|
| NEURO
AND DEVELOPMENTAL TOXICOLOGY RESEARCH CORE
Research Focus of
the Core
The Neuro and Developmental Toxicology Research
Core within the MFBS Center at Oregon State University builds
on the collective research programs of five well-established investigators.
This assemblage links and establishes synergisms between the laboratories
of a natural products chemist, a neuropharmacologist, a cell biochemist,
an aquatic toxicologist and a molecular toxicologist. Moreover,
a cohesive program is evolving among and between these investigators
to discover and describe the properties of new neurotoxins from
marine microalgae and other aquatic sources. Marine neurotoxins,
particularly those from microalgae, are of increasing occurrence
and impact on human health and the economy of many coastal marine
environments, and consequently, there is a compelling need to
detect, isolate, and characterize the structures, pharmacology
and toxicology of new neurotoxins in advance of additional toxin
outbreaks. Ongoing work in three of the participating laboratories
of this new core has demonstrated that previously unstudied marine
microalgae are rich in structurally unique neurotoxins, and that
they illustrate interesting and insightful pharmacologies, For
example, it has been found that one of the toxins characterized
by this group, antillatoxin, is an activator of mammalian voltage
gated sodium channels at a new drug binding site, and this is
leading to new hypotheses concerning the molecular topology and
drug site interactions in this important ion channel complex.
Our newest members of the Research Core, Drs. Larry Curtis and
Robert Tanguay, will contribute the zebrafish model to help elucidate
the underlying mechanisms of neurotoxicity and developmental toxicology
of environmental chemicals and new neurotoxins. The unique characteristics
of this model can be used, for example, to evaluate the effects
of environmental neurotoxins on CNS development and function.
The proposed work will provide advance information concerning
the chemical and biological properties of new environmental neuro-
and developmental toxins, which will improve the quality and rapidity
of societal responses to new toxin outbreaks. Moreover, as the
currently known marine-derived neurotoxins provide a pivotal set
of tools for studies in cell biology and neuropharmacology, the
investigations of this core are contributing, and will continue
to contribute, new molecules to be used as such molecular probes.
Areas of Interaction
|
Bill Gerwick collecting cyanobacteria |
The Neuro and Developmental Toxicology Research
Core has been organized around the concept of several established
investigators contributing their respective areas of scientific
and technical expertise to study a significant area in environmental
human health. Specifically, Murray, McFadden and Tanguay will
lead the primary and secondary efforts to screen marine microalgal
extracts supplied by Gerwick for the presence of neurotoxic metabolites.
Gerwick will lead the isolation of new neurotoxins using bioassay
data of fractions provided by Murray, McFadden and Tanguay. Dr.
Curtis will lead efforts on the developmental and neurotoxicity
of chemicals in aquatic environments. Structure elucidation will
be performed by the Gerwick laboratory. Pharmacological mechanism
of action studies will be led by Murray, while McFadden will examine
the biochemical mechanism of action in the innovative fish scale
melanophore system. Tanguay will investigate the CNS toxicological
mechanism of action of new neurotoxins, and Curtis the developmental
toxicity. Hence, there is and will continue to be substantial
scientific interaction between all participants of this Research
Core.
Overall
programmatic coordination of the Neuro and Developmental Toxicology
Research Core will be the responsibility of the director, Bill
Gerwick. The Facility Core supporting this effort, a Structural
Chemistry core will also be under the direction of Bill Gerwick.
Bimonthly meetings of the Core participants, using speaker phone
connections for distant participants (Murray), will ensure that
all participants are up-to-date with the work and will maximize
the synergistic features of the core. Bi-annual research retreats
with all MFBS Center Investigators plus the annual external review
will allow further periodic review of the data and focus of the
program. Report writing and oral and written presentations of
the work represent additional opportunities for interaction between
core participants. Additional meetings between members of this
core will focus on writing grant applications; for example, a
successful R01 NIH grant was constructed and funded between Murray
and Gerwick during this past cycle of the MFBS Center.
|
