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TRAINING
IN PHARMACOLOGY, TOXICOLOGY & PHARMACEUTICAL SCIENCES ASPET
SUMMER UNDERGRADUATE RESEARCH FELLOWSHIP OPPORTUNITY at the |
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The Department
of Pharmacology & Cell Biophysics, College of Medicine is pleased to
offer this research project as part of the 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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Faculty Supervisor/Mentor: John E. Maggio, Ph.D.
Professor
Pharmacology & 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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