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DAVID
J. EARNEST
Assistant Professor
Cellular and Molecular Neurobiology of the Mammalian Circadian
Clock
The
internal biological clock responsible for the generation of
mammalian circadian rhythms and their entrainment to light:dark
cycles is located in the suprachiasmatic nucleus (SCN) of
the anterior hypothalamus. Research investigations in the
Earnest Lab have pioneered the identification of immediate-early
genes as key components of the pathway for circadian photoentrainment,
the development of immortalized 
as models for studying the cellular and molecular organization
of the SCN pacemaker, and analysis of relationship between
age-related changes in circadian timekeeping and SCN expression
of neurotrophins. Our current research focus is on studying
core molecular components of the circadian clock mechanism
in the SCN and SCN output signals. Analyses in this area will:
| 1) |
Utilize
cDNA microarrays to obtain a comprehensive picture of
transcripts that are regulated in a circadian fashion
(clock and clock-controlled genes).
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| 2) |
Develop
real-time, luciferase-reporting of circadian gene expression
in the SCN clock.
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| 3) |
Examine
the roles of candidate clock genes in the SCN clock mechanism
by determining whether rhythmicity in SCN circadian outputs
is disrupted when expression of these genes is experimentally
maintained at constant levels.
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| 4) |
Employ
co-culture techniques to determine what diffusible factors
from immortalized SCN cells are involved in the communication
of circadian outputs to other cell types and in the coupling
between individual pacemaker cells.
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Associated research interests include analysis at the behavioral
level using neural transplantation of immortalized cells to
determine what SCN cell types are necessary to restore the
circadian rhythm of wheel-running behavior in SCN-lesioned
host animals. Another prominent research area in the Earnest
Lab is centered on understanding how 24-hour environmental
signals, particularly light-dark cycles, synchronize circadian
rhythms. Research projects in this area employ molecular approaches
to examine the signal transduction pathway by which light
entrains circadian rhythms. These studies have yielded important
information on the roles of several immediate-early genes
and specific neurotransmitter signals in the pathway for circadian
photoentrainment. Experiments are presently exploring how
neurotrophins such as brain-derived neurotrophic factor ( )
may be involved in regulating the circadian sensitivity of
the SCN clock to light and in the deterioration of circadian
timekeeping that occurs in aging and Alzheimer's Disease.
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