October 8, 2008
4:00 pm
W118 Anatomy/Zoology
Reception in the lobby
[more information] |
Sensing Gases (NO vs. O2) Selectively in Biology: Chemistry to the Rescue
Dr. Michael Marletta
Aldo DeBenedictis Disinguished Professor of Chemistry
Professor of Biochemistry and Molecular Biology
University of California, Berkeley
Professor of Cellular & Molecular Pharmacology at UCSF
Faculty Scientist at Lawrence Berkeley National Laboratory |
Sensing Gases (NO vs. O2) Selectively in Biology: Chemistry to the Rescue
Work in Dr. Michael Marletta's laboratory lies at the interface of chemistry and biology with emphasis on the study of protein function and enzyme reaction mechanisms. Marletta and colleagues address fundamental biological questions that have broad applications in human health and disease. Discriminating between structurally similar, but functionally different gases like oxygen (O2) and NO (nitric oxide) is vital for most organisms. Cells bind and sense O2 via the heme domain of hemoglobin that cannot discriminate between O2 and NO. The enzyme "soluble guanylate cyclase" (sGC), in contrast, performs signaling interactions specifically with NO molecules critical to regulating blood pressure, and it can do so even though the similar diatomic gas O2 is usually present in excess. When NO enters a cell it activates sGC, which catalyzes the formation of cyclic GMP, a protein that relaxes and dilates blood vessels. The NO signaling pathway is also important for neuronal signal transduction and inhibition of platelet aggregation. The nematode C. elegans uses a similar H-NOX (heme-nitric oxide and/or oxygen binding) domain, in this case selective for O2, to orientate itself towards low O2 concentrations via a specialized sGC-like protein, GCY-35. For the worm, low doses of O2 indicate the presence of oxygen-consuming bacteria, its source of food in the petri dish. It is likely, that the carotid body, the small organ that monitors O2 levels in the human bloodstream, uses a similar O2-sensing mechanism.
Combining the tools of chemistry as well as molecular and structural biology, the Marletta lab has contributed significantly to our understanding of NO- versus O2-selective screening and its biological role in prokaryotes and eukaryotes. They also predicted and found specific amino acid changes that promote binding of one diatomic gas or the other. These detection mechanisms are fundamental processes and shed new light onto possible causes or treatments of a wide range of human diseases, including endocrine, cardiovascular, and neural dysfunctions.
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April 10, 2008
4:00 pm
A103 Chemistry
[more information] |
The Birth and Travels of RNA
Dr. Robert H. Singer, Ph.D.
Professor & Co-Chair, Anatomy & Structural Biology
Professor of Cell Biology, Professor of Neuroscience
Yeshiva University, Bronx, New York |
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Studying the Birth and Travels of RNA
Work in the Singer laboratory is focused on the expression and
travels of RNA within cells - from sites of birth to ultimate
biological destiny in the cytoplasm where RNA is translated
to make proteins in specific locations. Their new technology,
based on in situ hybridization, allows them to visualize specific
nucleic acid sequences within individual cells using high-resolution
digital imaging microscopy. The clinical application of this
technology allows, inter alia, for the molecular diagnosis of
cancer cells. As an additional result of this approach, they
have found specific RNA sequences located in particular cellular
compartments. As such, transcripts are not freely diffusing
but rather appear to be spatially associated with a cellular
matrix or skeleton from the moment of their synthesis through
translation. They are investigating how this spatial information
is encoded within the gene and how the RNA transcript is processed
within the nucleus and then transported to its correct compartment
in the cytoplasm. They have constructed genetically altered
cells to elucidate the sequences responsible for mRNA localization.
A reporter gene can be "delivered" to a variety of
cellular compartments by using specific sequences, or "zipcodes"
from the mRNAs found in those compartments. These "zipcodes"
consist of short sequences in the 3' untranslated region of
the mRNA. So far, Singer's group has isolated and cloned several
proteins that bind to "zipcodes" and decode their
information. Recently, they also developed a technology that
allows them to visualize fast RNA movements in living cells
to characterize how cellular motors connect with and drive the
RNA.
http://singerlab.aecom.yu.edu/people/rhs.htm |
