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. |
Polymeric Materials for Controlled Release of NO with Zero Order Profiles This technology offers a means for chemically synthesizing NO time releasing polymers that are insoluble in water. The technology was developed as a means to control the release of NO over a period of thirty days. Evidence of NO release observed in early experiments suggests first order kinetics. Additionally, this synthetic route offers a means for synthesizing new NO releasing polymers that achieve greater efficiency through removal of the BOC protection/ deprotection steps in traditional methods for producing NO releasing compounds. |
Methods of Dendritic Drugs for Controlled Release in Drug Delivery This technology enables a novel drug delivery method that utilizes dendrimers as a quantitative and controlled mechanism of delivery; biocompatible linkers with biodegradable bonding allow drug molecules to be incorporated into a dendritic structure to form a dendritic drug that consists of a known amount of drug molecules. Each layer of the cascade structure of the dendrimer is designed to contain a known amount of drug, with the largest amount at the periphery and the lowest amount at the core. The dendrimer delivery platform appears to be very flexible with application for many classes of drugs including anti-fungals, anti-inflammatory agents, anticancer drugs and anti-bacterials. The platform could be designed for diverse administration paths: oral, rectal, or parenteral, intravenous, intramuscular, intraperitoneal, intraspinal, intracranial, topical, ocular, and subcutaneous routes. |
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. |
PiezoBiosensor for Detecting Complex Environmental and Chemical Agents This technology is an apparatus with multiple piezoelectric mass sensors for use in immunochemical detection of diagnostically relevant analytes. The detection is in real time, and each piezoelectric mass sensor comprises a piezoelectric crystal with a receptor surface containing recombinant antibodies that are specific for a particular antigen. The technology measures the binding of antigens to the recombinant antibodies by tracking a change in mass on the receptor surface which is detected as a change in resonant frequency. This technology emerged from a research program oriented toward developing piezobiosensors and electrochemical sensors for detection in complex environmental and clinical samples. The research program is focused on combining the excellent sensitivity of electrochemical and mass sensing with the superb selectivity of biological recognition processes (e.g., protein-protein interactions, DNA-protein interactions, carbohydrate-protein interactions). |
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. |
Biomedical Research Support Facility/Laboratory Animal Management Services This facility provides education and training in laboratory animal science, and provides services such as the procurement, housing and care of animals. The facility is focused on animal health and the monitoring of regulatory compliance with university, Public Health Service and United States Department of Agriculture standards. The facility provides a centralized space for research involving any vertebrate animals. The facility is classified as a P3 facility which is suitable for work with infectious agents, which may cause serious or potentially lethal diseases as a result of exposure by the inhalation route. The facility has excess capacity and is seeking to fill that capacity. |
Amphiphilic Silver Delivery of Bactericidal Delivery in Coatings  This technology is a method for embedding metals (specifically, silver) into coatings and textiles across a variety of applications. Silver has a variety of uses in pharmaceuticals and has found increasing application as a bactericide and in treatments for conditions ranging from severe burns to Legionnaires Disease. This technology enables textile coatings incorporating the bactericidal properties of silver into diverse range of products such as catheters, stents, implants, hospital garments, free flow filters, mattress covers, carpeting and air filters. |
Chiral Ligands For Enantioselective Catalysis  MTU researchers have developed new types of catalysts for enantioselective reactions. These catalysts are all based on several novel common planar chiral benzoferrocene precursors. They are easy to synthesize and have high enantioselectivity for a wide range of reactions such as asymmetric Heck reactions, palladium catalyzed asymmetric allylic alkylation (AAA) reactions, and catalytic asymmetric Diels-Alder reactions. All these reactions are important both in academic research and to the pharmaceutical industry providing cheaper medicines and significantly impacting the advancement of medical science.
Many therapeutic agents used for treating human diseases function through binding to biomolecules such as proteins and nucleic acids. Because these biomolecules are asymmetric, they can differentiate the chirality of medicines. Usually, one enantiomer of a medicinal molecule has a therapeutic effect, while the other enantiomer does not and may even have adverse effects. Consequently, the development of methodologies that can produce enantiomerically pure medicines is highly desired. Of the various methods to achieve this goal, catalytic enantioselective synthesis is the most attractive, because a relatively small amount of optically pure molecules (catalysts, which are usually expensive) can produce a large amount of enantiomerically pure or enriched products. One of the crucial requirements for this method to succeed is to design the structure of the catalyst so that it can most effectively transfer its chirality to the product. Thousands of catalysts have been synthesized, and some of them have found important applications in the pharmaceutical industry and academic health-related research. |
Purification of synthetic oligonucleotides Two highly efficient, low cost methods for large scale purification of synthetic oligonucleotides have been developed through a researcher at Michigan Tech. Synthetic oligonucleotides have found wide applications in biology and medicine. With two oligonucleotide drugs on the market and more than 40 others in various stages of clinical trial, the interest in using oligonucleotides as therapeutic agents continues to grow. Consequently, the development of highly efficient and low cost methods for large scale production of oligonucleotides is desired. One of the obstacles to achieving this goal is the efficient removal of the failure sequences generated in the synthesis from the desired full length sequences. Currently used methods include gel electrophoresis, HPLC and others – all of which are high cost, require much labor and are not suitable for large scale purification. |
A mechanically stimulating tissue engineering bioreactor Dr. Seth Donahue in Michigan Tech's Biomedical Engineering Department has studied tissue engineering for several years and has developed a new mechanically stimulating tissue bioreactor that has advantages over current methods of tissue engineering. The bioreactor allows fluid from two different pumps to flow through the chamber that hold the cell assemblies and a 3 dimensional scaffold material. One pump provides fluid with nutrients to the cells in the chamber and another pump produces an oscillatory flow that mechanically stimulates the cells. Studies conducted by Dr. Donahue have shown that cells grown in a 3-dimensional culture have different characteristics than cells grown in a traditional 2-dimensional culture and that the oscillatory or pulsatile flow of the reactor is advantageous to desirable tissue growth and tissue properties.
Cell and tissue graft therapy is currently used to treat many clinical disorders such as trauma and cancer. Obtaining tissue for these grafts is commonly done through allografting or autografting. Allografting involves transplanting tissue from either a tissue donor and carries risk of disease transmission or transplant failure due to immune response. Allografts are also susceptible to fracture or non-union. Autografting involves transplanting tissue from one part of a patient's body to another and requires additional surgery to obtain the tissue which can lead to donor site morbidity and pain to the patient. As a result of potential complications related to allografting and autografting procedures, and the limited availability of tissue methods for engineering tissues by growing them in artificial medium to later be implanted by, surgical procedure have been developed. |
Analysis and Annotation Tool (AAT) Most small engines still use traditional carburetor technology which produces decreased reliability and increased emissions when compared to fuel injection. Current electronic fuel injection technology is not cost effective for application in small engines. This technology allows for the manufacture of a low-cost mechanical fuel injector that can be utilized in place of a traditional carburetor. Development work to-date suggests that the mechanical injector can be designed to simply replace existing carburetors on production small engines without any significant redesign other than a means to connect the injector to the engine’s camshaft. |
MAP: A Multiple Alignment Program The MAP program computes a multiple global alignment of sequences using iterative pairwise method. The underlying algorithm for aligning two sequences computes a best overlapping alignment between two sequences without penalizing terminal gaps. In addition, long internal gaps in short sequences are not heavily penalized. So MAP is good at producing an alignment where there are long terminal or internal gaps in some sequences. The MAP program is designed in a space-efficient manner so long sequences can be aligned. Note that sequences must be all DNA/cDNA sequences or all protein sequences. |
MEMS Center in Wireless Integrated Microsystems A multi-university National Engineering Research Center in Wireless Integrated Microsystems funded by the National Science Foundation gives MTU a strong base for microtechnology research. Among its first projects, the center will design a next generation cochlear implant for which MTU will design and build a |
Coatings for Carbon Nanotubes Research allows attachment of polymers to carbon nanotubes in a manner that preserves their conductivity and strength while permitting the nanotubes to support sensors. Functional conjugated polymers are designed and synthesized to modify carbon nanotube electrodes via strong pi-pi stacking interaction between the polymers and the nanotubes. Artificial and biological receptors, such as enzyme, antibody, and single strand DNA can be incorporated into the synthetic functional conjugated polymers. Electrochemistry [labeled biosensors] is employed to detect chemical or biological recognition. |
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. |
Biological Processes that Involve Nucleic Acids The primary focus of the research is the investigation of nucleic acid damage processes utilizing the independent generation of reactive intermediates in nucleosides and nucleotides. Investigations center around the generation of a variety of C-3'-nucleoside radicals and the elucidation of the fate of these species. To facilitate the independent generation of radical intermediates in these biological systems a variety of modified nucleic acids are required which have the ability to function as radical precursors. These modified derivatives can be synthesized using modern synthetic organic techniques and incorporated into DNA and RNA either chemically or enzymatically. By elucidating the mechanisms and consequently the fate of these species several questions can be addressed concerning the role of nucleic acid damaging agents in the development of disease and the aging process. |
chemistry of free radical Species Produced by the Irradiation of Biomolecules Of principal interest are the mechanisms for radiation damage to DNA. The principal biological effect of radiation on a cell is caused by the direct interaction of radiation with DNA or molecules immediately surrounding the DNA which transmit the radiation damage to the DNA. Professor Sevilla's lab has established that the initial effect of radiation is to produce ion radicals on the DNA bases and recently has found DNA radicals on the sugar phosphate backbone. These species directly lead to strand breaks and biologically relevant damage.
Recent efforts have looked into the production of sugar radicals in DNA by high energy irradiation. These species are of critical importance to the subsequent biological damage and as a consequence quantitation of the numbers of sugar radicals and their identity gives important mechanistic information. Work in this lab has found that about 10% of all radicals produced are on the sugar phosphate backbone for gamma rays but as much as 30% of radicals are on the sugar phosphate backbone for ion beam irradiated DNA. This lead to the hypothesis that excited states of the DNA base cation radicals may lead to damage to the sugar portion of DNA. A series of recent papers from this lab has shown this is indeed the case. These efforts have identified the C1’, C3’ and C5’ sites on the sugar as those that are most prone to damage by this mechanism. |
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. |
Biointerfaces/Bioadhesion for Characterization and Modification of Implant Surfaces Metals and alloys, such as titanium and stainless steel, rely on the presence of an oxide film to act as a barrier preventing further oxidation in active environments, such as the human body. It is also the oxide film that forms the interface between the biomaterial and the body, with which cells and proteins interact. Oxide films vary in properties, depending in part on the method by which they are formed and the environment in which they are placed. These and other factors dictate the properties of the film such as thickness, roughness, composition, heterogeneity, electronic properties, and wettability, all of which play a role in cell interaction. This program of research is directed toward understanding the effect of surface properties of biomaterials on their biocompatibility. Students also chemically modify the surfaces of implant materials to improve osteoblast adhesion and differentiation. For example, a novel technology for formation and growth of bone-like apatite coatings on implants has been developed and then used in testing osteoblast cell activity on fabricated implant-apatite composites. |
Structural Roles of Water in Bone Observed by Solid-State NMR Vibrational spectroscopy is used to solve problems dealing with molecular structure. Nearly any type of sample can be analyzed by Raman spectroscopy because of the flexibility of using a focused laser beam as the light source. The current focus is on apatite, a form of calcium phosphate, which is the major constituent of bone and is also found as a natural mineral in rocks. The lab creates apatite substituted with ions typically found in bone in order to support Raman analysis of bone tissue. A silane hydrolysis process also is being explored, to develop a Raman detection method and study the kinetics of the process. The materials studied are diverse and have also included proteins containing the heme group (hemoglobin and cytochrome oxidase), inorganic glasses (germanium diselenide doped with metals) and polymers (azoazromatic polyethers). Modern computational modeling of molecular structure and conformation augments experimental studies. |
Stem Cell Research for Neurodegenerative Diseases Research interests are in the area of behavioral neuroscience. A recent focus has been on stem cell and pharmacological treatments for brain damage and neurodegenerative diseases such as Huntington’s, Parkinson’s and Alzheimer’s diseases. |
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. |
Biomaterials synthesis with medical applications Hydrophilic polymers, specifically polysaccharides, are being examined because of their non-adhesive properties. These polymers are synthesized via enzymatic polymerization without toxic solvents or chemicals. Polysaccharide-based materials are used for the development of an improved, artificial, biodegradable skin scaffold for burn victims. Also in development is an anti-thrombogenic coating for artificial heart valves. The coating is being enzymatically synthesized under non-toxic conditions with various copolymers and polymer structures being tested. |
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. |
Aquatic Ecological Tools for Great Lakes Survival Research focus is on the decline of the yellow perch population in Lake Michigan. Areas of expertise include fresh water food webs, zooplankton ecology, aquatic biodiversity and larval fish recruitment. Also responsible for directing the Michigan Water Research Center, a collaboration of researchers who evaluate surface water in lakes, streams and wetlands. The Center addresses such local concerns as nuisance algae, bacteria, contaminants, drinking water safety and recreational water degradation. Researchers in the center work as a team to assess lake nutrients and acidity, test for toxins and evaluate fish populations. |
Environmental Microbiology Research An ABI 310 automated DNA sequencer and a Biolog microbial identification system improves the capacity for environmental microbiology research in Central Michigan. While the primary use of this equipment will be for environmental microbiology research at CMA and Alma College, a secondary but equally important use of this equipment will be for research and teaching by additional CMU Biology faculty. The equipment will meet the needs of a growing number of researchers utilizing molecular techniques. Further, the instruments will be integrated into a number of courses that will reach students at a wide range of levels in their academic preparation. Through additional programs, including the Ronald E. McNair Post Baccalaureate Achievement Program, students underrepresented in the sciences will continue to be encouraged to participate in research projects utilizing the requested instrumentation. |
An Investigation of the Mechanism Producing Rhythmic Beating in Cilia and Flagella Flagella and cilia are self-contained biological machines (micro in scale in the aggregate but consisting of nanoscale mechanical parts) that convert chemical energy from ATP into useful mechanical work. These are highly conserved eukaryotic organelles that are found in plants, protistans, and animals (including humans). The general function of flagella and cilia is nearly always to move in a rhythmic fashion (although the nonmotile "sensory cilia" represent a notable exception). These rhythmic movements play important roles in various life processes such as reproduction, embryonic development, and movement of fluids across cell surfaces in contexts as varied as protozoan feeding and mucus clearing in the trachea and bronchi of lungs. We still do not fully understand how this basic component of a living eukaryotic cell works. This project is directed at understanding, at a precise molecular and physical level, how cilia and flagella work. The major goal is to experimentally gather critical physical information about the flagellum and to incorporate it into a theoretical and computational model of flagellar mechanics. To accomplish this goal, Dr. Lindemann has developed a unique set of tools that will aid him in this endeavor. One such tool is a novel method, based on force-calibrated glass microprobes, for measuring small forces, which enables the measurement of force actively produced by flagella and the passive mechanical stiffness of a flagellum. This novel methodology permits the acquisition of new and useful information that can be used to describe the mechanical behavior of flagella. Another tool is a detailed computational model of the mechanics of the axoneme (the mechanostructural component of the flagellum or cilium) that Dr. Lindemann has developed, termed The Geometric Clutch model. This simulation model has successfully duplicated, and even predicted, the behavior of cilia and flagella. The computer model provides a framework that can be used to build toward a more complete picture of the mechanics of the axoneme. Dr. Lindemann will use the data from his force measurement experiments to improve the computer model. When experimental results and computed simulation are in agreement, the model often provides a means to understand the mechanism behind the observed result; in other words, the combination of experimentation and modelling can help us learn how the flagellum works.
The goal of the project is to understand how flagella and cilia work. Therefore, the project will contribute basic scientific knowledge about the living eukaryotic cell. There are very few research programs that are combining computer modeling with laboratory experiments to study the mechanical workings of flagella. The mechanical and physical information obtained from these studies complement the remarkable advances in understanding the flagellum at the molecular level. The Geometric Clutch model allows the physical properties of many specific axoneme structures to be identified with the appropriate molecular components. This has already yielded concrete predictions about properties that the various molecular components, including spokes, the dynein heads and the nexin links, must have in order to be functional in a flagellum. Dr. Lindemann's research program has a well-established base of experience with mammalian sperm. He is now developing a computer model specific to the mouse sperm flagellum. The mouse is one of the primary research model systems and, as such, a large data base is available on the genome and molecular biology of this animal. A working model of the mouse sperm axoneme will position Dr. Lindemann's laboratory as the only research program that can do experimental measurements on mouse sperm and also examine the results in a theoretical framework. Dr. Lindemann is also embarking on a collaboration with Dr. David Mitchell that will involve the analysis of Dr. Mitchell's remarkable transmission electron micrographs of Chlamydomonas flagella, obtained by Dr. Mitchell through the use of his innovative methods of rapid fixation and orientation of samples for sectioning. Again, the large data base of molecular and genetic information about the structure and properties of the flagella of this model unicellular organism will assist in the analysis and interpretation of the images in terms of mechanism.
Dr. Lindemann's work applies physics and computational modeling to a biological system. It has drawn the interest of people in the mathematics, physics and engineering communities because it is a successful melding of ideas from different disciplines. The flagellum is nature's own micro-machine, built of nanoscale parts. Despite the extensive knowledge of the biochemistry of the flagellum that is available, it is only by understanding the mechanical properties that we can reach a full understanding of how it works. This understanding is crucial to the development of biomimetic devices that harness molecular motors to create new functional and useful nano- and micro-machines. We must observe and learn from nature to build tomorrow's nanotechnology. Dr. Lindemann has an extensive record of mentoring undergraduate students and introducing them to the principles and practice of laboratory research, and many of the undergraduates are co-authors on scientific reports and upon graduation, advance into careers in science, teaching and medicine. This project will continue to be a vehicle for this integration of research with teaching and training. |
Biochemical Characterization of Carbofuran Hydroxylase This project supports collaborative research between Dr. Rasul Chaudhry, Department of Biological Sciences, Oakland University, Oakland, Michigan and Dr. Narayan Roy, Department of Biochemistry and Molecular Biology, University of Rajshahi, Bangladesh. They plan to study certain enzymes that degrade pesticides. The PIs have studied microbial degradation of carbamates and isolated microorganisms that can degrade these chemicals. Microorganisms either hydrolyze or oxidize the chemicals. Hydrolytic processes are less efficient and partially degrade pesticides, whereas oxidation reactions involved in degradation of carbamates are efficient, but more complex. The goal of the study is to determine the molecular mechanism of microbial oxidation of carbofuran. Using a variety of biochemical and molecular biology techniques, the PIs will test the following hypotheses: 1. A mixed function oxygenase, carbofuran hydroxylase, catalyzes the reaction of carbofuran to 4-hydroxycarbofuran. 2. A cytochrome P-450 or another unknown cofactor is involved in the electron transport circuit from NADPH to molecular oxygen. The following four specific aims will be pursued: 1. Purify the enzyme complex responsible for hydroxylation of carbofuran, 2. Characterize the purified enzyme, 3. Determine the components of the hydroxylase and their interactions responsible for catalyzing the reaction, and 4. Investigate the diversity of pesticide-degrading microorganisms. A combined expertise of the collaborating investigators, a biochemist and a molecular biologist will help solve the novel mechanism of induction and functioning of the hydroxylase complex that is key to the effective inactivation of carbofuran in the environment.
Pesticides such as carbofuran are the major group of chemicals that are used in large amounts for improving productivity and quality of crops. While these chemicals are vital to agriculture, human exposure to these pesticides through consumption of foods or drinking water has been suggested to play a key role in the early onset of neurological diseases, old age diseases such as Alzheimer's disease, immunological and reproductive disorders as well as an increase in the risk of non-Hodgkin lymphoma. This study will substantiate and extend our understanding of microbial metabolic diversity. It will also help develop new strategies for their safe and effective use as well as disposal. |
A Student-Accessible Model for Human Genetics Using Fast Plants and Microsatellite Markers An experimental system that models human genetics is being developed for instructional laboratories. The experiments involve microsatellite markers in rapid cycling Brassica rapa (RCBr), or Fast Plants. The objectives of the project include development of microsatellite markers for RCBr and analysis methods that make them accessible to the instructional lab, strains of RCBr with defined microsatellite genotypes resembling human genetic variation, a pedigree analysis experiment for linkage analysis with microsatellite markers and the model genetic disease anthocyaninless, a virtual laboratory in which students will exchange data with peers, analyze data, and allow the instructor to track their data analysis, and a prototype web site and manual for high school teachers and students to analyze data generated by the college labs.
The types of genetic analysis the students can use in these instructional labs include techniques of microsatellite analysis, assessment of informativeness of families, inheritance of highly polymorphic markers, and haplotype analysis. Since genetic linkage cannot be established from a single family, students use the virtual lab to pool data. In this way, students can perform experiments that accurately model human genetic analysis and gain experience with molecular markers. The web-based system facilitates analysis of complex data, pooling of individual student data, and instructor tracking of analysis. |
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. |
C-3'-Nucleic Acid Radicals: Generation and Mechanistic Investigations Oxidative processes are at the heart of numerous chemical and biochemical processes, including the damage of nucleic acids by ionizing radiation or specific drug interactions. This project involves the synthesis of modified nucleosides and nucleotides that will permit the elucidation of the mechanism of degradation of C-3' nucleotide radicals in DNA and RNA. Modifed nucleosides containing photoactive functional groups will be synthesized and incorporated into small DNAs and RNAs designed for the investigation of damage events. The nature and fate of nucleoside radicals derived from these site-specifically functionalized nucleic acid systems will be explored by a variety of chemical, analytical, and biophysical methods. A curriculum for a Master of Science degree will be developed, targeting specific groups in an effort to increase the pool of underrepresented minorities in the chemical workforce. This program specifically targets students who are ill prepared for graduate studies or who have not been successful in previous attempts to receive a graduate degree due to a lack of proper preparation.
Professor Amanda Bryant-Friedrich, of the Department of Chemistry at Oakland University, is developing an understanding of the chemical processes which result in the damage of DNA and RNA. Radiation, drug interactions, and other oxidative processes can lead to the formation of nucleic acid radicals. Through the synthesis and manipulation of modified nucleic acid subunits, Professor Bryant-Friedrich is elucidating the mechanisms by which these radicals lead to nucleic acid degradation. Professor Bryant-Friedrich is also working toward increasing the representation of women and minorities in the chemical workforce. Through development of a Master of Science program at Oakland University, Professor Bryant-Friedrich will provide a program targeting students who are academically ill-prepared for graduate study, placing them on track for employment or for placement in competitive doctoral programs. |
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