RF110 regains the ability to synthesize RQ. If the gene is validated through the complementation experiments, we plan to express the protein and ultimately perform in vitro assays with our farnesylated substrates for further characterization.

1. Ditta, G.; Schmidhauser, T.; Yakobson, E.; Lu, P.; Liang, X. W.; Finlay, D. R.; Guiney, D.; Helinski, D. R. Plasmid 1985, 13, 149-153.
2.  Ely, B.  Mol. General Genet. MGG 1985, 200, 302-304.
3.  Zhang, Y.; Pohlmann, E. L.; Ludden, P. W.; Roberts, G. P.  J. Bacteriol. 2000, 182, 983–992.

Contact Dr. Shepherd
Get more information on the Shepherd Lab

Research in the Vannelli Lab

Project 1:  Synthesis of macrocyclic compounds for use in photodynamic therapy of cancer
The goal of this project is to synthesize and characterize macrocyclic molecules that will serve as components of a small library of compounds with potential as sensitizers for photodynamic therapy (PDT). Photodynamic therapy is the non-invasive treatment of diseases or infections using light, molecular oxygen, and a photosensitizer. The role of the photosensitizer is to absorb the incoming light and transfer this energy to molecular oxygen. The energetically excited oxygen molecule then causes extensive local oxidative damage. PDT has been approved for the treatment of some cancers, as well as, a condition known as macular degeneration (a leading cause of blindness among the elderly). Furthermore, PDT has demonstrated potential in the treatment of bacterial infections. Students working on this project will execute the multi-step total synthesis of a target macrocycle. Each intermediate in the synthesis will be fully characterized by NMR spectroscopy, mass spectrometry, and UV-visible spectroscopy (where applicable). Once, the macrocycle is synthesized in adequate quantities, we will chemically link it to a targeting molecule specific for prostate-cancer and, in collaboration with Prof. Berkman’s research group at WSU, we will study the cellular uptake of this photosensitizer in cultured cancer cells.

Project 2:  Expression, purification and characterization of the Arsenite Oxidase complex from the hyperthermophile Thermus thermophilus
Students working on this project will be part of an effort to recombinantly express, purify, and characterize the large and small subunits of the Arsenite Oxidase complex the archeon Thermus thermophilus. Arsenic is a toxic and carcinogenic heavy metal that poses an increasing threat to global health. Arsenic enters the drinking water supply through either the biogenic release of adsorbed arsenic or industrial pollution (i.e. mining, pesticide use, electronics manufacturing, and glass manufacturing). Interestingly, there are organisms that have evolved metabolic pathways that either eat (arsenite as initial electron source) or breathe arsenic (arsenate as terminal electron acceptor). We hope to exploit the selectivity of the isolated Arsenite Oxidase complex to investigate applications in the selective biosensing of arsenite in drinking water and biofluids. Students involved in this project will have the opportunity to clone, express, and purify the two subunits of the target Arsenite Oxidase complex. Once pure protein is isolated, the recombinant protein products will be characterized using such techniques as mass spectrometry, gel filtration chromatography, spectroscopic activity assays, X-ray crystallography, and HPLC.

One position available in Spring 2010:

The selected HHMI funded undergraduate researcher will be involved in research pertaining to the second project listed above.

Contact Dr. Vannelli

Research in the Warren Lab

The world, especially the industrialized world, is facing 2 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.

Position available in spring 2010:

I am looking for a motivated independent student to evaluate lactate analogs for their lactate dehydrogenase activity.

Contact Dr. Warren

Research in the Watson Lab

In the Watson lab, we study the structure and function of the enzyme HMG-CoA reductase (HMGR). In humans, this enzyme is the key regulatory point for the biosynthesis of cholesterol and is the target for statin drugs.  Bacteria also use this enzyme, and it has been shown by other labs that it's a vital enzyme for the survival of certain pathogenic bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). The bacterial forms of HMGR are considered to be good candidates for novel antibiotics against these organisms.
Recently, we have discovered that the proposed mechanism for this enzyme may not be accurate. There are many projects in the lab currently, all aimed toward a greater understanding of how this unusual enzyme works:
1) Synthesis of substrate analogs to probe one of the key substrate binding sites as a precursor to the development of novel inhibitors
2) Cloning, expression and purification of a new bacterial HMGR from an organism that causes fatal infections in the lungs of end-stage cystic fibrosis patients
3) Structural characterization of a domain found only in bacterial HMGRs that transitions from unstructured to structured over the course of the reaction.
Students in the Watson lab will learn key basic biochemical techniques such as protein production, purification and characterization, as well as gain experience in molecular biology techniques such as site-directed mutagenesis and biophysical methods such as UV-vis and fluorescence spectroscopy

Position available in spring 2010:

I am seeking one student who will begin a project to characterize the structure of an important domain in bacterial HMG-CoA reductases (HMGR), an enzyme known to be vital for the survival of a number of pathogenic bacteria and thus is a potential target for new antibiotics. This student would be involved in determining how HMGR is affected by treatment with pepsin, an enzyme that cleaves proteins into shorter pieces. The student will then characterize the products of this reaction by mass spectrometry. This set of experiments is vital to a larger study in which important dynamic properties of HMGR structure and function will be studied by hydrogen-deuterium exchange rates using mass spectrometry, in collaboration with a laboratory at Oregon State University.  The student will have the opportunity to learn common biochemistry laboratory techniques involved in protein purification, including working with bacterial cultures, chromatography and protein gel electrophoresis.

Contact Dr. Watson

Research at WWAMI

Research in the Roberts Lab

Research in my lab focuses on the role of the epididymis in sperm maturation and function. Sperm are produced in the testis but gain the ability to fertilize an egg as they transit the epididymis. As sperm transit the epididymis they acquire proteins necessary for normal function from the epididymal fluid, which is a secretory product of the epididymal epithelium. The purpose of our research is to understand this maturation process.Our current main focus in on the role of CRISP1, an epididymal protein acquired by the sperm, in the regulation of sperm functions such as the acrosome reaction. Likewise, the role of CRISP4, a second CRISP protein produced in the epididymis and related to Crisp-1, is also under investigation. Experiments are also being performed to determine how the two isoforms of the CRISP1 protein (Proteins D and E) become attached to the sperm plasma membrane. This work has implications for clinical conditions of sperm dysfunction leading to male infertility.
My lab is also interested in the protein composition of sperm and the origin of sperm proteins. In collaboration with colleagues at Pacific Northwest National Lab, we have undertaken a total proteomic analysis of human sperm to determine the proteins required for sperm maturation. We are also using signal-trap cloning to identify and catalog cDNAs from the mouse epididymal epithelium encoding secretory proteins that become part of the sperm proteome.

Contact Dr. Roberts

Research in the Chai Lab

For information on research in the Chai lab, please visit her homepage at WSU.

Contact Dr. Chai

Research in the Kapás Lab

We are interested in understanding the relationship between the regulation of sleep and metabolism. We study the role of metabolism- and feeding-related humoral and neuronal signals in the regulation of biological clocks, sleep-wake activity and arousal. Also, we investigate the effects of clocks and sleep, and the impairments thereof, on metabolism, eating and thermoregulation. We use integrative approach, in vivo rodent models, with simultaneous measurements of the amount and intensity of sleep, oxygen uptake, carbon dioxide production, food intake, body temperature, locomotor and wheel running activities supplemented by blood sampling for hormone measurements.

Contact Dr. Kapás

Research in the Szentirmai Lab

The focus of my research is how sleep, metabolism and body temperature regulation are related. In the laboratory, we work with laboratory animals, with rats and mice. A student who is interested in this type of research can participate at many levels, from doing surgeries on animals through data collection, to data analysis.

Contact Dr. Szentirmai

Research in the Wisor Lab

Contact Dr. Wisor