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Adhesion
molecules:
Under normal circumstances, white blood cells (leukocytes) continuously
circulate the blood vessels, patrolling the body for signs of injury and
infection. Such immune surveillance kicks into immediate action when
tissue, damaged or colonized by disease causing microbes, is discovered by
these professional warrior cells. Leukocytes are first drawn from the
flowing blood to the sides of those blood vessels that have detected a
nearby problem. This "alluring" is carried out by a series of
overlapping adhesive interactions that occur between the leukocyte
receptors and the distress-signaling ligands newly expressed on the
surface of damage-activated endothelial cells. Once in the vicinity of the
troubled site, the previously non-adherent, round leukocytes attach to the
blood vessel wall, metamorphose into a sticky, flat and motile cell type,
leave the blood stream and migrate into the compromised tissue. There they
mop up the cellular debris, foreign substances and chemically attack any
invaders. While very rapid and often effective in eliminating the invading
microorganisms, this mode of defense all too often gets out of hand,
causing more harm than good. In fact, tissue damage caused by such
inflammatory overreaction accounts for hundreds of thousands of deaths in
the US annually. It is hoped that once we understand the mechanisms of
leukocyte recruitment to the inflammatory site, we can design drugs which
will interfere with specific steps in this inflammatory process and avoid
the currently deadly leukocyte overreactions
Immuno-modulation:
Our research has recently focused on the role of leukocyte adhesion
molecules in inflammatory target recognition. Elucidation of a specific
biochemical mechanism that causes inactivation of the adhesion-initiating
receptor L-selectin is leading towards development of novel
anti-inflammatory drugs. This biochemical model additionally predicts that
several widely used pesticides and pollutants will cause profound immuno-suppression
and perhaps infertility. Surprising implications of this model, including
the potential to interfere with the HIV entry into lymphocytes, are being
explored at the theoretical level.
Pathogen Detection:
A collaborative project with microbiologist Dr. Kieft in our department
and numerous other investigators at Yale University School of Medicine,
Pacific Northwestern National Laboratories, Battelle, Oak Ridge National
Laboratories, BioStar and Becton-Dickinson (BD), was recently funded by
the Office of Naval Research. This Pathogen Detection Program will utilize
hybrid technologies to develop an ultra sensitive means for detecting
pathogenic organisms in the
environment. It is envisioned that automated microarray
and immuno-PCR technologies will sense and identify relevant virulence
factors in the water air and food supply well before pathogens are
abundant enough to cause disease.
CO2
Sequestration: An average fossil-fuel burning power plant releases
about 300kg of CO2 into the atmosphere each second. This gas accumulates
and contributes to the global warming. A method for non-atmospheric CO2
storage is urgently needed. Carbonic anhydrase is a ubiquitous enzyme that
is capable of hydrating CO2 and forming bicarbonate.
Under correct conditions, and in the presence of a counter ion such as
calcium, calcium carbonate (limestone), is formed. Limestone is a permanent, non-toxic form of sequestered
CO2. In collaboration with Dr. Gillian Bond in in the Materials
Engineering department here at NM Tech, we are developing a bio-mimetic
approach to CO2 sequestration. Human carbonic anhydrase, overexpressed in
E.Coli, is being explored for its applications in
the control of CO2 emissions from power plants, as well as for pH
maintenance in sewage plants.
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