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Find out more about
our lab's Research:
Our
Research Themes
& Experimental Approaches
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Research in our NSF-funded
program focuses on the development of physiological processes in animals, including amphibians, reptiles, fishes,
birds and the nematode C. elegans. In particular,
we are investigating the ontogeny of regulation of the physiological systems
along the life continuum of eggs, embryos, larvae/fetuses and adults.
We are unabashedly opportunistic, using animals that, according to the
Krogh principle (or some would say Bernard principle) help us solve
experimental problems. The earlier in development, the more
similar are all vertebrate animals, and the more we can generalize about
"the vertebrate" and identify general principles of
physiological development.
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Of special
interest is the interplay between
environment and development, how the environment shapes emerging
phenotype, and the extent to which the developing organism can exhibit
"self-repair" at the tissue, organ and organismal
levels. We typically raise populations of developing animals
under challenging environmental conditions, to learn if and how the ultimate
phenotype is independent of, or linked to, environmental experiences
earlier in development.
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As
you will determine from our
publications and our lists of lab
members and
collaborators,
we are investigating a wide range of physiology including:
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cardiac
development and function
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vascular growth and
development
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metabolic competency
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respiratory system growth,
and the transition from system to system in bi- or tri-modal breathers
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hypoxia tolerance
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hematopoeisis
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renal development
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thermoregulation
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Typically, we chart the development of basic physiological processes
such as the onset of heart
beat, development of blood pressure and flow, and gill or lung ventilation.
We then determine when and how the cardiovascular and respiratory systems come
under neural and endocrine regulation, and how these regulatory processes may
change with major developmental events such as hatching (birds, reptiles) or
metamorphosis (fishes, amphibians).
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We further investigate what factors can
shape and influence the normal developmental trajectories for physiological
regulatory mechanisms. Once the developmental timing of these events is known,
we will determine the critical windows during development in which these
systems are particularly susceptible to environmental perturbations of
temperature, oxygen availability, acidity, etc..
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An expanding part of our program
investigates the physiological genomics of the trans-generational transfer
of hypoxia tolerance, through both metabolic and physiological
mechansisms, using various strains of the fruit fly Drosophila
melanogaster.
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Our experimental approach is
broadly
comparative by design. By contrasting and comparing regulatory
mechanisms in a developmental series of a wide variety of animals, we can
distinguish fundamental developmental processes from those
processes that have evolved in the early developmental stages of only
particular taxa. In this context, our studies of developmental physiology
merge with our lab's additional interests in the evolution of
physiological processes.
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Our Animal
Models
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What is an "animal
model"?
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The animals listed below are employed in
various projects in our laboratory. Some of them are true
"animal models", to help us learn more about vertebrates in
general, and some are interesting animals deserving of investigation in
their own right.
- Why so many different models in our lab,
when most labs are "fly labs", "mouse labs", etc?
We are interested in the onset of physiological regulation during early
development. At these early stages, most of the species below are
qualitatively indistinguishable, yet each offers some advantage -
transparency, gigantism, life cycle time, etc. At the end of the day,
we can compare projects, and we are slowly weaving a tapestry that is
represent of vertebrate physiological development.
Our Mammalian Models
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Nine-banded
Armadillo
(Dasypsu
novemcinctus)
You
gotta love the armadillo! Apart from being the only mammal besides
man to carry the bacterium causing leprosy, they also show the
phenomenon of polyembryony. Shortly after fertilization,
the blastula divides into buds that continue to develop as individuals,
and each armadillo litter of four is invariably a clonal group with
identical genetic make up. We use armadillos to look
at between- and within-litter variation in physiological characteristics.
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Our
Avian Models
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Emu (Dromaius
novaehollandiae)
The emu lays
eggs that typically weigh from 650-800 g, about 12-15X greater than a
chicken egg. Fortunately, the embryo and all of the extra-embryonic
structures are also scaled up by more than an order of magnitude.
This makes possible surgical procedures that just can't be done in
conventionally studies bird eggs (chicken, quail).
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Chicken (Gallus
gallus domesticus)
Serving as
one of the main models for physiological development for decades, if not
centuries, we are using the chicken embryo to map the ontogeny of
cardiovascular, respiratory, and metabolic in chicken embryos under
hypoxic and thermal challenge.
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Quail
(Coturnix coturnix)
Though the eggs of the quail are quite small, this species represents
avian development "in the fast lane", hatching after just 16
days of development. In this regard, it makes for a useful
comparison with chickens (21 day incubation) and emus (51 day incubation).
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Our
Reptilian Models
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Various Species
The
eggs of many reptiles present wonderful opportunities for exploring how
environment (specifically, the hydric environment) influences
development. For example, by adjusting the water potential of
the medium in which the eggs are incubated, the water content of the egg -
and the blood volume of the embryo - can be manipulated. We have
used thes animals in the past to determine how the cardiovascular system's
baroreceptors begin to function and reach their set-points.
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Our Amphibian Models
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Bullfrog (Rana
catesbeiana)
The bullfrog has long been a standard for developmental physiology, in
part because of the large, easily available larvae
(tadpoles). In fact, our physiological knowledge of
development for the bullfrog rivals that of the chicken. Their
wonderful transition from pure water breathers (initially skin, then skin
+ gills), to combined water and air breathers (skin + gills + lungs) make
them an ideal subject for evo-devo studies.
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Coqui (Eleutherodactylus
sp.)
The genus Eleutherodactylus is the single largest vertebrate genus,
and each of the >450 species is a direct developer. The
pea-sized, transparent, terrestrial eggs hatch to reveal a perfectly
formed miniature adult. Because the eggs are transparent, wd can
monitor cardiac function from first beat through "metamorphosis"
within the egg to hatching with the adult morph.
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African
Clawed Frog
(Xenopus
laevis)
Xenopus
is the amphiban equivalent of the chicken or the zebrafish
with respect to being a prominent developmental model. The
normal physioloigcal ontogeny has been well characterized, and our studies
now focus on how environmental challenge perturbs normal development, and
how the animal in turn copes.
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Our Fish Models
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Zebrafish (Danio rerio)
A relative newcomer yet an incredibly popular model in developmental biology, the zebrafish has
also proved very useful in developmental physiology studies. Among
other advantages, this teleost fish native to streams in India, is a
prolific breeder, producing hundreds of tiny, transparent eggs. Because the
heart and circulation can be seen through the translucent body wall for
the first 10 days after hatching, we can use optical methods can be used to measure cardiac
output, red blood cell velocity, and blood vessel growth and diameter, to
name a few. Of course, there is the matter of the embryos
weighing only 1/10 mg at hatching, but we have long been on the lunatic
fringe in terms of measuring physiological performance in vanishingly
small animals......
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Blue
Gourami
(Trichogaster
trichopterus)
Very
little is known about the developmental physiology of the blue gourami
(there have been some papers on the respiratory and metabolic adult
physiology),
but it has great promise because of its ease of breeding in captivity, its
rapid growth, and its obligatory air breathing habitat early in
development.
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Our Invertebrate Models
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Drosophila melanogaster
The fruit fly Drosophila melanogaster provides a
complex metazoan that nonetheless has a short generation time.
This makes it ideal for our studies of physiological and metabolic
maternal effects, the non-genetic transmission of characters from
parents to offspring.
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Caenorhabditis
elegans
The nematode C.
elegans is an increasingly popular invertebrate model with which
to study genomics, including physiological genomics. Its short
generation time (a few days), ease of cultivation, simplicity (just 959
cells), and increasingly well-understood genetics make it a powerful model
for investigating the genetic underpinnings of basic physiological
process such as metabolism and locomotion.
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Our Methodologies
and Expertise
Methodologies and techniques
we employee in our laboratory include:
- respirometry, both aerial
and aquatic, including microrespirometery of individual eggs/fry/larvae
- blood pressure measurement
- conventional and "servo-null" micropressure systems
- blood flow (pulsed Doppler)
- blood analysis - O2,
CO2, pH, acid-base, [Hb], P50, hematocrit, etc.
- in situ
hybridization for VEGF
- microscope image analysis
for in vivo determination of heart rate, cardiac output, blood
velocity, vascular diameters, vascular growth
- microinjection/microwithdrawal
for drug injection/blood sampling
- specialized avian egg
incubation facilities for hypoxia/hyperoxia
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