Center for High Performance Scientific Computing (CHIPS-Comp)  A Beowulf-type cluster of 20 dual Alpha EV6 833, 750 and 667 MHz workstations with a Scalable Coherent Interface (SCI) network accelerates the progression of parallel programming tasks and exchange of information across the processors. This architecture allows for an extremely powerful supercomputing capability that may be used by researchers in diverse fields to process data at rates not achievable with conventional computing systems. The center can support research in materials science, nuclear physics, parallel computing, and can offer know-how as well as consulting services in material science and nuclear physics and access to computational methods development expertise. |
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. |
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. |
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. |
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). |
Using Maize as a Model System to Study a Novel Family of Helitron Related Transposable Elements Transposable elements have played an integral role in evolution and they constitute the most abundant entities in the eukaryotic genome. Helitrons are a recently-discovered family of transposable elements that apparently transpose through replication and strand replacement. Despite their abundance, there is no direct genetic evidence or proof for the existence of an autonomous Helitron. The investigators recently described two maize mutants that were caused by Helitron insertion and provided the first evidence that an active Helitron may reside in the present-day maize genome. This Small Grant for Exploratory Research will establish the direct genetic evidence of an active Helitron. This is high-risk project because the assertion that these maize mutants are caused by relatively recent insertion of Helitrons is based on the assumption that these were isolated in the 1900s. However, there remains a remote possibility that these mutants may represent remnants of ancient alleles that were not discovered earlier. The approach is potentially high pay-off because understanding the mode of transposition of this novel family of transposable elements may yield tools for crop improvement and provide novel insights into genome structure and organization. The objective of the project is to genetically identify the autonomous Helitron by monitoring various maize lines for somatic and heritable reversion events. This is essential in order to definitely identify an autonomous element and establish maize as a system to study the transposition of Helitrons. Broader Impact: The proposed research will provide interdisciplinary training opportunities for both undergraduate and graduate students in Genetics, Molecular Biology and Bioinformatics and reach out to high school students involved in the field experiments. A new course has been developed specifically to integrate Bioinformatics into the mainstream undergraduate and graduate curricula at Oakland University. The students will gain hands-on experience in gene discovery and annotation of sequence data generated by the proposed research. |
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. |
Integrating Bioinformatics Concepts in Computer Science Curricula: A Cognitive Assessment Driven Strategy This project introduces the concepts of a new multidisciplinary field (bioinformatics) within the existing computing curriculum by incorporating research-oriented, self-contained learning modules. Prospects for majors in the field of bioinformatics are expanding, including opportunities for graduate study and employment. This project fulfills this demand by introducing the notion of self-contained modules that encapsulate not only the core biological principles necessary to fully appreciate the computational aspect of the subject, but they also provide theoretical and practical exposure to the related computational biology algorithms and research areas. Graduates who know how to identify and work on solving leading research problems gain the significant benefit of being able to apply bioinformatics to a broad range of problems. In addition to being immersed in a burgeoning research sector, graduates of this program, who have free access to the newest knowledge and skills in the field as it evolves, may enjoy a competitive advantage in the workforce. Specifically, this project involves developing five lecture series. Each lecture series is comprised of 2-3 lectures and 1-2 laboratory modules devised for integration within the existing courses. The modules are designed with the objective of serving as academic examples of some of the computer science concepts covered in courses such as databases, analysis of algorithms, networking, data structures, etc. Thus, the main goal is to have a CS major cognizant of the computational challenges in bioinformatics. These modules all have some common characteristics. They are self contained, designed to be delivered with 3 to 4 hours of student contact, present the bioinformatics research concepts within a computer science context, incorporate a hands-on laboratory component, and integrate cognitive assessment with the objective of helping students appreciate the depth of their understanding of new concepts taught. The modules include: BINF 01 - The Biological Database Lectures Module (Biological Databases, GenBank Schema, Biological Database Federation, Biological Databases and Federation Architecture); BINF 02 - The Information Retrieval Lectures Module (Sequence Similarity Algorithms in Bioinformatics, Bio-Database Indexing Strategies, Genome Database Search Algorithms, Searching Genomic and Protein Databases with BLAST); BINF 03 - The Intelligent Models for Mining Biological Data Lectures Module (Computational Models of Biological Sequence, Hidden Markov Models for Biological Patterns, Machine Learning Paradigms applied to Bioinformatics, Applying Hidden Markov Models for Sequence Analysis, Information Theoretical Measure of Surprise); BINF 04 - The Adaptive Middleware Lectures Module (The Bioinformatics Open Source Project, CORBA and BioCORBA, Java Servlets and Distributed Annotation Systems, Internet Sequence Analysis with BioJava and BioPerl, Dazzle Servlet and DAS); and, BINF 05 - The Evolutionary Tree Computation Lectures Module (Computational Complexity of Constructing Evolutionary Trees, Cluster Based Methods for Evolutionary Tree, Hamming Distance and Parsimonious Trees, PHYLIP - The Phylogenetics Analysis Program). |
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