DNA Technologies Core Director, Terry Thomas

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Transcript DNA Technologies Core Director, Terry Thomas

The sun; SOHO's EIT (Extreme-Ultraviolet Imaging Telescope)
Earth-moon system from Galileo-1990
(from NASA photo gallery)
The astronomer Jean Jacques d’Ortous deMairan is
usually credited with discovering “circadian rhythms”
in heliotrope plants in 1729
Properties of Circadian Rhythms
• Name is derived from “circa” (approximately) and
“diem” (day)
• When organisms are placed in constant conditions
of DD or dim LL, they express a circadian rhythm
with a period (t) of slightly less or slightly more
than 24 hrs
• These rhythms must be synchronized or
“entrained” to local time so that the phase (f) of
the internal rhythm corresponds to the f of the
outside world.
Prokaryotes such
as cyanobacteria (in this case
Synechococcus sp.) express
circadian rhythms in gene
expression with a t of about
24 hrs
(from Golden et al. 1999)
Fungi, such as the orange bread mold, Neurospora crassa, express
a wide varietyDiagram
of circadian patterns.
In thistube
case, patterns of
of a race
conidiation, or asexual spore formation, occur every 19-20 hrs.
Point of
one circadian cycle
24 hours of
(from Bell-Pedersen, 1999)
Complex, multicellular animals
express a wide variety of
circadian rhythms. In this case,
the activity/sleep and body
temperature patterns of a single
human subject is expressed
in actogram format. The average
t is 24.1-25 hrs
(from Aschoff, 1981)
What are Biological Clocks?
• Simply put, “biological clocks” are mechanisms
by which organisms can tell time. The enable
living things to predict internal and external
– Internal oscillator
– Zeitgeber or synchronizer
– Output pathways
• These clocks predict periods of varying magnitude
– Annual (circannual)
– Daily (circadian)
General Model of Circadian Clocks
Circadian Output
Clock Pathways Outputs
Input Pathway
The Hypothalamic Suprachiasmatic Nucleus (SCN) is the
Master Pacemaker for Nocturnal Rodents and Probably
Many, If Not All, Mammals
(from Bittman, 1984)
SCN 2.2 Cells Induce Circadian Rhythms in NIH3T3 Cells
(from Allen, Rappe,
Cassone and Eannest, 2000)
SCN2.2 Cells Restore Circadian Rhythms
NIH3T3 Cells Do Not
(from Earnest, Liang, Ratliff and Cassone, 1999)
Recent advances in
molecular genetics has
identified specific genes
that are important for
circadian rhythms in
many different types of
organisms that are
expressed rhythmically in
clock-associated tissues.
This is the expression
pattern of mouse period
genes in the SCN.
(from Maywood et al.
“Common” Elements of Circadian Clocks
Clock Genes
Output (CCGs)
Rhythmic Metabolism
And Behavior
Positive Elements in circadian
kaiA in Synechococcus
wc1 and wc2 in Neurospora
Clk, cyc, clock and bmal1 in
Negative Elements in
circadian loops:
kaiC in Synechococcus
frq in Neurospora
Per, cry and tim in animals
In Mammals, At Least, Pineal Rhythmicity Derives Primarily
From Rhythmic SCN Input via the Sympathetic Nervous System
(from Bittman 1984)
Pinealectomy has no effect of rodent locomotor rhythms in DD
(from Richter, 1967)
But Daily Administration
Of the Pineal Hormone
Melatonin Entrains Rat
Circadian Rhythms.
This Effect is Dose- and
Phase-Dependent with an
ED50 of 1-5 mg/kg (Cassone
et al. 1986; Warren et al. 1993),
Independent of the Pineal
Gland (Warren et al. 1993)
and Does Not Require
Injections (ie. Infusions
of Melatonin Work; Kirsch et
(from Redman, Ng, and Armstrong, 1983)
Circadian Rhythms in the
• Visit Website for the NSF Center for Biological
Timing to learn more about clocks
– http://cbt4pc.bio.virginia.edu/tutorial
• Also, there are specific classroom and home
activities listed in that site at
– http://cbt4pc.bio.virginia.edu/tutorial/CLASSACT.html
A copy of this presentation can be found at the following website
Visit the Biological Clocks Program
At Texas A&M at http://www.bio.tamu.edu/clocks/