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. |
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. |
PCAP- Parallel Contig Assembly Program (formerly CAP3 - Method for solving repeating problems with constraints)  The PCAP whole-genome assembly program, developed at Michigan Tech, can process tens of millions of reads into long sequences. The PCAP package is a set of programs for generating a genome assembly from a set of reads and a set of forward-reverse read pairs. PCAP can handle a genome of 30 Mb on a computer with one processor, a genome of 300 Mb on a shared-memory computer with 10 processors, and a genome of 3 Gb on a distributed computer cluster of 100 processors. The program has several features to address issues in whole-genome assembly increasing efficiency and accuracy. Test results completed on a mouse whole-genome data set of 30 million reads, show that the assembly computation was efficient enough to handle a whole-genome data set. Accuracy tests performed on a human chromosome 20 data set of 1.7 million reads indicated acceptable accuracy rates.
PCAP contains a few major programs for generating an assembly and a few minor programs for formatting an assembly and collecting statistics on an assembly. In addition, PCAP contains several Perl Scripts for automatically running the major and minor programs in the proper order. PCAP produces a contiguous assembly with a low global misassembly rate and is efficient in computer memory. An assembly in .ace file format produced by PCAP can be viewed and edited in Consed. |
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. |
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. |
Applied Mathematics Function to Map Evolutionary Processes This research is focused on fluid flow dynamics in porous material--more specifically in relation to nuclear waste contamination. It has recently been more focused on the development of mathematical models to predict disease progression, which includes HIV-1 dynamics, brain tumor progression, cholera colonization of the intestine, and early detection of specific antigens in the blood. While many of these projects are quite specific, the tools developed may be applied to mapping and predicting evolutionary processes in general. One of the projects that has spun out of the main effort focuses on the imaging, mapping, and progression prediction of brain cancer. The mathematical and statistical modeling is being integrated into a bioimplantable sensor for monitoring brain cancer. While this technology is still in a very early stage, it appears that there is at least a basic code that has been developed that is functional. Future work is focused on fine tuning the code and validating the brain cancer imaging and prediction function of the biosensors to allow for real time simulation. |
Embedded systems and Artificial Intelligence Derived Biosensor Devices This is application-driven research focused on the use of artificial intelligence and embedded systems in biosensors and imaging devices. One of the technologies that is being developed involves a device that traps and kills HIV infected cells. The device conceivably would be implanted into the lymph system and proactively recruit infected cells. Additionally, research is focused on a sensor to map the progression of brain cancer using 3-D mathematical modeling and an embedded systems approach. While these are early stage technologies, the architecture that enables functionality of the sensors involves the generation of a circuit without using a microprocessor. The research has yielded a way to use JAVA to create the circuit. This concept could have the potential to be used in a number of different applications, including wide use in the biosensor field. |
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. |
Applied Chemical and Morphological Analysis Laboratory The Applied Chemical and Morphological Analyses Laboratory (ACMAL) is a university facility that houses an extensive array of electron microanalytical and x-ray instruments. Electron beam instrumentation includes two scanning electron microscopes (SEM), a high-resolution transmission electron microscope (TEM) and a focused ion beam milling system (FIB). X-ray equipment includes a sequential x-ray fluorescence spectrometer and five x-ray diffractometers. |
Text, Image and Video Databases This research program focuses on a topics associated with motion analysis and object tracking, document image processing, pattern recognition and machine learning. More generally, issues under investigation include data mining in text, image and video databases as well as neural networks design and application. |
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. |
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. |
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. |
Multivariate statistics and models A broad range of statistical skills and knowledge is available for both basic and applied problems including statistical quality control, industrial and biostatistical applications. Specific areas of specialization included multivariate analyses and repeated measures as well as linear models and experimental design with a broad spectrum of application interests. |
µMRI Techniques for Detection and Investigation of Articular Cartilage This research program is generally designed to use high resolution MRI and other microscopic imaging techniques to study a number of important engineering, biological and biomedical problems. More specifically, the research is focused on detecting cartilage degradation, an early event in osteoarthritis using µMRI. The techniques developed are capable of a transverse resolution of 14 microns across the full depth of the cartilage tissue layer. This microscopic resolution allows examination of tissue properties in individual histological zones in cartilage non-invasively and non-destructively. |
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. |
Using Atomic Force Microscopy (AFM) to Analyze Surface Energy of Pull-off (Adhesion) Forces Atomic force microscopy (AFM) is capable of characterizing solid surfaces at the microscopic and sub-microscopic scales. As demonstrated in several laboratories in recent years, it can also be used to determine the surface tension of solids based on adhesion (pull-off) force measurements. Before AFM force measurements can become an accepted technique for particle-substrate adhesion characterization, individual problems causing irreproducibility of the measurement must be resolved. This is particularly important in the measurement of pull-off forces in very complex geometry systems that are of importance to the industry. For example, this research program has resulted in measures of the adhesion forces between pharmaceutical particles with irregular geometry and polymeric surfaces of varying roughness in a gas of controlled humidity level. |
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. |
Fibers and Composites for Orthopedic Applications This program of research interests is oriented toward fabrication and characterizing polymeric fibers and composites, particularly focused on orthopedic applications. As such, the program incorporates expertise for designing assistive technology devices. Extended capabilities include research on the nanomechanical properties of hot compacted composites and wear of hot compacted composites for total hip replacements, particularly, fabrication of low-wear materials for total hip replacements. The research program offers expertise in nano-mechanical properties of materials, the thermomechanical properties of polymers, fabrication and hot compaction of polymer fiber composites. |
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. |
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. |
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. |
Analyzing the Euglenoid Plastid Genome Dr. Eric W. Linton is analyzing the plastid genome of euglenoid protozoans. The chloroplast of land plants, site of photosynthesis and oxygen production in plants, was inherited from green algal ancestors. Euglenoid protozoans have chloroplasts that derive from green algae as well, but through an engulfment process whereby a host cell took in a green alga and retained it as part of the cell. Chloroplasts were probably gained and lost several times during evolution of modern euglenoids. By sequencing the complete chloroplast genomes of several euglenoid species that have chloroplasts and several that lack them, the researchers will gain insight into how many times chloroplasts were acquired and lost, and how the host genomes interacted with the chloroplast genomes during this process. Undergraduate and graduate students, as well as high school teachers, will be involved in hands-on research in genomics. An integrative software program for aligning DNA sequences will be further developed and distributed to the scientific community. Euglenoid chloroplasts contain genes found in disease-causing protozoans, and complete genome sequences should provide insight into the origins of these genes. |
Bioengineering and Health Informatics Oakland University hosts a ten week NIBIB-NSF Bioengineering and Bioinformatics Summer Institutes (BBSI) Program in Bioengineering and Health Informatics under the direction of Dr. Fatma Mili. This Institute will support a total of 60 undergraduate and graduate students, 15 per year for a total of four years.
The primary object of this Institute is to promote graduate studies and careers in bioengineering and bioinformatics to bright and talent students pursuing degrees in Computer, Natural, Health Sciences, and other related majors with a focus on enhancing career opportunities for African American and other minority students in the fields of bioengineering and health informatics. The students will be immersed in a comprehensive learning and research environment and will receive a two-week focused training session followed by eight weeks of full time research. Research will be conducted within a multidisciplinary team and encompasses the full life-cycle from defining the research problem, exploring multiple solutions, discussing progress with peers and wider audiences, and formulating findings and making conclusions.
This project is being co-funded by the Directorate for Mathematical and Physical Sciences (MPS)/Division of Mathematical Sciences (DMS), the MPS/Office of Multidisciplinary Activities (OMA), the Directorate for Computer and Information Science and Engineering (CISE)/Division of Information and Intelligent Systems (IIS), and the National Institutes of Health (NIH)/National Institute of Biomedical Imaging and Bioengineering (NIBIB). |
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. |
Undergraduate Research Center This is a planning project to integrate research into the curricula at community colleges and four-year colleges in southeast Michigan. In this phase, research experiences will focus on students from three community colleges: Wayne County Community College, Oakland Community College and Macomb Community College. Students will have 6 weeks of research training in the summer and will continue to do research on a part-time basis during the academic year. The research will center on environmental and chemical toxicology. Other activities during the planning phase will include development of criteria for evaluating applicants, development of introductory materials for the course on basic research skills, consideration of logistical and scheduling issues for students and discussion of avenues for sustaining the program. Meetings will be held with potential college participants to assess interest and potential program size. A high school outreach program will be integrated into the URC. |
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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