• About the Department
• Undergraduate Study
• Graduate Study
• People
• Research
• Awards and Scholarships
• Giving
• Careers
• Job Openings
• FAQ
• Links

Seminar Schedule

Spring 2012

Please join us for our regular seminar series in Burruss room 238 on Fridays at 12:20pm-1:10pm

Date	Speaker/Title
January 13	n/a
January 20	Steve Cresawn, JMU Title: "A Genomic Perspective of Bacteriophages Through the Development of Computational Tools".  Abstract
January 27	Tim Bloss, JMU Title: "What doesn’t kill you…: cell-stress response in C. elegans and its implications for disease development and treatment".  Abstract
February 3	Heather Griscom, JMU Title: "Return of the Giant:  Experimental Seedling Trials with American Chestnut" Abstract
February 10	Marta Bechtel, JMU Title: “Form Makes Function” – The Road to a Tissue-Engineered Cornea.  Abstract
February 17	Andy Johnson, Univ. Penn. Title: "Metabolic regulation during the immune response" Abstract Watch a video of the talk
February 24	Kimberly Terrell, National Zoo Title: "Investigating the Influence of Projected Climate Change on Hellbender Physiology".  Abstract Watch a video of the talk
March 2	Justin Brown, JMU Title: "Role of Brain Stem Serotonin in the Cardiovascular Response To Stress In Rats - Applications to Sudden Infant Death Syndrome (SIDS)" Abstract
spring break
March 16	Butch Brodie, UVa Title: "Predator-prey arms races between snakes and newts from molecules to landscapes". Abstract
March 23	Graduate student presentations: Molly Bletz: "Transmission and persistence of probiotic skin microbes on red-spotted newts" Abstract Andy Loudon: "Cutaneous microbial community dynamics of amphibians" Abstract
March 30	Clint Epps, OSU Title: "Contrasting connectivity across species and time scales for large mammals in East Africa" Abstract
April 6	Graduate student presentations: Caylin Murray  Matthew Eddy Marcus Skaflen Caylin Murray: "The effect of cellular stress on the unfolded protein response in C. elegans" Matthew Eddy: "The effect of Dengue Virus E protein on chondrocyte immune response" Marcus Skaflen: "Determining the Role of a Conserved Hypothetical Protein in the Erythrocytic Life Cycle of Plasmodium falciparum" Abstracts
April 13	Biosymposium Keynote speaker: Tom Buckley, Biology Department, Sonoma State University.  Title:"The poetry of nature is written in calculus: Why biologists need intensive immersion in applied mathematics and computation."
April 20	Graduate student presentations: Jade Irby: "Synthesis, Antibacterial Activity, & Structure-Function Analysis of  a Novel Series of Multi-Headed Amphiphiles" Marc Carpenter: "Soil as a source of the fecal indicator, Enterococci, in a coastal watershed. " Abstracts
April 27	Mark Hudy, National Aquatic Ecologist – East USDA Forest Service; Adjunct, JMU Biology department. Title: 'Status and Trends of Brooktrout at Various Scales of Analysis'

Steve Cresawn: Abstract

Bacteriophages (viruses that infect bacteria) are the largest known reservoir of novel genetic sequences on planet Earth.  These viruses are critical for carbon cycling in the environment, useful as diagnostics in the laboratory, and are being explored as anti-bacterial agents in the clinic.

Bacteriophage genomes have mosaic architectures and are replete with small open reading frames of unknown function, presenting challenges in their annotation, comparative analysis, and representation.  We are developing a new bioinformatic tool, Phamerator, that assorts protein-coding phage genes into phamilies of related sequences using pairwise comparisons to generate a database of gene relationships. This database is used to generate genome maps of multiple phages that incorporate nucleotide and amino acid sequence relationships, as well as genes containing conserved domains. Phamerator also generates phamily circle representations of gene phamilies, facilitating analysis of the different evolutionary histories of individual genes that migrate through phage populations by horizontal genetic exchange.  Phamerator represents a useful tool for comparative genomic analysis and comparative representations of bacteriophage genomes.  The analysis of these genomes is an important component of a number of courses in our department (Viral Discovery, Viral Genomics, Bioinformatics, and Genomics).  The contributions of these students will be highlighted.

 

Tim Bloss: Abstract

Maintaining cell viability and function is a complex and dynamic process, particularly in the face of the significant and persistent stresses that all cells face throughout their existence. Cell stress can take many forms, all of which trigger responses ranging from complete resolution of the stress to cell death. Poorly regulated stress responses are closely linked to a multitude of diseases, including neurodegeneration and cancer, therefore our understanding of cell-stress management is essential to our understanding of these disease pathologies. We study cell-stress response in the model organism C. elegans., in particular, the management of stress associated with misfolded proteins.  Through the use of RNA interference and GFP-fusion protein expression, we are able to induce misfolded protein stress in C. elegans and evaluate the subsequent response. Our results are providing insights into how specific cell types handle misfolded protein stress and how these responses differ from cell-type to cell-type, resulting in rescue or death. The accumulation of misfolded proteins is a hallmark of many neurodegenerative diseases, including Huntington’s and Alzheimer’s; we hope our understanding of how C. elegans handles this stress will provide insights into the function of homologous stress-response systems in human cells, and how they work, or don’t work, in the face of these diseases.

 

Heather Griscom: Abstract

American chestnut was once a dominant canopy species in many eastern deciduous forests.  Unfortunately, this ecologically and economically important species has been eliminated from the forest canopy for over sixty years due to an introduced fungal pathogen. We are almost at the point of introducing blight-resistant chestnut hybrids into our forests.   However, little is known about American chestnut’s ecological niche or whether hybrids have retained American chestnut ecophysiological characteristics and growth.  We have been experimenting with two levels of light and soil in parallel field and greenhouse studies for the past four years.  Thus far, we have found that optimal sites for planting American chestnut hybrids are in small gaps located within upper slope, ridge sites. Seedlings performed relatively well, had good survival rates, and were the most competitive with tulip poplar, their major competitor, under these conditions.  In addition, we did not detect a significant difference between American chestnut and the hybrids for any performance parameters measured.

 

Marta Bechtel: Abstract

 

Corneal disease is the second-leading cause of blindness in humans worldwide and the only current treatment is corneal tissue transplantation.  This results in high demand for cornea tissue, which currently exceeds supply, making a tissue engineered cornea highly desirable.  One approach to tissue-engineering a cornea is based upon the concept that various components of a tissue act in concert to provide the specific functions of a tissue.  This tissue-engineering approach includes selecting the appropriate cell type(s), appropriate scaffold material, and the appropriate signals (such as growth factors, mechanical stimuli, flow conditions, etc.), which all contribute to formation of the three-dimensional (3D) architecture of a functional tissue.  An important feature of cornea tissue is the need to be transparent, so an in vitro engineered cornea must also be transparent to be useful.  Research in my lab is currently focused on understanding and controlling the cell phenotype of corneal keratocytes, the cell type found in the stromal layer of cornea tissue, and the cell type that plays an important role in maintaining cornea transparency.  We employ a rabbit cornea tissue model to study how various artificial scaffolds, and biochemical signaling molecules can influence the functional differentiation of corneal keratocytes as these cells move through a wound healing phenotype toward a fully differentiated phenotype that yields a transparent tissue.  In addition to studying cornea tissue engineering, we hope this work, in conjunction with our collaborators, will contribute to a better understanding of corneal wound-healing mechanisms associated with corneal haze problems resulting from eye surgeries, and provide a model system for studying new ophthalmic drugs.

 

Andy Johnson: Abstract

 

The immune system attempts to eliminate cancerous cells and invading pathogens, but evasion tactics by these diseases can result in persistent tumors or infections. The continued presence of diseased cells in these contexts leads to an over-stimulated, dysfunctional immune state termed exhaustion. Exhausted immune cells have an impaired ability to fight infections compared to the cells generated following vaccination. These differences are at least partially caused by inhibitory receptors on the exhausted cells that are believed to send negative signals that block immune activation. Exhausted cells also display altered energy metabolism just as exhausted humans do during prolonged exercise such as a triathlon. Metabolic processes can regulate the development and function of many cell types including those of the immune system. These characteristics of exhausted immune cells may be linked as inhibitory receptors were recently shown to block pathways that control metabolic processes. Importantly, though originally observed in a mouse model of chronic infection, clinical researchers also found that blocking inhibitory receptors partially reverses immune exhaustion, enhancing the immune system’s ability to fight cancers including AML.

 

My goal is to understand how inhibitory receptors and metabolic pathways regulate immune cell function in order to find ways to reverse immune exhaustion and help the body’s natural defenses eliminate cancer and chronic infections. To address this, I have begun analyzing the metabolic pathways active in exhausted cells that express different combinations of inhibitory receptors. I have exciting preliminary results showing that particular subsets of exhausted cells have decreased and delayed activation of a central regulator of metabolism. I now plan to monitor this metabolic pathway following blockade of inhibitory receptor activity and to enhance this metabolic pathway using clinically proven pharmaceutical drugs. Ultimately, this will lead to a more complete reversal of immune exhaustion by directly targeting the dysfunctional metabolic processes that are required by the immune system to destroy cancerous or infected cells.

 

Kimberly Terrell: Abstract

 

The Appalachian region is home to half of the United States' salamander species, including the hellbender (Cryptobranchus alleganiensis), but populations throughout this area are mysteriously vanishing.  Climate change is globally linked to enigmatic amphibian declines and will likely impact Appalachian salamanders and other ectothermic species adapted to cool microclimates.  This talk will focus on an ongoing study at the Smithsonian Conservation Biology Institute (Washington, DC) that examines the influence of changing temperature on hellbender immune function and metabolism.  Working collaboratively with state, federal, academic and NGO partners, we are using both lab and field-based approaches to determine if climate change can act synergistically with other stressors (e.g., water quality) to threaten salamander survival.  These studies will establish certain physiological limits of (or opportunities for) climate change adaptation in hellbenders and may provide insight into the enigmatic declines of Appalachian amphibians.

 

Abstract: Justin Brown

 

 

Dysfunction in serotonin (5HT) neurotransmission in the brainstem of infants may disrupt protective responses to stress and increase the risk for Sudden Infant Death Syndrome (SIDS). The raphé pallidus (NRP) and

 other brainstem nuclei are rich in 5HT and are thought to mediate stress responses, including increases in blood pressure (BP) and heart rate (HR). Determining how 5HT neurotransmission in the brainstem mediates responses to stress will help to explain how dysfunction in neurotransmission could increase the risk of SIDS. It was hypothesized that alterations in neurotransmission in the NRP, specifically activation of the 5HT-1A receptor subtype, would block cardiovascular responses to various types of exogenous stress. Using aseptic techniques, male Sprague-Dawley rats were instrumented with radiotelemetry probes which enabled non-invasive measurement of BP and HR. An indwelling microinjection cannula was also stereotaxically implanted into the NRP for injection of drugs that altered local 5HT neurotransmission. Following a one week recovery period, rats were microinjected with either muscimol (GABA-A receptor agonist), 8-OH-DPAT (agonist to the inhibitory 5HT1A receptor), or a vehicle control (artificial cerebral spinal fluid; ACSF) immediately prior to exposure to one of three stressors: handling, air jet, or restraint. Physical handling and restraint of the animal were designed to elicit a mild and a maximal stress response respectively; while an air jet directed at the rat’s face was used to provoke a psychological stress that did not require physical contact. All three stressors elicited similar and significant elevations in HR and BP following ACSF that persisted for at least 15 min with BP and HR elevated by ∼14.0 mmHg and ∼56.3 bpm respectively. The similarity in the stress responses suggest even mild handling of a rat elicits a maximal sympathoexcitatory response. The stress response was abolished following 8-OH-DPAT or muscimol microinjection suggesting the cardiovascular responses to stress are mediated by the NRP and likely involve the 5HT-1A receptor. Impairment in 5HT1A receptor function in the NRP likely impairs the normal cardioprotective responses to stress and may contribute to the etiology of SIDS.

 

Abstract: Butch Brodie

 

Arms races between predators and dangerous prey can lead to rapid and elaborate counter-adaptation. Newts of the genusTarichapossess the sodium channel blocker tetrodotoxin, which is lethal to most predators. Garter snakes have repeatedly evolved resistance to TTX through their ecological interaction with toxic newts. Sodium channel genes are highly conserved across vertebrates, yet garter snakes have evolved resistance through a few key mutations in these proteins in a very short evolutionary time. Snake species around the world have evolved TTX resistance through the same set of mutations, painting a clear picture of constraint driven convergent evolution at the protein level. Understanding the molecular mechanism of adaptation helps explain the dynamics of predator-prey arms races in this system, wherein predators some times "win" the race, but prey never do.

 

Abstract: Molly Bletz

The infectious disease, chytridiomycosis, is considered one of the leading causes of these enigmatic amphibian declines in pristine areas. Caused by the cutaneous fungal pathogen Batrachochytrium dendrobatidis (Bd), chytridiomycosis is decreasing amphibian biodiversity, driving >200 species to extinction across many continents. Cutaneous mutualistic bacteria are a critical part of an amphibian’s defense against Bd infection. The use of these beneficial bacteria as probiotics for susceptible species is likely the most feasible conservation strategy.

  It is well documented that amphibians maintain populations of microbiota on their skin; however, how these particular beneficial species are acquired, maintained and transmitted is not fully known. Therefore, the aim of the proposed research is to investigate the transmission and maintenance of beneficial bacteria on amphibians and the necessity of environmental bacterial reservoirs for probiotic conservation methods to allow continued resistance to Bd. Using outdoor artificial ponds housing red-spotted newts, I plan to manipulate two factors, presence and absence of a probiotic bath and presence and absence of a probiotic environmental reservoir.

Over seven weeks, I will test how these factors influence newt susceptibility to Bd infection. Investigating maintenance and transmission can determine whether amphibians are dependent on environmental microbial populations for maintaining these cutaneous bacteria or if the microbial community is self-sustaining once acquired. Transmission and maintenance also have strong implications for probiotic conservation strategies and can provide vital insight in developing effective conservation strategies to help susceptible species.

 

Abstract: Andy Loudon

Emerging infectious diseases are a major threat to biodiversity. The fungal disease chytridiomycosis has been documented causing amphibian extinctions and declines globally. Indeed, the disease is considered the largest disease threat to biodiversity. One defense possessed by amphibians to combat chytridiomycosis is a cutaneous bacterial community. A number of cutaneous bacterial species have been determined to inhibit Batrachochytrium dendrobatidis (Bd), the causal agent of chytridiomycosis; however, their relative abundance within their community is unknown.  The stability of amphibian bacterial communities is also unexplored. Stability is defined as resistance to a disturbance; resilience is defined as recovery from a disturbance and constancy is defined as temporal stability. Using 454 pyrosequencing, I propose to investigate the structure and stability of cutaneous bacterial communities of the red-backed salamander (Plethodon cinereus) in regards to several major perturbations: moving individuals from the field to the laboratory, housing individuals with and without an environmental reservoir, and infection with B. dendrobatidis. As another objective, I will determine how the abundance of culturable species compares to that of total bacteria present in the community since most bacterial species are not easily cultured. This objective will establish if the stability of a cultured community is an adequate indicator of total community stability.  I also propose to investigate temporal constancy to determine if temperature variations that mimic climate change projections influence bacterial communities’ structure and function of the eastern hellbender (Cryptobranchus alleganiensis alleganiensis).

Abstract: Clint epps

Connectivity is often touted as a solution to help maintain biodiversity in
reserves and prevent rapid loss of genetic diversity. However, dispersal abilities vary widely across species and the effect of landscape on movement and gene flow is unknown for most species. Thus, the basis for attempting connectivity conservation among specific reserves is often unclear. East African reserves are often cited as a classic example of protected areas isolated in a sea of human activity, but little is known about the potential for connectivity among reserves. Our research group has used both field surveys of animal occurrence and population genetic data to describe and contrast patterns of connectivity for large mammals in Tanzania. In this seminar, I will present comparative estimates of long-term gene flow for four species of large herbivorous mammals, as well as analysis of changes in connectivity for African elephants from historical through present-day timeframes. Our findings will help frame the discussion regarding connectivity and the allocation of conservation resources.

 

 

Abstract: Caylin Murray

Cells are constantly dealing with stresses that threaten to disrupt the homoeostasis required for survival. Certain stresses can result in accumulations of misfolded protein in the endoplasmic reticulum (ER), an organelle central to the maintenance of cell viability. Responsibilities of the ER include: post-translational modification of folded proteins, chaperone-guided folding of nascent polypeptide chains, and the synthesis of lipids and steroids. When proper protein folding is inhibited in the ER, highly conserved mechanisms are engaged to minimize the physiological stress on the organelle.  One such mechanism is the unfolded protein response (UPR). The UPR can be broken down into three responses: First, the UPR works to restore homeostasis by decreasing translation of proteins; next, there is an increase in the production of molecular chaperones that bind directly to proteins to prevent their misfolding; finally, the UPR degrades improperly folded proteins that have accumulated within the ER.  Even with these controls in place, the environment in the ER may become too toxic for cell viability. In these cases, the UPR shifts focus to death and disposal of the cell by apoptosis or autophagy.  The goal of this study is to explicate the balance between autophagy and apoptosis in response to the UPR through manipulation of the C. elegans protein Inhibitor of Cell Death-1 (ICD-1). Loss of ICD-1 appears to induce an accumulation of misfolded protein in the ER, resulting in the induction of the UPR. We will characterize the scope of the UPR in C. elegans lacking ICD-1 by removing ICD-1 from worms deficient in specific aspects of the UPR. Ultimately, we hope to learn how the UPR is controlled  and extrapolate these finding to the human system, which contains highly conserved UPR mechanisms relative to C. elegans.

 

Abstract: Matthew Eddy

Dengue Fever and, the more severe, Dengue Hemorrhagic Fever has been a problem for people living in tropical regions with elevated endemic mosquito populations.  50-100 million people are currently thought to be infected by this pathogen every year. The disease causes a number of symptoms ranging from rash, a mid-grade fever and arthralgia (joint pain), to hemorrhaging of internal organs and death in extreme cases. My research focuses on arthralgia and its association with cells known as chondrocytes, the cell population present in cartilage tissue, as well as characterizing potential receptors of the Dengue virus in macrophages. To facilitate these studies, I will be using an envelope protein of the Dengue virus to stimulate an immune response in both cell types and checking gene expression patterns over a time course using quantitative Real-Time PCR. Once genes have been identified in response to envelope protein, I will be running protein expression analysis using ELISA or immunofluorescence microscopy. In our macrophage studies we will be selectively blocking receptors known to facilitate viral uptake using antibodies and blocking ligands. Gene expression analysis and protein changes will be monitored in macrophages following incubation with viral envelope protein as well. These studies hope to elucidate the immune response generated by chondrocytes exposed to the viral envelope protein, and determine the effects of receptor blocking in macrophages to gain a better understanding of dengue pathogenesis.

 

Abstract: Marcus Skaflen

Malaria is a disease that causes 300-500 million cases annually, approximately 1 million of these cases resulting in death. Malaria is an infection caused by the parasitic protozoan Plasmodium. There are 5 species that can infect humans, Plasmodium falciparum causing the majority of the fatalities. The genome for Plasmodium falciparum was sequenced in 2005 and 60% of the genome encodes for unknown proteins. The last five years have lead to the development of several genetic tools for manipulating the genome, and I will be studying a mutant strain of Plasmodium falciparum. A forward genetic screen created a mutant phenotype that severely attenuated the growth in the blood stages. I will be investigating the function of the protein that the mutation disrupted using bioinformatics, examining localization and expression, and investigating protein to protein interactions. I will also be investigating the phenotype of the mutant strain, examining the erythrocytic life cycle in culture.

 

Abstract: Jade Irby

In the US, approximately two million patients a year acquire a hospital-acquired infection during their stay, leading to almost 100,000 deaths. An increasing number of these infections are caused by multi-drug resistant organisms. Development of novel, potent antimicrobial compounds could be used in eliminating or reducing potential pathogens in the hospital setting. As a continuation of our previous research on bicephalic amphiphiles, which correlated antibacterial activity with head group arrangement and chain length, the antimicrobial activity of two novel series of amphiphiles was investigated. Amphiphiles of series “A” have a tri-substituted arene core. Attached to the arene core are three head groups, each with a hydrocarbon tail (from 8-16 carbons) of the same length linked to each head group. Amphiphiles of series “B” are a structural variation of “A” with one of the head groups a pyridine without a hydrocarbon tail. These series of amphiphiles were assayed for antimicrobial effectiveness against Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, and Escherichia coli by performing standardized minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. MIC and MBC values for these amphiphiles were in the low micromolar range. Specifically, the compound M-P,12,12, from series “B” (meta-pyridine, 12 carbon chain, 12 carbon chain) was most effective for all strains tested, with MIC and MBC values of 2mM for S. aureus, 2mM for E. faecalis, 4mM for E. coli, and 8mM for P. aeruginosa. In addition to being the most effective compound, the MIC values of M-P,12,12 were less than control compounds DTAB, CTAB, and Lysol. The MIC of M-P,12,12 for P. aeruginosa, a difficult to treat organism, was 4 fold less than the MIC of Lysol for P. aeruginosa (8mM and 32mM, respectively). Structure-function analysis has identified simple trends in the series of amphiphiles tested. Amphiphiles of series “A” were more effective against gram-positive bacteria. However, amphiphiles of series “B” were more effective than amphiphiles of series “A” against all strains tested.  Antimicrobial activity of amphiphiles of series “B” was found to be reliant on the hydrocarbon chain length of the substitutions, with higher MIC values when chain length was shorter or longer than 12 carbons with all strains tested. This research builds upon initial discoveries regarding structure and bioactivity to identify structures with the most potent antimicrobial activity while remaining safe. 

 

Abstract: Marc Carpenter

The Clean Water Act of 1972 initiated a raised awareness of the extent of the pollution in U.S. waters and the need for monitoring and identifying sources of contamination.  Surface water quality is routinely evaluated using fecal indicators, such as Enterococcus spp.  Recent studies in a south Texas watershed  showed that fecal bacteria were being transported to water via agricultural land runoff following rainfall, suggesting that soil, rather than fecal material, may be a source of these bacteria. In this study, soils from fields under different crop covers have been sampled to determine seasonal levels of enterococci and species of enterococci have been identified sing the BIOLOG™ Microbial Identification System.  A series of laboratory experiments will be conducted to evaluate the ability of enterococci to survive in soil, using a South Texas soil…name it. . Top soil samples will be placed in small columns and inoculated with environmental and ATCC strains of a species of Enterococcus, which has been isolated from both soil and water in the watershed.  Experiments will be set up at several temperatures (40o, 25o, 10oC) and moisture (dry or equivalent to 2.5 cm rainfall).  Enterococci will be enumerated at several time intervals using standard membrane filtration on selective media for Enterococcus spp. (mEI), following extraction from soil.  Field sampling showed higher numbers of enterococci in soil during cooler months and preliminary lab results indicate that survival of enterococci in soil is affected by temperature, with greater persistence at lower temperatures.  This data support the hypothesis that soil can act as a reservoir for fecal indicator bacteria in the environment.