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TRAINING IN PHARMACOLOGY, TOXICOLOGY & PHARMACEUTICAL SCIENCES 2008 ASPET SUMMER UNDERGRADUATE RESEARCH FELLOWSHIP
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The Department of Pharmacology & Cell Biophysics, College of Medicine is pleased to offer this research project as part of the 2008 summer ASPET SURF Training Program offered by the Department of Pharmacology & Cell Biophysics. Students interested in this project are advised to contact Professor Maggio to discover more about the project, learn what your responsibilities will be during the ten-week research training program. |
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2008 ASPET SURF Project #: 08 - 003 Faculty Supervisor/Mentor: John E. Maggio, Ph.D.ProfessorPharmacology & Cell Biophysics
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Project Title: Novel Probe Candidates for In Vitro and In Vivo Imaging in Alzheimer’s Disease |
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Research Program Description: The general research goal of Maggio’s lab is to understand the behavior of bioactive peptides and their receptors, in the nervous system and elsewhere. Bioactive peptides are the largest and least understood class of intercellular messengers, carrying out a diverse set of functions in a wide variety of systems. One system of interest is the tachykinin (substance P) family of peptides and receptors, which are involved in transmission of primary afferents and thus in pain and neurogenic inflammation. As the primary structures of both the ligands and their receptors are known, an excellent model system for peptide-protein interactions in signaling is available. Recently Maggio’s laboratory has identified through photoaffinity labeling which regions of the peptide substance P interact with which regions of its G-protein-coupled receptor, a protein whose expression is upregulated a thousand-fold in some inflammatory diseases. Another system under active investigation is the process of amyloid formation in Alzheimer's disease (AD) and other amyloidoses. The characteristic lesion of AD is brain senile plaques formed mainly of the human amyloid peptide Ab. By reconstituting plaque growth (deposition of Ab at physiological concentrations onto authentic plaques) in vitro, we can characterize the process and identify conditions and components which enhance or inhibit its kinetics. Structure/activity studies have identified amino acids critical for amyloid deposition. The latter studies have further identified conformational elements essential to plaque deposition. A third research interest is the characterization of novel bioactive peptides from natural sources. A particularly rich source is the skin venom of certain neotropical frogs. The peptides found here include antibiotics and toxins as well as close analogs of discovered and yet undiscovered mammalian neuropeptides. |
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ASPET SURF Project Description: Alzheimer’s disease is a major public health problem, affecting 50% of the population ages 85 and older and causing the majority of dementia. Currently there are no truly effective objective diagnostic methods for the disease. Several peptide-chelate derivatives have been synthesized as potential imaging agents to detect and quantify the amyloid lesions on AD. Following established procedures (see Maggio et al., Bioconj. Chem. 13: 276-284), these novel probe candidates will be used by the ASPET SURF student for imaging in human AD brain sections in vitro. The ASPET SURF student will assay probes that work well in vivo in rodents in vivo. Methods include radioisotope labeling, peptide purification, autoradiography, and gamma camera imaging. Experimental design and scientific method will be emphasized. The student will be challenged and guided to read the scientific literature, will interact with scientists at various levels (graduate students, postdoctoral fellows, junior faculty and faculty) and participate in journal clubs. The student will be guided in scientific writing and will have the opportunity to earn authorship when the studies are published. |
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