Salmonella : environment signaling and genetic regulation of a Type III secretion system in an effort to cause infection
Salmonella is a continuing problem throughout the world, contributing to millions of infections every year. These infections are initiated when the bacteria are ingested and then penetrate the M cells of ileal Peyer's patches found within the small intestine. Proteins encoded by a cluster of genes on the chromosome known as Salmonella Pathogenicity Island 1 (SPI-1) play an integral role in the invasion process by injecting effector proteins via a type III secretion system directly into the host cells thereby forcing the uptake of the bacteria into the host cell . Salmonella invasion is tightly controlled by the bacterium and the genes necessary for invasion are activated by specific environmental signals such as low oxygen concentration and high osmolarity, condition that are believed to exist within the small intestine. The hilA gene found within SPI-1 is a transcriptional activator of the genes required for Salmonella invasion. When conditions are optimal for bacterial invasion, hilA is activated, which in turn leads to the expression of the genes necessary to build the type III secretion needle structure and the effector g enes. These effectors are then secreted through this apparatus into the targeted host cells thereby forcing the uptake of Salmonella
In an effort to understand how the different environmental signals regulate hilA expression, a new repressor of hilA, named hilE was identified. This gene is regulated by specific environmental signals and has been shown to repress hilA expression when conditions are not optimal for invasion. During the characterization of hilE, I was able to map hilE to the Salmonella genome. The region in which hilE was identified exhibits many of the hallmark characteristics that define pathogenicity islands including the clustering of Salmonella specific genes, a dramatic change in the %GC in the region, and the association of specific mobilizable elements. Salmonella virulence is dependent on the expression of these pathogenicity islands. Future work is being aimed at identifying these other Salmonella specific genes within what we are calling Salmonella pathogenicity island 6, and assessing what impact they have on Salmonella virulence.
Additional work involves collaborative efforts with the Bill Picking lab at the University of Kansas in which we are creating specific mutation in Salmonella and Shigella in effort to understand how the overall Type III secretion system functions. We are also working with the Brad Jones lab at the University of Iowa where we are screening Salmonella with a plasmid library of cyclic polypeptides. We are trying to identify protein products that repress the expression of the Salmonella regulatory genes and thereby inhibit the ability of the bacteria to cause infection. Th e long-term goal is to try to identify alternative substances that could be used for protection and/or treatment of Salmonella infections.
Professor Bergman’s research lab is a multidisciplinary lab that works in the disciplines of neuroscience, physiology, ethology, ecology, toxicology, histology, and pharmacology. Much of the research in the lab is accomplished using crayfish. Using crayfish for biomedical research may not seem immediately applicable when considering human health, but basic biomedical research it turns out is largely about understanding organisms and their interactions with other organisms. Humans as you know are extraordinarily complex on many levels, yet we only understand a small fraction of the interactions, structures, chemicals, and pathways in our bodies. Therefore the best way to determine the effect of a drug or disease on a living system is to study it first in an animal system. Drugs, vaccines and treatments in human medicine are largely based on years of physiological research with animals. To that end, the crayfish lab studies sensory system physiology, neurochemical modulation of aggression, neurogenesis via social enrichment, operant conditioning/learning, pollution effects on sensory receptors and development, nociception, growth/molting, orientation strategies when finding food or mates, the interactions of various invasive crayfish species, and feeding behaviors. A student becoming a member of his lab can expect to become knowledgeable in the scientific fields of neuroscience, animal behavior, physiology, biomechanics, toxicology, ecology, chemistry, and molecular biology.
Transcriptional regulation in the immune response
I am interested in understanding how the transcription factor, BATF, regulates gene expression in cells of the immune system. Although transcription factors are often thought of as proteins that turn on gene expression, BATF is a transcription factor that acts as a negative regulator. That is to say, BATF functions to suppress, or turn off, the expression of certain genes. However, we are still trying to understand the importance of this transcription factor in the functioning of the immune system. For example, when is BATF used and what genes does it regulate?
Recent evidence indicates that BATF may be involved in the inflammatory response in some way. The inflammation that follows injury can lead to resolution and healing or it can continue as a chronic inflammatory condition. We think that BATF may help determine which pathway is taken. We are working on a project in the lab that uses macrophages as a model for understanding when BATF is expressed and what genes it regulates. Macrophages are cells that are part of our natural defense system against foreign invaders such as bacteria or viruses. They are also intimately involved in the inflammatory response. We hope to show that BATF regulates genes in the macrophage that determine the choice between acute and chronic inflammation. This is important because although macrophages are a critical part of our defense against pathogens, they can also be detrimental in cases of asthma, allergy, cystic fibrosis, rheumatoid arthritis and other chronic inflammatory diseases because they "overreact" and cause more harm than good. By understanding the inherent controls (such as BATF) that govern the actions of these cells, new treatments may come to light for controlling aberrant responses.
General Research Interests
Identification of processes necessary for regulation of genes that are involved in signaling between photoreceptor cells and neurons in the visual system of the fruit fly Drosophila melanogaster, using a forward genetic approach. One gene known to disrupt signaling between these cells encodes the enzyme that synthesizes histamine, Histidine de carboxylase. We are currently examining the role of the Hdc gene in establishing when and where the neurotransmitter substance, histamine, is synthesized.
Current Research Projects include:
1) Analysis of developmental and tissue-specific regulatory regions of the Hdc gene. We are currently examining transgenic flies that contain a gene fusion between the upstream portion of Hdc (pHdc) and the enhanced green fluorescent protein (eGFP). We are studying whether the expression of pHdc-driven eGFP expression is identical to normal Hdc expression, through double immune labeling experiments for both histamine and eGFP. We are comparing the number of cells that contain eGFP to the number of cells that contain histamine, using fluorescence microscopy. It has been shown that histamine presence in cells is dependent on Hdc expression. We have recently determined that the upstream promoter region for the Hdc gene does induce eGFP expression in a number of cells, but not in all histaminergic cells. Work investigating which cells, throughout development are being marked with eGFP, is still ongoing. A second part of this effort is also nearing completion: that of constructing another Hdc-eGFP gene fusion, which contains the 3' UTR region of the Hdc gene placed adjacent to eGFP. Once completed, we may need to generate additional fusions between other control regions suspected to control Hdc expression, such as specific intronic regions surrounding the coding exons of the gene. The eGFP trasngenes generated can also be used to identify histamine-containing cells in vivo (either in the organism or in dissociated cell culture).
2) Examination of HDC protein maturation in vivo. The genomic region encoding the HDC protein has recently been engineered, being labeled with the epitope labels 6X-HIS and FLAG peptides, to study the biochemical regulation of the HDC protein. It has been proposed that the HDC protein undergoes several steps of protein processing prior to being active. Our intent is to identify the process of HDC maturation in vivo and locate where in the cell this occurs using these very specific and unique labels. This project will utilize established transgenic approaches to generate suitable genotypes for study, and likely will extend to the previously mentioned projects. We are planning to inject these newly constructed genes and then assay for their function shortly.
We are examining a molecule called GAP-43 which is a brain protein that is expressed in a wide variety of species including humans and has been shown to become biochemically altered in the process of learning and memory. Specifically, levels of phosphorylated forms of GAP-43 have been shown to increase following a controversial paradigm of learning and memory in several animals including rat, mouse and rabbit. We are interested to see if any differences in the profile of GAP-43 are associated with dementing illnesses that severely disrupt memory and learning. Since human brain tissue is difficult to obtain, we utilize brain tissue from a genetically altered mouse engineered to resemble Alzheimer's disease, a human neurodegenerative disorder characterized by profound cognitive impairment. Therefore, to test the hypothesis that the profile of phosphorylated isoforms of GAP-43 are changed in the brains of a mouse used to model Alzheimer's disease, GAP-43 will be examined by 1 and 2 dimensional SDS polyacrylamide gel electrophoresis. Isoforms of mouse brain GAP-43 will be detected by immunocytochemistry and silver staining and, further, quantified by computerized densitometry. Alterations in quantities of phosphorylated forms of GAP-43 might result from a pathological biochemical processes. Revealing molecular defects generates potential targets for the development of possibly more effective drugs to combat dementia.
My research program is somewhat unique in that there isn’t really an overarching disciplinary theme that all my work falls neatly under. My tendency is to seize on an interesting question (or set of related questions), recruit students to help answer it, then after a year or two move on to something (sometimes totally) different. Most of the projects in my lab, in one way or another, have employed molecular markers to infer past demographic and evolutionary events in populations of parasites and human pathogens. Past projects have looked at intragenic recombination in rotavirus, positive selection in viral hemorrhagic septicemia virus, and microevolution of rabies virus in Michigan bat populations. My students and I recently completed a project looking at the population dynamics of raccoon roundworm in West Michigan. And with colleagues in GVSU's Computer Science department, I recently collaborated on a project modeling Ebola diffusion in West Africa. Currently, my research students and I are studying social evolution among bacterial symbionts in an interesting tripartite system involving bacteria, nematodes, and insect hosts (some background here).
I am interested in the interaction between virus and host and the dance that ensues. Viruses have shaped all of us over time, whether in our genetic heritage or our current immune status. Our lab has looked at the endogenous retroviruses of sheep and goats and collaborated with labs asking questions on how animals might choose mates based on characteristics that serve as tells of their immune health. Recently we have shifted into bacteriophage as our system. Bacteriophage are of great interest these days as potential therapeutic agents, means of genetic manipulation, manipulators of the microbiome, players in ecological niches, and interactions with their host cells and organisms. Currently we are looking at questions of how they may affect the social interaction of bacteria, and isolating new phages from the environment.
In my lab we investigate the mechanisms involved in the nonenzymatic biological oxidation/reduction (Redox) reactions that are closely involved in physiologic and pathophysiological mechanisms. The working hypothesis is that the formation of an organic redox complex is necessary for electron transfer to take place. My investigations center on elucidating and understanding the mechanisms involved. To accomplish this, my students and I will be implementing biological, biochemical, spectroscopic and electrochemical techniques to characterize and describe the mechanisms of organic redox complex formation and the resulting transfer of electrons.
I am actively involved in both laboratory and field research. My current lab-based projects include assessing various aspects of hominin (e.g. humans, two species of chimpanzee, their ancestors, and the extinct lineages of their common ancestor) evolutionary anatomy through dissection and non-invasive Magnetic Resonance Imaging (MRI). Currently, I have been examining the insertion of the pectoralis minor muscle in the chimpanzee ( Pan troglodytes), as various interpretations of this attachment have been reported throughout the anatomical literature. Clarity of this issue is fundamental for not only understanding the evolutionary structural and functional pathway(s) of the muscle, but also for producing a better understanding the evolution of the hominin shoulder.
Another research area that I have focused on is assessing spatio-temporal variation of stress and developmental stability among extant and extinct mammalian taxa through fluctuating asymmetry (FA). The aim of this research area is to continue exploring the utility and advancement of FA to a variety of modern and prehistoric mammalian species. Deviations from symmetry in bilateral characters have achieved some prominence as measures of developmental (in)stability, revealing greater levels of asymmetry under adverse settings and mirrored target phenotypes under optimal extrinsic (environmental) and intrinsic (genetic) conditions. Increased FA has been associated with dietary, thermal, audiogenic and chemical stresses, but has been reported to decrease when genetic heterozygosity is elevated. Identifying the distribution and expression of FA among (paleo)species that have an extensive and well documented biological history (i.e. through time and space) provides a context for understanding how evolutionary processes and events potentially impact development.
My current paleobiological field research is situated within the Cradle of Humankind World Heritage Site, North-West Province, South Africa, at the fossil-bearing site of Luleche and in the adjoining Provence of Gauteng, at the fossil site of Hoogland. Notable excavations within the Cradle of Humankind and several in eastern Africa have produced rich samples of Pliocene and Pleistocene fossil mammals (including hominins), which have been a major source for interpreting our past. Such excavation and analysis of fossil assemblages from prolific sites has led to a wealthy and detailed understanding of a broader African paleolandscape. As important as these excavations are, the exploration of novel deposits, like Luleche and Hoogland, can only increase our understanding of the variability and richness of African (paleo)species, paleoecosystems, depositional processes, and evolutionary factors that existed in the past.
Medicine and Science in the Bible and in other Religious Texts
My primary research consists of exploring medical and scientific concepts in the primary sacred texts of the major world religions. The goal is to determine the role of medical knowledge in the formulation of laws and customs of traditional believers. For example, most people in the USA are familiar with the dietary restrictions mentioned in the Biblical books of Leviticus and Deuteronomy as well as in the Qur'an. My students and I have been looking at English translations of works in Christianity, Judaism, Islam and the Eastern religions to find and interpret these references. I am anxious to talk with students who have an interest in reading texts and in the history of medical thought as well as the relationship between science and religion.
I am also interested in compiling a history of the Biomedical Sciences Department and its variously named antecedents dating back to 1972 when the "School of Health Sciences" became the first unit at Grand Valley to have its focus on human biology and disease and wellness. I am interested in working with students who would enjoy searching the archives for material about their major academic unit and maybe uncovering an occasional skeleton in the closet.
Please contact me for more information at firstname.lastname@example.org or try to hunt me up in 102 LOH.
The role of calcium in endothelial cell induced mesenchymal cell differentiation
We showed previously that gap junction communication between mesenchmyal (MC) and endothelial cell (EC) is necessary for EC-induced MC differentiation, a process requiring activated TGF- . The current study investigated whether elevation of intracellular calcium (ionomycin 0.5 µM vs. vehicle control) is sufficient to stimulate differentiation (monitored as expression of smooth muscle -actin) of gap junction deficient MC in co-culture with EC or not. Ionomycin increased calcium in the MCs (~ 10 fold within minutes and ~ 4 fold at 1 hr) but resulted in no changes in -actin expression. In contrast, when ionomycin was added to EC/MC co-cultures, -actin expression by the MC was enhanced. Conditioned medium from ionomycin treated co-cultures also induced MC differentiation without increasing MC calcium, suggesting elevation of calcium in the EC induces formation of a soluble factor(s) responsible for inducing differentiation. Importantly, -actin expression was also elevated in MCs treated with medium conditioned by ECs alone. While the identity of the soluble factor (TGF- ?) awaits confirmation as does the mechanism whereby calcium causes its formation, these data argue that elevation of calcium in ECs stimulates the formation of a soluble factor(s) that acts in a paracrine manner to stimulate MC differentiation.
The main emphasis in my lab has been to isolate the cells that die during glaucoma in the eye, and then test drugs that may protect them. Previous work has examined the potential neuroprotective effect of drugs that selectively activate a specific type of nicotinic acetylcholine (ACh) receptor (the alpha7 nAChR), on retinal ganglion cells (RGCs) from the pig eye. Recently, we have followed that project with the examination of a selective modulator of alpha7 nAChRs. Other projects include the recording of physiological responses (ERGs) from the eye with/without drugs. Also we will be measuring the release of ACh from the eye & investigating which drugs increase the release of ACh to activate the alpha7 nAChR. Supporting projects include eye-cup studies which extend the neuroprotective studies on isolated cells in culture to the eye itself. Eventually, these results my lead to experiments in whole animals (e.g. rats). Another project in development has explored the possibility that drugs originally developed for Alzheimer's disease (AD) could be used for glaucoma. These AD drugs were originally designed to promote the maximal amount of ACh release in the brain.
I have just completed a study exploring the association of maternal restrictive feeding practices on the restrictive feeding practices of boys and girls and if this is modified by ethnic identity. Future research goals in this area are to conduct a pilot test to determine the feasibility and effectiveness of a feeding and physical activity intervention in mothers and their 8-12-year old daughters.
I am presently conducting a study with Dr. Beaudoin in Movement Science on middle class African American women with the goal of determining their diet quality, physical activity and the balance between these two variables.
The primary goal of our laboratory is to characterize the cellular and molecular mechanisms that regulate energy homeostasis and how disturbances in these regulatory mechanisms contribute to obesity. My lab is currently involved with the following project to address these long term goals.
Profiling Changes in Gene Expression in Response to Exercise & Aging
Obesity is a significant health concern as it is a major risk factor associated with increased morbidity and mortality from several chronic diseases including: cardiovascular disease, non-insulin dependent diabetes mellitus, some types of cancer, gallbladder disease, osteoarthritis, and hypertension. Despite the perception that the American public is increasingly concerned about consuming a healthful diet, the percentage of overweight individuals in the US continues to increase. Currently, 66% of adults over 20 years of age in the U.S. are considered overweight or obese. Current treatments for obesity are only moderately successful. Macroarrays and real time PCR are being utilized to profile changes in gene expression that occur in response to endurance training and aging in rats. Endurance training has been shown to result in consistent, but modest reductions in total fat mass, even when total body weight is not reduced. Aging, on the other hand, is consistently associated with an increase in fat mass. Developing a better understanding of the cellular adaptations that occur in adipose tissue in response to training as well as aging will allow a better definition of training protocols to maximize fat loss and may lead to the development of novel pharmacological treatments that maximize lipid oxidation and fat loss during physical activity or calorie restriction, and/or attenuate age associated increases in obesity.
Develop research with breadfruit not only as an alternative but also as a "functional food" product for the public. Other research interests include testing the reliability and validity of feeding tools for infants and adults and currently investigating DHA consumption in women of Hispanic origin.
My research interests center around a functional, real-time measure of neurotransmission. Neurons send and receive information through chemical means, transducing electrical signals into chemical signals. These transmissions occur on a very fast time-scale, in the millisecond time frame.
One of the best methods for monitoring neurotransmission in real time is called Fast-Scan Cyclic Voltammetry (FSCV). Fast-scan because it is happening fast: every 100 ms; cyclic because it happens repeatedly; and voltammetry because it deals with voltage changes. In brief, when a carbon surface reaches a certain voltage, and a neurotransmitter is next to it, the neurotransmitter will oxidize (like metal rusting). You can measure this reaction and use it to look at changes in neurotransmitter concentration.
The goal of my lab is two-fold: 1) continue to improve neurotransmitter recording techniques, and 2) to classify and understand neurotransmission in the crayfish. Crayfish communicate through chemical means, but little is known about their neurotransmission in real-time, or what neurotransmitters are released, if any, during confrontation. Using FSCV to measure crayfish neurotransmission will allow us to better understand this organism and how it communicates with others. Currently my research is focused on enhancing electrode sensitivity, with crayfish work to occur in 2013 or 2014.
Cranial suture closure timing and pattern using current medical imaging techniques
The timing and pattern of human cranial suture closure has been used for a disparate range of practical purposes. Forensic anthropologists commonly use the timing of the fusion of cranial sutures to determine age-at-death of individuals, albeit with limited success. Some physical therapists use the patency of cranial sutures to perform craniosacral therapy - a therapy that claims to relieve problems (headaches, chronic back pain, etc.) attributed to changes in the "rhythmic movements" of the cerebrospinal fluid by manually manipulating the bones of the cranium. Both the forensic and therapeutic applications of cranial suture biology have a number of detractors - there is significant doubt about the scientific foundation of their practice. Currently, all of the gross descriptive data of the closure of cranial sutures used in forensic and therapeutic techniques are from simple, direct observation. Current medical imaging techniques, however, can give a better picture of the gross development and maturation of cranial sutures, and perhaps settle some of the debate. My current project is the determination of the timing and pattern of suture closure using existing CT scans. This project will lay a better foundation for future practical applications, and allow a serious evaluation of current ones.
Role of the tetraspanin protein CD82, in c- Met regulation in metastatic prostate tumors.
My research interest is in the field of prostate cancer, in identifying the role of a metastatic tumor suppressor protein called CD82 (KAI1 gene). CD82 expression is lost during prostate tumor progression to metastasis. Loss of CD82 expression has also been recently shown to correlate with metastasis in a number of invasive cancers. The mechanisms by which cancers become metastatic are not clear. CD82 has been shown to associate with membrane proteins such as integrin and receptor tyrosine kinases (EGFR, Met). During my postdoctoral work at the VanAndel Institute, I have re-expressed CD82 to normal levels in metastatic prostate tumor cell lines. Re-expression of CD82 in these tumor cells reduced invasion in vitro , and suppressed integrin- or HGF-mediated activation of the receptor tyrosine kinas c-Met. Conversely, we have also shown that suppression of CD82 expression in normal cells increases integrin mediated c-Met activation. Signaling through c-Met is required for cell migration and invasion in metastatic prostate tumor cells, which is over expressed in all metastatic prostate cancers. The exact mechanism by which CD82 regulates c-Met is my current research focus. Preliminary data suggests that CD82 may be causing either a decrease in c-Met cell surface aggregation or may be bringing in a c-Met specific phosphatase in close proximity, and thereby regulating c-Met phosphorylation/ activation. There is indication also that CD82 may be regulating one of the four phosphorylation sites that are required for activation of Met. Both these mechanisms of CD82 regulation and the significance of the regulation of one specific phosphorylation site in Met are currently under investigation.
Another project in the lab is involved in analyzing the difference in gene expression between prostate cancer cells with or without CD82 using Agilent micro array technology. Two clones of PC3 cell lines, one transfected with a vector (PC3-5V) and another with CD82 cDNA (PC3-29) were analyzed using micro array Agilent technology. The micro array data was analyzed using a Limma-R program to identify the genes regulated by CD82. The micro array analysis is complete and we are currently looking at the top ten genes that are statistically significant and analyzing the significance of the up and down-regulation of these proteins in these cells. The results are being further validated by RT-PCR and western blot analysis. In addition more (prostate tumor) clones expressing CD82 and normal prostate cells with or without CD82 (by CD82 siRNA) will also be analyzed to reconfirm the results.
Coronary arteries supply blood to the myocardium and they are the site of various metabolic pathways, including those involving redox reactions. When redox reactions become poorly regulated, free radicals and other reactive oxygen species are released in coronary arteries, leading to increased oxidative stress. Previous studies indicate that free radicals play a role in the genesis of cardiovascular disease. Our objective was to evaluate the role of superoxide in altering the vascular reactivity of coronary arteries. We hypothesized that a potential non-enzymatic redox reaction between vitamin C and imidazole results in the production of superoxide, which impairs vascular reactivity. We conducted isometric force measurement studies to assess changes in vascular reactivity. The combined effect of vitamin C and imidazole induced a significant change in the vascular reactivity of the arteries. To further confirm the release of superoxide, a fluorescent dye based dihydorethidine assay was carried out to measure the levels of superoxide released in the arteries. The images and average intensity values of stained nuclei suggested an increase in the superoxide levels in the arteries incubated in vitamin C and imidazole, though the average intensities were not statistically significant (p=0.11). This may be due to the small sample size (n=13), thus future studies will include additional experiments to determine if superoxide production is significantly elevated. If successful, these studies may provide basic information on non-enzymatic sources of superoxide in the vasculature.
I'm broadly interested in the evolution of locomotor diversity in primates. To that end, my current research interests can be divided into three projects. First, my research uses three-dimensional geometric morphometrics (analysis of shape in three dimensions) to examine patterns of postcranial variation in the forelimb and hindlimb of human ancestors. I am using this data to investigate the underlying processes that drive shape variation in the postcranial skeleton of humans (e.g., patterns of integration/modularity and potential ontogenetic shifts) and the environmental factors that could have been instrumental in past selective events.
Second, I have been working in collaboration with scientists at the Institut Català de Paleontologia Miquel Crusafont (ICP) in Barcelona, Spain on functional analyses of the Middle-Late Miocene (approximately 9-12 million years ago) hominoids from the Vallès-Penedès Basin in Catalonia. Miocene apes are interesting in that their morphology can illuminate the progression of the acquisition of adaptations for modern ape locomotor patterns, including bipedality in humans. Finally, I am investigating the evolution and diversification of new world monkeys in collaboration with a multi-national, multi-institutional team. Fossil new world monkeys are interesting from a paleontological standpoint because there are many unanswered questions about their relationships to both the extant radiation of new world monkeys and to contemporaneous fossil taxa in Africa, Europe and Asia. Fossil new world monkeys are also of particular value because the modern monkeys are extremely diverse in their locomotor repertoires, but genetic evidence indicates a single taxon for the origin of the living groups with deep divergence dates for the modern lineages. Thus, they present an interesting test-case for examining the process of locomotor modification and diversification in primates. We are also currently investigating re-opening paleontological expeditions at two different sites in South America, as well as continuing work at sites in the Caribbean to add to fossil evidence for this group.
Our group uses the chicken and mouse embryo as model systems to determine how neural stem cell differentiation is influenced by intrinsic factors (such as gene expression) and extrinsic factors (such as factors secreted by other cells). The accessibility of the chick embryo to experimental manipulation allows us to screen for the effect of experimental manipulation on stem cell differentiation using quantitative PCR and anatomical approaches. With this approach, undergraduate and master's level students have determined that the basic helix loop helix protein Nato3 is sufficient to promote expression of markers for dopamine producing neurons. The clinical significance of this finding is that dopamine neurons are the target of degeneration in the pathophysiology of Parkinson Disease, so our current studies are focused on understanding the mechanism of this effect with the hope of informing therapeutic strategies towards this disease.
Additionally, our lab is using the same model system to analyze the effect of factors outside of the neural stem cell (cell-extrinsic factors) such as polyunsaturated fatty acids. These factors have been shown to be important signaling components in development and can affect stem cell differentiation in culture, but have not been analyzed in the living embryo.
My research focuses on using C. albicans as a model fungal pathogen. C . albicans is a frequently acquired nosocomial infection both within the US and worldwide. It is an increasingly common threat to human health as a consequence of AIDS, steroid therapy, organ and tissue transplantation, cancer therapy, broad spectrum antibiotics and other immune defects. These infections carry unacceptably high morbidity, mortality rates (30-50%) and important economic repercussions (estimated total direct cost of approximately 2 billion dollars in 1998 in US hospitals alone).
The objectives of my research are: ( i) the application of state-of-the-art yeast cell biology and genetics to the study of Candida albicans pathogenesis and commensalism, ( ii) the use of proteomics, genomics, and bioinformatics in the analysis of the lifecycle of C. albicans, ( iii) studies of C. albicans virulence in vivo, and ( iv) signal sensing and transduction particularly with reference to disease related and quorum sensing pathways in C. albicans.
My research aims to understand the social, ecological, and physiological factors driving primate behavior. I integrate observational field-based methods, controlled captive experiments, and laboratory approaches to holistically investigate both the proximate and evolutionary explanations for primate behavior. I am currently pursuing several projects relating to this research theme.
Firstly, I am interested in how the spatial and temporal distribution of food influences the competitive regimes in which primates live. To test these questions I am currently working with wild marmoset monkeys in Brazil which exploit both renewable and depletable food resources. I am also interested in this species' use of olfaction to communicate information about food resources. A second branch of my research investigates how primates use behavior and physiology to respond to their thermal environment. This research is being conducted on wild howling monkeys in Costa Rica. I have also done extensive work into the social behavior of white-faced saki monkeys. This species displays variation in social system, with some groups being pair living and monogamous, while others have multiple adults and practice polygamy. I am broadly interested in the ecological, demographic, and physiological factors that drive this variation in social system.