Lisa Bain, Department of Biological Sciences
Examining toxicant-induced changes in stem cells. We are interested in understanding how early life exposure to a chemical results in lifelong consequences, such as changes in growth and behavior. Arsenic is a common contaminant found in water and some crops, and the laboratory is trying to determine the mechanism by which it can inhibit the differentiation of stem cells. For this project, students will be working with killifish, a small estuarine minnow, that were exposed to arsenic as embryos. They will help examine changes in feeding behavior and locomotion, and then examine different populations of stem cells in the intestines, brain and muscles using a variety of staining techniques. Students will be involved in all aspects of the work, including rearing the fish, behavioral tests and staining the tissues.
William Baldwin, Department of Biological Sciences
Interplay between toxicants and high-fat diets in perturbing the allocation of lipid resources and inducing obesity. My research focuses on an organism’s ability to acclimate to environmental stressors such as foreign chemicals and toxic endobiotics. Nuclear receptors such as CAR and PXR in mammals and HR96 in invertebrates are important in inducing protective enzymes and helping organisms acclimate to environmental stressors. Detoxification enzymes induced by these xenobiotic-sensing nuclear receptors include the cytochrome P450s (CYP). This enzyme family is often the first step in the metabolism of toxic chemicals; however, CYPs may activate some chemicals. We use a variety of techniques including lifecycle testing, transactivation assays, transgenic technologies, bioinformatics, and transcriptomics to study how organisms adapt to toxicants. We are using newly constructed knockout and humanized mouse models to determine how animals respond to toxicants. Recent work also includes investigating the interplay between high fat diets and toxicant exposure in the development of fatty liver disease and obesity in mouse models, and allocation of dietary resources in Daphnia magna. During the summer research project, students will treat animals with a specific unsaturated fat or toxicant under a couple of different conditions and associate the physiological impacts (i.e. reproduction, growth) with changes in lipid profiles and changes in gene expression. During the course of this project, the student will learn basic concepts in life cycle assessments, nuclear receptor signaling, and a variety of metabolism and molecular biology techniques. The student will participate in all lab activities, including weekly lab meetings, journal discussions, and will work closely with other members of the laboratory.
Douglas Bielenberg, Department of Biological Sciences
Does the anatomy of a pre-fertilized peach ovary correlate with final fruit size? Speeding breeding of new peach cultivars requires genetic markers for fruit size. Currently, potential fruit size can only be evaluated after trees reach reproductive maturity and expensive cultural conditions for optimum fruit quality are maintained. Studies of other fleshy fruits, such as tomato, suggest that variation in fruit size can be influenced by ovary cell number prior to fertilization. We are using histology to evaluate variation in ovary size and cell number in trees from the Clemson University peach breeding program. Ultimately, we will use this data to identify genetic markers for ovary cell number (and fruit size) which can be used for the marker assisted breeding of improved peach cultivars.
Barbara Campbell, Department of Biological Sciences
We investigate the diversity, interactions and function of microbes in diverse habitats as well as the effect of anthropogenic influence on these ecosystems. Since the majority of microbes cannot be cultured, we study these microbial communities by combining molecular detective work with careful physical and chemical assessment of the habitat in question. Habitats we currently study include: estuarine, streams/lakes and associations between seagrass dwelling clams and their symbionts. The molecular detective work includes utilizing a combination of PCR, qPCR as well as metagenomics/metatranscriptomics to assess population and community properties and functions within the habitat under study. Depending on the project, REU students would have a chance to do field work, investigate the diversity and/or functions of the microbes in the chosen habitat, and learn cutting edge bioinformatics and statistical analyses.
Susan Chapman, Department of Biological Sciences
Autism Spectrum Disorders. The focus of the lab is to understand neurodevelopment and associated disorders; that is, the mechanisms that lead to formation of an adult animal from a single fertilized egg cell and elucidating the mechanisms involved when development goes awry. We are interested in the developing zebrafish, Danio rerio, which is a model genetic system for studying vertebrate development. Zebrafish have yielded many insights about neurodevelopment through gain and loss of function studies. In order to produce mutants, we inject morpholinos into one cell stage embryos and observe the morphological and behavioral effects on development. We also determine the molecular mechanisms and neural circuitry in neurodevelopmental disorders. We also use the CRISPR/Cas9 gene editing system to produce permanent changes in the genome of fish, resulting in novel transgenic fish strains. Our ultimate aim is to develop treatments for autism spectrum disorders that result from single gene mutations.
Zhicheng Dou, Department of Biological Sciences
My lab focuses on nutrient metabolism in Toxoplasma gondii, a human protozoan pathogen. Toxoplasma parasites are obligate intracellular parasites that can infect virtually any warm-blooded animals. Infected populations are widely distributed geographically, with about one-third of the human population harboring the parasite. Although the infection is often benign in normal individuals, it can cause severe, even lethal, disease in immunocompromised people or organ transplant patients. Recent studies implicating chronic infection as a potential risk factor for mental illnesses warrant a new push toward identifying vulnerable targets in the parasite. Intracellular growth of T. gondii requires the parasite to access host metabolites to support its replication. Our recent findings have revealed that Toxoplasma parasites can ingest host proteins and digest them in a lysosome-equivalent structure to support their replication.
Using a combination of molecular biology, biochemistry, and cell biological approaches, my laboratory will study the mechanistic underpinnings of acquisition and utilization of host macromolecules by Toxoplasma through its ingestion pathway. I also plan to use the sophisticated systems biology and metabolomics strategies to comprehensively dissect metabolic pathways in Toxoplasma parasites. The work is not only important for understanding how parasites acquire nutrients from host cells, but also to identify targets in the parasite nutrient pathway that may be susceptible to therapeutic intervention. Knowledge gained from T. gondii will complement nutrient metabolism in other human pathogenic apicomplexan parasites lacking facile genetics, such as Plasmodium and Cryptosporidium.
David Feliciano, Department of Biological Sciences
Project: Intercellular transfer of extracellular vesicles during corticogenesis. Elaboration of the cerebral cortex requires exquisite coordination of cellular events between distinct germinal stem cell pools. A goal of our laboratory is to determine how intercellular signals coordinate corticogenesis. We recently found that small secreted extracellular vesicles known as exosomes are abundant within the cerebrospinal fluid (CSF) of the fetal brain. CSF exosomes are subject to age dependent declines, are secreted from choroid plexus epithelial cells, and regulate embryonic neural stem cell proliferation. We are generating a transgenic mouse that will express conditional fluorescent extracellular vesicles. In this REU project, the selected student will use a combination of genetic manipulations and confocal microscopy to help generate a map of extracellular vesicle exchange in the developing brain. The project will emphasize technical and critical thinking skills required for graduate school. The student will have the opportunity to interact with lab personnel and to present findings during regularly scheduled laboratory meetings.
Julia Frugoli, Department of Genetics and Biochemistry
My lab focuses on understanding how the shoots and roots of plants communicate with each other at the molecular level (how the plant “thinks”), using mutants in a process called nodulation to determine what genes and proteins are involved in long-distance signaling. The project involves DNA, RNA, and protein work as well as mapping & cloning genes.
The formation of nitrogen-fixing nodules in legumes is tightly controlled by a long-distance signaling system in which nodulating roots signal to shoot tissues to systemically suppress further nodulation. We previously identified several mutants in Medicago truncatula that lack the ability to regulate nodule number from the shoot (sunn and lss) or from the root (rdn1). In each of these cases we were able to characterize the mutation and clone the gene, allowing us the build a model of how the plant regulates the number of nodules it forms. To complete the model we have focused on identifying more mutants that affect nodule regulation, as each new gene allows us to refine the model. This project focuses on generating, cloning and characterizing these unnamed mutants which presently have only internal laboratory number identifiers using several approaches:
1) Identifying phenotypes in T-DNA insertion mutants identified as carrying an insertion in a gene of interest to us, and if one is found, segregating that insertion away from the rest of the insertions to confirm it causes the observed phenotype.
2) Creating mutants that interact with mutants we already have. A very successful strategy in the lab has been to perform suppressor screens-remutagenize a nodulation mutant to identify second mutations that make the mutant normal again. These second mutations are usually in the same pathway. We have done this successfully with the SUNN gene and we have several suppressors of the SUNN mutation that need to be mapped and cloned. This portion of the project is long term, so it will involve working closely with senior students in the lab.
3) Characterizing phenotypes of the mutants through PCR measurements of gene expression, physiological tests, and interactions with already published mutants.
Cheryl Ingram-Smith, Department of Genetics & Biochemistry, Eukaryotic Pathogens Innovation Center (EPIC)
My laboratory studies metabolism in Entamoeba histolytica, a eukaryotic pathogen that causes amoebic dysentery in ~90 million people each year. Many studies on E. histolytica metabolism have focused on glycolysis, the initial pathway used by most organisms to breakdown glucose, which is a favored energy source. However, this parasite colonizes the large intestine where glucose is very limited, and must thus adapt to using alternate energy sources. The REU student’s project will be related to this larger goal of understanding how E. histolytica adapts to thrive in the low glucose environment of the large intestine. The student will investigate one of the pathways that are proposed to play a role in this adaptation, with a particular emphasis on one or two enzymes that would be expected to regulate the overall function of the pathway. The student will work under the direction of the PI mentor with assistance from graduate students in the lab to learn laboratory techniques and to use equipment. The student may learn and apply many the following techniques: culturing and measuring growth of the parasite under different conditions, isolation of DNA and RNA, PCR and molecular cloning, reverse transcriptase PCR to examine RNA levels, production and purification of recombinant proteins, and enzymatic assays.
Miriam Konkel, Department of Genetics & Biochemistry
Mobile elements in primate genomes
One focus of my laboratory centers upon the ‘mobilome’ (the global mobile element content of a genome) and analyses of primate genomes. We are interested in how genomes evolve with respect to mobile elements, and how mobile elements evolve over time. One facet of these whole genome analyses is the identification and characterization of new repeat families. Examples include our co-discovery of the gibbon-specific LAVA, and discovery of the New World monkey-specific Platy-1 repeat families.
A second, synergistic focus of my laboratory is the development of cyberphysical genomics interfaces. In an interdisciplinary team, we are developing new approaches for data interaction through integration of tablets, interactive walls, and tangible user interfaces. Novel approaches for data interaction of large datasets (e.g. several to thousands of genomes) will lead to a better understanding of datasets.
Depending on the interest of the REU student, s/he will either work on the computational identification and characterization of mobile elements in primates or the development of cyberphysical genomics interfaces. If desired, a project at the intersection of interface design and mobile element research is also an option.
Lukasz Kozubowski, Department of Genetics & Biochemistry
Microbial pathogens utilize a variety of strategies to facilitate survival in the infected host. One of the most important mechanisms is the ability to respond to stress and adapt to an adverse host environment. Therefore, inhibiting stress response pathways constitutes a promising antimicrobial therapy.
We study a human fungal pathogen Cryptococcus neoformans to understand the cellular processes used by pathogenic microorganisms to allow survival in the infected host. C. neoformans is a major opportunistic fungal pathogen worldwide and a leading cause of morbidity and mortality in AIDS patients. Our work with C. neoformans has led us to hypothesize that this pathogen has evolved unique ways to control cell division in a manner that allows it to survive within a human host. Testing this hypothesis would provide insights into how eukaryotic pathogens adapt to the host environment and could potentially reveal new targets for therapeutic interventions.
One of the main research themes in our laboratory concerns the biology of septin proteins. Septins form filamentous structures at sites of cell division and contribute to cytokinesis. Cytokinesis is the process that separates the cytoplasms between dividing cells during mitosis. While in all animal and fungal cells septins participate in cytokinesis, in some species septins are not essential for this process. Elucidating how septins contribute to cytokinesis is the key to our understanding of how organisms evolved to adapt diverse mechanisms of cell division. We have recently shown that the septin complex in C. neoformans is not required for cytokinesis to occur at 24°C, which is in contrast to the well-established essential role of septins in bakers yeast. However, septins become essential at 37°C. The findings that septins are only conditionally essential in C. neoformans suggest that they may primarily contribute to a fidelity mechanism that is needed to assure that cytokinesis works under stressful conditions. Our main objective is to identify and characterize components of cytokinesis in C. neoformans with an emphasis on the role of septins in stress response.
Amy Lawton-Rauh, Department of Genetics and Biochemistry
Genomics of domestication and ferality: crops, wild relatives and weeds. How does breeding impact the genomes of crops during domestication and post-domestication stability? What can we learn and use from crop wild relatives and locally adapted weeds to improve the sustainability of bioproduct, food, fuel and fiber production along with models of how fast species can adapt to changing environments? These are important questions that help us translate genomics models into tools that improve how agriculture impacts food security, human health and ecosystems impacted by production. We study the relationships between genome dynamics, domestication and ferality traits, genetic histories of crop-wild relative lineages, and the impact that these relationships have on crop improvement and agroecosystems (including weedy and invasive species). More specifically, we study genome-wide diversity in crop wild relatives and diverse seed collections of rosaceous crops (esp. peaches, apples and cherries) to combine disease resistance and desirable market qualities, the genome dynamics underlying aggressive rapid origins and proliferation of herbicide-resistant weedy Amaranthus species, and the roles of domestication and de-domestication/ferality in Oryza spp. (rice).
Research interns meet with the PI on a regular basis to firstly design project details tailored to individual interests (while connecting directly to ongoing publishable projects) and regularly for research progress/changes and career mentorship. During summer 2017, NSF REU interns in the lab will also work with a postdoctoral research associate, PhD Genetics students, and other undergraduate research interns in the lab for an enriching and highly engaging research experience ultimately leading to a poster presentation and talk that can be presented in the future. Interns in my lab have several options and combinations of tools that they can use for their projects, ranging from bioinformatics analyses of genome data, performing genetic crosses in the greenhouse to study the relative roles of genetics versus the environment in key traits, and employing computational genomics tools to determine the domestication origins and histories of crops and weedy species (especially herbicide-resistant species) using empirical data from Rosaceous crops and wild relatives (peaches, apples, cherries, strawberries), Amaranthus species (highly herbicide resistant), and rice.
Hong Luo, Department of Genetics and Biochemistry
Abiotic stress, such as water deficiency, salinity, heat, cold, and nutrition starvation, is a major limiting factor in plant growth and will soon become even more acute as desertification covers increasingly more of the world's terrestrial area. Drought and salinity are already widespread in many regions, and are expected to cause serious salinization of more than 50% of all arable lands by the year 2050. They are therefore among the most important targets for improvement in crop plants. Multiple biological pathways have been implicated in regulating plant response to abiotic stress. Agricultural biotechnology manipulating expression of genes involved in plant stress response and aimed at crop genetic improvement for enhanced adaptation to abiotic stresses has huge economical impact.
The research in my lab focuses on understanding molecular mechanisms underlying plant response to adverse environmental conditions. Using genetics, molecular biology and genomics tools, and taking advantage of recombinant DNA and transgenic technologies, we seek to identify and functionally characterize new components in plant signal transduction, non-coding small RNA molecules, such as microRNAs (miRNAs), and other genes and biological pathways involved in regulating plant stress response. The knowledge acquired allows us to design novel molecular strategies to genetically engineer various food and bioenergy crops and perennial grasses, including turfgrass, switchgrass, rice, soybean and cotton for enhanced performance under various environmental adversities. Using biotechnology approach for trait modifications in economically and environmentally important crops, our long-term goal is to genetically improve major crop species and develop new cultivars with significantly enhanced yield and quality, contributing to agriculture production.
Meredith Morris, Department of Genetics & Biochemistry, Eukaryotic Pathogens Innovation Center (EPIC)
We work on Kinetoplastid parasites, which cause African trypanosomiasis, Chagas Disease and Leishmaniasis. Treatments for these diseases are insufficient and the increasing development of drug-resistance make finding new drug targets essential. We work to define molecular pathways that regulate parasite specific biology. Such knowledge is essential in the development of treatments that kill the parasite and reducing the effects on the host.
Kinetoplastid parasites have unique organelles called glycosomes that compartmentalize metabolic pathways. They are essential to parasite survival but our limited knowledge about their biology hinders our ability to exploit these organelles for therapeutics. We use a number of experimental approaches to learn about how these organelles are made, how they multiply, and how they respond to environmental and developmental cues. Understanding these processes will reveal new pathways that contain novel drug targets.
REU students will be involved in generating recombinant proteins for in vitro binding assays, making transgenic trypanosome cell lines to follow the localization of glycosome proteins under different environmental conditions, and participating in lab meetings.
Kimberly Paul, Department of Genetics & Biochemistry, Eukaryotic Pathogens Innovation Center (EPIC)
My lab focuses on the role of lipid metabolism in pathogenesis in trypanosomes, which are protozoan parasites that cause disease and death in humans and animals. In particular, we focus on fatty acid metabolism for two reasons: (1) fatty acids are the major constituent of the plasma membrane, which is the part of the pathogen directly contacting the host environment and the major site of immune attack; and (2) the major surface coat proteins of the parasite are anchored to the plasma membrane by fatty acids and they are directly involved in immune evasion. We use molecular, biochemical, and cell biological approaches to examine all the major pathways by which the parasite supplies itself with fatty acids: fatty acid synthesis, fatty acid uptake, and the mobilization of fatty acids to/from storage organelles known as lipid droplets. We also examine how these different fatty acid metabolic processes are involved in immune evasion and pathogenesis. REU students will have their very own project in one of these three major areas (synthesis, uptake, storage). For example, s/he might characterize a potential fatty acid uptake mutant by performing fatty acid uptake assays.
Kara Powder, Department of Biological Sciences
The goal of our work is to understand the mechanisms that control facial development, and to identify the genes that regulate facial variation and facial anomalies, which occur in 1/3 of all congenital birth defects. As models, we use zebra fish and cichlid fishes. Cichids show an amazing range of craniofacial morphologies, which correlate with their feeding mechanism, e.g. algae scraping or suction feeding. In both cichlids and zebra fish, we combine genetic methods with gene manipulations in embryos to determine how changes in gene expression and function affect development to make faces that look different. Students will be involved in all aspects of the project, which may include fish rearing, DNA genotyping via PCR, in situ hybridization, DNA cloning, genetic engineering via the CRISPR/Cas9 system, and experimental embryology via embryo injections.
Charles Rice, Department of Biological Sciences
Maintaining proper circadian rhythms, responding to low oxygen levels, regulating cell cycle steps, and sensing and responding to potentially dangerous environmental chemicals are just a few physiological roles of a unique collection of proteins known as the basic loop-helix-loop/Per-ARNT-SIM (bHLH-PAS) family of proteins. This is an ancient group of genes and proteins dating back to very early life forms on planet Earth. As with many sensory systems, in both individual cells and integrated whole organisms, there is feed-back control to maintain a balanced system. Under extreme conditions, such as harsh chemical environments (heavy pollution), severe hypoxia (e.g., brain damage, cardiovascular disease, sustained low environmental oxygen), prolonged darkness or lighted conditions, and even under heavy cancer burden and chronic inflammation, this integrated balance between members of the bHLH-PAS superfamily fails, leading to severe and life threatening disease. Our lab has developed a large tool-box of genetic and protein probes for various members of the bHLH-PAS superfamily of proteins to study their expression and interactions under experimental conditions using three systems; a fish model, the mouse model and a wide assortment of cell lines. This particular project will focus on how the aryl hydrocarbon receptor (AhR), the AhR-repressor (AhR-R), aryl hydrocarbon receptor nuclear transporter (ARNT) and hypoxia inducing factor (HIF-α) interact to maintain homeostasis of the immune system under low environmental oxygen levels, exposure to environmental pollutants and during the progression of cancer.
Vincent Richards, Department of Biological Sciences
Identification of genetic determinants for bovine mastitis: towards a bacteriostatic mastitis therapy for gram-positive bacteria as an alternative to bactericide antibiotics.
Bovine mastitis is the major production limiting disease in the US dairy industry, with losses approaching two billion dollars/year. The major gram-positive species responsible are Streptococcus agalactiae, Streptococcus uberis, Streptococcus dysgalactiae subsp. dysgalactiae and Staphylococcus aureus. Bactericidal antibiotics are used extensively as treatment. However, bactericides produce strong selection pressure for resistance, which is a serious impediment to the treatment of infectious disease. Promising alternatives are bacteriostatics that control infection by inhibiting growth, and therefore minimize evolution of resistance.
The long-term goal of this research is to develop a bacteriostatic mastitis therapy for gram-positive bacteria. This goal is motivated by the problems associated with bactericides and also because some gram-positive mastitis pathogens respond poorly to conventional treatment. Towards this long-term goal, this research will use transcriptomics to identify genes required for growth in the bovine mammary gland that will serve as targets for such a therapy. Transcriptomics is the application of modern DNA sequencing technology to measure relative levels of gene expression. In this project, transciptomics will be used to determine genes that are highly expressed for each of the major gram-positive species when they are grown in bovine milk.
William Richardson, Department of Bioengineering & Institute for Biological Interfaces of Engineering
May the force be with you! Interplay of stiffness and stretching to modulate fibroblast behavior.
Our Systems Mechanobiology Lab is interested in cell-matrix mechanobiology and two broad questions:
1) How do our bodies respond to mechanical stimuli across molecule, cell, and tissue scales?
2) How can we control cell-matrix mechanobiology to diagnose, treat, and prevent disease?
In line with those questions, this REU project will explore how fibroblast cells respond to their local tissue stiffness and their local tissue stretching, and whether they are more sensitive to one vs. the other. Cells will be grown in the lab on surfaces with controlled stiffnesses and stretches, and various biological assays will be used to measure cell responses such as proliferation, protein expression, and cytoskeletal remodeling. The resulting cell behaviors will then be incorporated into an existing computer model that our lab has helped develope to design new drug strategies for fibrotic diseases.
Michael Sears, Department of Biological Sciences
What are the proximate causes of decreased body size in salamanders in response to climate change? Understanding how organisms respond to climate is one of the biggest challenges faced by ecologists. Our group has reported widespread reductions in body size for several species of terrestrial, woodland salamanders over the past 50 years. These changes have likely resulted from warming climates in the southern Appalachians. To understand changes in body size, students will perform laboratory experiments that expose Plethodon salamanders to historical, contemporary and future climatic conditions. During these experiments, students will track changes in body size, metabolism, feeding and water loss. Students will also collect tissue samples for transcriptomic analysis. By linking physiology to gene expression, students will gain experience with cutting edge approaches in physiological ecology. Students will work with graduate and undergraduate students on a regular basis, including lab meetings and a weekly journal club. Students will also present their results at a national meeting.
Michael Sehorn, Department of Genetics and Biochemistry
DNA double strand breaks are the most deleterious form of DNA damage. A single unrepaired DNA double strand break can result in cell cycle arrest and cell death. The repair of DNA double strand breaks occurs by two major pathways known as non-homologous end joining and homologous recombination. While non-homologous end joining is error prone, homologous recombination is mostly error free. Defects in homologous recombination can result in chromosomal aberrations that often manifest as cancer. My laboratory is interested in the molecular mechanism of homologous recombination. The REU student will use various biochemical and genetic approaches to investigate the mechanism of homologous recombination in both human and yeast model systems. The student will have the opportunity to learn a number of techniques including PCR, site-directed mutagenesis, protein purification, and design and implementation of biochemical assays.
Rajandeep Sekhon, Department of Genetics and Biochemistry
We are using a systems genetics approach involving genomic and transcriptomic analyses to identify and characterize genes and genetic elements responsible for controlling senescence—the process of programmed death—in maize. We are examining senescence phenotypes and correlating those to genotypes to better understand how maize plants undergo death, and to possibly delay the process. Our findings will inform the generation of dual-purpose plants for biofuel and food production with longer periods of productivity due to delayed senescence. Students will be investigating genetic mutants that have shown interesting senescence phenotypes using a forward genetics approach to map the gene responsible for the phenotype and ultimately clone the gene. The students will be extracting DNA from plant tissue, performing polymerase chain reactions (PCR), and mapping the location of the mutation based on PCR results. They will be performing these tasks in the field (to collect sample tissue), in the lab (to extract DNA and run PCR), and using bioinformatics tools in silico (to generate maps locating the position of the mutation in the maize genome). Students will also be working in the field together with the mentor, graduate and undergrad students, and research associates to get hands-on training on field experimentation including making genetic crosses and collection of phenotypic data. Students must be willing to work in corn fields located at the Clemson University Experiment Station near campus during the period of their training. Mentor will provide transportation.
Dr. Kerry Smith, Genetics and Biochemistry, Eukaryotic Pathogens Innovation Center (EPIC)
Fungal infections cause one million deaths annually, accounting for nearly 50% of all AIDS-related deaths. The basdiomycetous fungus Cryptococcus neoformans is an invasive pathogen of the central nervous system and the most frequent cause of fungal meningitis resulting in more than 625,000 deaths per year worldwide. Exposure to C. neoformans is common, as it is an environmental fungus found in the soil and can enter the lungs through inhalation. During infection in the lungs, C. neoformans cells are engulfed by macrophages. If the macrophage fails to kill the fungal cells, they will survive and replicate within the macrophage. Active infection in the lungs results in pneumonia, and the macrophage may then serve as a means of transit for Cryptococcus to migrate to the central nervous system and cross the blood-brain barrier to cause fungal meningitis. An increased rate of infection occurs in individuals with impaired cell-mediated immunity, particularly those with AIDS and recipients of immunosuppressive therapy.
To be able to survive, C. neoformans must be able to adapt to changing environments during infection. In environments with little to no glucose, non-fermentable compounds, such as acetate and ethanol, can be important sources of carbon. A requirement for the consumption of two-carbon compounds such as acetate is the existence of efficient transport systems. We have identified two acetate transporters Ady2 and Ato2 in C. neoformans. ADY2, ATO2, and ADY2/ATO2 gene knockout mutants had statistically significant reduced survival in the macrophage survival experiments in comparison to a wild type strain, suggesting an important role for the transporters in pathogenesis. This has been further substantiated by preliminary mouse studies in which the ADY2/ATO2 double knockout mutant has been shown to be completely avirulent. In addition to investigating acetate transport, we are using molecular approaches to investigate the role(s) of other acetate utilization proteins and enzymes in the pathogenesis of C. neoformans.
Matthew Turnbull, Department of Biological Sciences and Department of Environmental Sciences
Gap junctions are intercellular channels that occur in nearly all multicellular animal phyla, tissues and ontogenic and physiological activities involving cellular interactions. As such, they have been linked to numerous biomedical and fundamental biological processes. Surprisingly, given their near-omnipresence, the structures are comprised by convergently evolved multi-gene families known as Connexins and Pannexins. While Connexins are restricted to chordate animals, Pannexins occur in invertebrates as well as vertebrates. Better understanding of Pannexins in invertebrates both will shed light on the role of these proteins and gap junctions in chordates, as well as describe their contribution to insect physiology. The Turnbull lab is investigating the roles of insect Pannexins, known as Innexins, in regulation of insect immunity and other physiological systems. We also are investigating the biology of Innexin homologues isolated from a mutualistic insect virus transmitted by wasps that parasitize other insects; infection with this virus disrupts immunity and development of hosts, which are agricultural pests. Depending on student interests, opportunities exist to study physiological function and biochemistry of insect and virus Innexins in transgenic Drosophila melanogaster, cell culture models and in insect tissues. Techniques used will vary with project but include recombinant protein expression systems, immunomicroscopy, and bioassays such as immune challenges with live insects.
Jeremy Tzeng, Department of Biological Sciences
The long-term goal of my research is to develop prevention and therapeutic approaches to reduce, augment, enhance or replace the use of antibiotics. My approach to achieve the goal is to study the microbe and host interactions, as well as the mechanisms enabling the microorganisms to be resistant to the actions of antibiotics. Understanding of these interactions and resistance mechanisms will enable us to develop effective disease prevention and treatment methods. Under this vision, my research team has:
- Developed nanoparticles that display multivalent bacterial adhesin-specific receptors, mimicking host cell surface, to facilitate their bindings to targeted bacteria.
- Functionalized superparamagnetic iron-oxide nanoparticles with adhesin-specific receptors to study the feasibility of using such nanoparticles for inactivation of specific antibiotic-resistant bacteria.
- Developed adhesin-specific biosensors for rapid and sensitive detection of targeted pathogens.
- Developed antimicrobial peptides that are target-specific to control the growth of foodborne pathogens and to minimize the emergence of antibiotic resistant bacteria.
- Identified nutraceutical compounds that exhibit antimicrobial activities but with low host toxicities.
- Has identified bacterial efflux pump inhibitors from nutraceuticals to facilitate the effective treatment of multi-drug-resistant pathogens.
- Developed modified surfaces, e.g., catheters, surgical pins and plates, that prevent bacterial attachment (biofilm formation).
Christina Wells, Department of Biological Sciences
Project: Reniform nematode co-option of host plant genes.
Parasitic worms secrete proteins that alter gene expression in plant roots, leading to the formation of specialized feeding structures called syncytia. Our lab has recently assembled detailed transcriptomic time courses of host plant gene expression during syncytial development in cotton and soybean. We are investigating individual candidate genes using plants in which the genes of interest have been knocked out (tDNA insertional mutants). The REU student will investigate a single insertional line to validate the mutation and characterize worm reproduction on mutant and wild-type plants. During the project, the student will learn basic molecular biology and microscopy techniques and will develop skills in data analysis and presentation. The student will participate in weekly lab meetings and paper discussions, and will have the opportunity to contribute to relevant lab publications. The Wells lab has a strong track record of mentoring over 20 high school and undergraduate students, several of whom have co-authored peer-reviewed journal articles.