Conjugate Addition Products of Primary Amines and Activated Acceptors  This technology is based on an organic synthesis method of reacting amines with alpha, beta unsaturated compounds to produce dendrimer structures. The overall reaction mechanism produces Michael addition products that include double Michael additions and vicarious Michael additions. The potential for this synthetic process lies in its flexibility to introduce new geometric/amplification, structural parameters into the core, and interior or terminal components of a dendrimer architecture. Importantly, this allows for the design or creation of new tunable dendritic properties. |
Molecules That May Have Biological Significance  This research program focuses the development of analogs of natural products, with specific emphasis on synthesizing complexes of nucleosides and nucleotides. In addition, the research probes electronic properties of molecules through the use of perflouroalkyl groups and chain length modifications for potential exploration of the biological properties of these molecules. The program is directed toward synthesizing materials that exhibit antiviral, anticancer, antisense properties and serve as bio-probes, as well as the development of new synthetic methodologies. |
Center for Biomedical Research This center supports state-of-the-art research facilities for biomedical research, promotes and publicizes biomedical research, and aggressively encourages and supports initiatives for support of biomedical research. The center sponsors research presentations and colloquia, provides funds to support pilot research projects, and identifies novel funding. In addition, the center assists with the development and submission of proposals for external funding of major multi-investigator equipment, (b) provides and maintains readily accessible multi-user equipment facilities, and (c) facilitates access to specialized facilities and services. In addition to supporting and promoting collaborations among its members, the center facilitates interactions between members and other institutions, including pharmaceutical and biotechnology companies, and promotes access to biomedical research equipment within the center. |
Two Dimensional Gas Chromatography Instrument At the heart of the technology for gas chromatography (GC) is a valve that accumulates a sample from a primary column for transfer to a secondary column in parallel. The primary column has a smaller fluid flow capacity than the combined fluid capacities of the secondary columns. In this manner, the chromatographic separations of the primary and secondary columns are matched to provide the best available separation of compounds in the sample. This technology relates to gas chromatography in that it provides a method and means to separate VOC’s faster and, more accurately, and potentially cheaper than traditional GC does. As an example, this novel multidimensional gas chromatography system can separate and quantify over one hundred compounds in less than ten minutes. A prototype exists and development of this technology continues through a series of projects that include establishing a retention time database of a wide variety of VOCs, writing improved software for instrument operation and data analysis, and developing theoretical methods to predict retention times from compound structures. |
Coatings Research Institute  The CRI's two-fold mission is to be a leading academic organization that develops relevant scientific knowledge for understanding and for expanding the science and technology of paints, coatings, inks, adhesives and related nano-based materials. Areas of expertise represented in the CRI include, among others, coating technologies and formulation, polymer modification, cross-linking mechanisms and enabling technologies such as nanotechnology (nanoparticle materials), polymer structure/property relationships, characterization, vibrational spectroscopy (Raman and FT-IR), thermal analysis (DSC,DMA,TGA, DEA) and nanotribology. |
National Dendrimer and Nanotechnology Center The National Dendrimer and Nanotechnology Center is the catalyst for dendrimer-based research initiatives. The Center’s current research agenda focuses on several types of dendrimer and nanoscale sciences: Drug encapsulation, release and disease targeting protocols are being established and tested for cancer therapy and anti-flammatory drug systems using a range of dendrimer carrier structures; researching cytotoxicity of dendrimers and other nanoscale structures; the use of dendrimers as a catalyst in the production of carbon nanotubes at the lowest temperatures recorded; the attachment of oligonucleotides to dendrimers for targeting, amplification or detection in biological systems; development of nuclear magnetic reagents which allow higher resolution and site specific targeting to disease or inflammation; stabilization of nano-crystals or quantum dots with unique optical, electronic or other properties for use in bio-labeling, and flat panel display technologies; development of lower-cost synthetic routes to new proprietary dendrimers and dendritic polymers; development of dendrimers as in-vivo nano-diagnostic agents and devices. |
Development of Green Organic Catalysts This research program is focused on development of green organic catalysts based on an architecture of buckminsterfullerene (C60) molecules surrounding either a polymer resin bead or dendrimer. These catalysts are activated by light and can function in either organic or aqueous media. We hope to further develop the catalysts to the point where we can carry out stereoselective oxidations and/or decontaminate water. |
Linoleic Acid This research is focused on two components. First, the metabolic disposition and biological activity of oxidized derivatives of linoleic acid is being actively investigated. The major pathway for oxygenation of linoleic acid involves production of 13-hydroperoxyoctadecadienoic acid by the action of lipoxygenases or cyclooxygenases. This is followed by reduction of the hydroperoxy fatty acid to the hydroxy derivative (13-HODE) and the subsequent dehydrogenation of 13-HODE to the 2,4-dienone 13-OXO. Research efforts are currently focused in two areas related to this metabolic pathway. One area of emphasis involves unraveling the biochemical contribution of 13-HODE dehydrogenase to cellular regulation. A second area of interest involves identification of crucial cellular targets interacting with key metabolites of oxidized linoleic acid. Both chemical and biochemical techniques are employed to address these questions and elucidate these pathways.
A second major area of interest involves attempts to elucidate the mechanism by which conjugated derivatives of linoleic acid, known as CLAs, inhibit mammary tumorigenesis. The CLAs have been shown to be non-toxic inhibitors of both initiation and post initiation events during mammary carcinogenesis. The emphasis in these investigations involves an examination of the potential modulation of the oxidative metabolism of polyunsaturated fatty acids by CLA. Again, identification of biological targets and the elucidation of metabolic pathways available to CLA are major goals of these NIH-supported investigations. |
Bidomain Model for Predicting the Strength-interval Curve of Cardiac Tissue The bidomain model consists of two coupled, nonlinear partial differential equations used in this research program to simulate cardiac bioelectrical phenomena. Data revealed that the predicted the shape of the strength-interval curve using the bidomain model conformed to experimental observations. Applications in a number of domains, included investigational, experimental and clinical uses, can be anticipated. |
Ionic Liquid Chemical Sensing Devices This technology emerged from a long-term effort devoted to developing piezobiosensors and electrochemical sensors for detection in complex environments. The technology is designed to detect chemicals using novel ionic liquid technology. Critical features of the technology include: (1) methods to immobilize ionic liquids on solid supports, (2) capabilities for characterizing and elucidating the physicochemical properties of immobilized ionic liquids, (3) new ionic liquids incorporating functional groups capable of acting as anchors or tags for surface immobilization, and (4) ionic liquid thin films for array-based gas sensing and high-temperature gas sensing. |
Probing the Structure and Functional Importance of Arginase This program of research focuses on structure-function-activity relationships for enzymes involved in arginine metabolism. Arginase is a manganoprotein that catalyzes the hydrolysis of L-arginine to form L-ornithine and urea. Rat liver (cytosolic) and human kidney (mitochondrial) isozymes have been expressed in and purified from E. coli. Crystal structures for both isozymes have been determined. Inhibitor studies have shown that extra-hepatic arginases play a role in regulating nitric oxide production in both male and female sexual organs. Current studies focus on the role of individual amino acids in the catalytic cycle as probed by site-directed mutagenesis. |
Motor response treatment in primates with Parkinson’s disease Principal research interests focus on the treatment of Parkinson’s disease and other neurodegenerative disorders. The major goal of the laboratory is to uncover the underlying molecular genetic, biochemical, and psychobiological abnormalities that produce clinical symptoms in neurodegenerative diseases such as Parkinson’s, Alzheimer’s and Huntington’s. The current emphasis is on interactions of dopamine and glutamate in regulating basal ganglia output neurons because of the relevance of these tramsmitters to the pathophysiology and treatment of neurodegenerative disease. Current projects include investigations of the pathogenesis of motor response complications associated with chronic levodopa therapy in Parkinson’s disease. |
Examining Biomass Substrates in Ethanol Production as Source of Alternative Fuel Bio-fuel ethanol as an alternative fuel is gaining interests for environmental and economical reasons. To reach ethanol goals needed in the United States, it will be essential to take advantage of various biomass substrates for ethanol production (e.g. agricultural and industrial waste products). Recent work includes study of the growth inhibitor, furfural, which induces cellular stress signals in Saccharomyces cerevisiae. Using various fluorescent indicators and transmission electron microscopy techniques, it was determined that furfural causes an increase in reactive oxygen species accumulation, cellular membrane damage (vacuole and mitochondrial membranes), chromatin damage, and cytoskeletal damage in wild-type S. cerevisiae. Whether or not overexpressing any of the previously identified genes will reduce oxidative damage is being investigated. |
Behavioral Neuroscience Applications for Disease Treatment Research focus is in the area of behavioral neuroscience. Experiments explore mechanisms that underlie plasticity and recovery of the mammalian brain following neuronal deterioration-induced deficits that disrupt behavior. The team targets Parkinson’s disease, exploring age-dependent plasticity of the basal ganglia dopamine system, using an animal model. Research also is focused on neurochemical control mechanisms within transgenic mice that model Huntington’s disease, specifically those mechanisms involved in natural behavioral activation. Techniques include in-vivo microdialysis, single unit electrophysiology, and iontophoresis experiments using awake and unrestrained animals, and immunohistochemistry. |
Involvement of p59fyn in XEphA4 signaling Eph class receptors are cell surface proteins that, when activated by their ligands, cause cell-cell repulsion, which is used to limit cellular interactions, thus aiding in a variety of processes, such as tissue formation and guidance of migrating cells. Activation of one member of this family in Xenopus laevis, XEphA4, leads to reorganization of the actin cytoskeleton via a mechanism involving inhibition of the small GTPase XRhoA. The rest of the biochemical pathway by which XEphA4 mediates its effects is largely unknown. This project will test the hypothesis that the tyrosine kinase Fyn (a member of the Src family of non-receptor tyrosine kinases) is involved in signaling by XEphA4. The hypothesis will be tested using a Xenopus laevis embryo assay system. This system allows expression and activation of XEphA4 in early frog embryos (at a time when the receptor would not normally be expressed), which results in loss of cell adhesion, change in cell shape, and loss of cell polarity by epithelial cells. Candidate molecules in the signaling pathway, such as Fyn in the current project, can be tested by expressing mutant forms of the candidate molecule alone or in conjunction with XEphA4 and assessing the effect on embryo phenotype. The hypothesis will be tested using experimental approaches that comprise four objectives, each of which tests a prediction based on the hypothesis. Objective 1 will test whether constitutively-active Fyn can recreate the XEphA4 phenotype. Objective 2 will determine whether inhibition of Fyn prevents the phenotypic effects of XEphA4. Objective 3 will test whether constitutive activity of XRhoA can prevent the effects of active Fyn. Objective 4 will assay for changes in Fyn activity levels in response to XEPhA4 activity. This project should add greatly to understanding of Eph receptor signaling, and will have broader impact through training of graduate and undergraduate students, including pre-service secondary-level biology teachers, and through outreach programs to local secondary schools. |
Rhizosphere Influence on Hydrocarbon Metabolizing Microorganisms The goal of this project is to use cultivation and non-cultivation based methods to characterize the microbial populations associated with plant rhizospheres in hydrocarbon-impacted soils. A series of plots have been established in polynuclear aromatic hydrocarbon (PAH) impacted soils that have been planted with species native to Michigan. Preliminary results with these plots indicate that individual plant species have different effects on the extent of hydrocarbon removal. In this research project, experiments will be conducted to evaluate the different influences that unique plant species have on the microbial communities inhabiting the rhizospheres. This will be performed by analyzing soil samples collected from different plots at various time intervals. Microbial communities will be characterized by 1) sequencing a gene that will enable the identification of microorganisms present (16S rRNA genes) 2) sequencing genes involved in PAH-degradation (PAH dioxygenases), and 3) comparing carbon utilization profiles of rhizosphere samples. It is anticipated that these experiments will reveal microbiological factors that enable some plants to accelerate the removal of PAHs from contaminated soils, whereas others hinder their removal. The broader impacts include developing an ecological framework for understanding how an applied technology like phytoremediation can be optimized. Some aspects of this project will also be integrated into a semester long cooperative laboratory experience for a microbial ecology and plant physiology class taught during the same semester. Further, this support will be used to increase research opportunities for underrepresented populations through local outreach and through additional, formal NSF channels (e.g. REU and RET supplements). |
Regulation of 5-Aminolevulinic Acid Biosynthesis In Rhodobacter Sphaeroides 2.4.1 As the common precursor to all tetrapyrroles, important biomolecules that include hemes, (bacterio)chlorophyll, and vitamin B12, 5-aminolevulinic acid (ALA) formation is crucial to both energy metabolism and other biosynthetic processes. This project focuses on an investigation of the regulated synthesis of this essential compound in the metabolically versatile bacterium, Rhodobacter sphaeroides 2.4.1. The metabolic flexibility of this organism is made possible by its ability to form all of these tetrapyrroles; aerobic and anaerobic respiratory chains require heme-containing cytochromes, the photosynthetic apparatus requires bacteriochlorophyll, and key biosynthesis enzymes require the cofactor vitamin B12 for functionality. To accommodate the exceedingly variable need in both types and quantities of tetrapyrroles in these cells, ALA formation in R. sphaeroides is responsive to changes in many environmental parameters, including oxygen availability, incident light intensity, carbon source, nitrogen source, and iron availability. This responsiveness in ALA synthesis is due to the highly regulated expression of hemA, which encodes ALA synthase, the enzyme that catalyzes ALA formation in this organism. Thus, the hemA gene constitutes a powerful system for examining how cells integrate complex regulatory networks in R. sphaeroides 2.4.1. Sequence elements within the hemA gene that are necessary for its regulated expression have been identified. Other sequences that are not part of the hemA gene, but which affect its expression, have also been discovered. These sequences will be investigated in more detail to determine how the cell achieves the optimum expression of hemA, such that the total ALA requirement for all the various tetrapyrroles, in all their various concentrations, is met.
Because ALA is the necessary ingredient for the formation of molecules that are indispensable to the cell, understanding how its formation is regulated is of broad significance. In R. sphaeroides, as in animal cells, ALA is formed by the enzyme ALA synthase. Thus, R. sphaeroides is a prokaryotic paradigm of this critical biosynthetic reaction. The highly regulated hemA gene, coding for ALA synthase, constitutes an appropriate and amenable model to address questions of how cells can process multiple regulatory signals, since this gene is designed to respond appropriately to changing needs for ALA. |
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