Transcript Biological Clocks, Oscillators, Rhythms…

Biological Clocks, Oscillators,
Rhythms…
Just generally, Time.
or, Of Zeitgebers, Pronking, frq, tim, per, clk, Leeches,
…and Other Fun Words.
Where we’re going…
• Examples of oscillators (heart, breathing,
pacing neural signals, circadian rhythms,
hibernation cycles, cell division cycle)
• What controls them?
• Internal vs external driving forces
• Timing in development
Why we need time.
1. Development. When should which cells turn
into what? What order should things
happen? How do they know when to
differentiate? What about life events?
(Maturity, etc).
2. Normal, daily life involves cycles. Cell
division, metabolism, sleep, hibernation,
heart beats, regeneration of cells.
Neurospora, a
unicellular fungus. It
has different cell
types.
Cycles First.
• Lots of different “clocks” in most
organisms.
• Can have more or less central control (SCN
- superchiasmatic nucleus - in mammals;
different organs have different clocks;
different feedback loops in even unicellular
organisms)
Circadian genes
• Most studied (sleep disorder implications,
etc)
• WC, frq in Neurospora
• clk, bmal, per, cry in mammals
• per, tim, cyc, clk in Drosophila
• These genes are similar, and form similar
feedback loops. Several of them are related.
Key elements:
• Something that inhibits itself either directly or
indirectly (allows for the delay)
• Degradation or some other “reset” cue
• In most cases, the ability to reset to external
conditions but to keep functioning without
external impetus
• Outputs that regulate other cell functions
Note: control takes place at
different stages
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Transcription
Translation
Protein functionality
Speed of degradation
We can tell what’s happening based on
which concentrations change (mRNA,
protein, etc)
What do these clocks regulate?
• Gene expression!
• Metabolism!
• Behavior!
Similar mechanisms operate
on smaller scales to regulate
smooth muscle contraction,
neural firing, liver activity,
and other processes.
External cues can reset the clock
• Light induced changes in protein
conformation (that allow or block other
molecules binding)
• Light induced degradation of molecules
• Most effective at dawn/dusk usually
• Other factors that can reset different
oscillators: temperature, nutrient
concentration, length of day
Leech Heartbeats
• Chemical pathways aren’t the only
oscillatory systems in biology. Electrical
oscillations (eg in nerves) play a role. Also
in development, perhaps.
• Some nerves inhibit the firing of others in a
cyclical way --> regular pattern
• 2 possible modes; can switch between them
Development: we need a way to
keep track of time…
• Oscillators, counters. For example, cells
that form the vertebra in embryos may
undergo different numbers of oscillations in
certain chemicals, which could play a role
in differentiation.
• “Timers”: threshold concentrations that
make a process start or stop (can be
temperature dependent).
Somite formation in embryos. Differentiation
may be a result of experiencing different
numbers of oscillations in PSM concentration
during formation.
The Cell Cycle as Timer
• Cell division  lower concentrations of
certain chemicals  cell differentiation
• Several examples:
– Kickstart expression of embryonic genes
– Transition from cell division to cell
differentiation
– Hox gene expression
Other examples:
-in mice, build up of a certain protein (p27kip1, which blocks
transition from G1 to S phase in cell division) eventually stops
the cell cycle and leads to differentiation rather than further
division
Pronking Springboks
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Another type of electrical coordination/oscillation. All the legs are in phase!
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http://www.youtube.com/watch?v=8Ba3UxqXiXU
Sources
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http://inls.ucsd.edu/~lev/gene/
http://www.hhmi.org/biointeractive/media/SCN-lg.mov
http://www.daviddarling.info/images/cell_cycle.jpg
http://ajpregu.physiology.org/cgi/content/abstract/246/6/R847
http://www.fgsc.net/Neurospora/sectionB3.htm
http://jn.physiology.org/cgi/content/abstract/91/1/382
http://jn.physiology.org/cgi/reprint/87/3/1572
http://jbr.sagepub.com/cgi/reprint/19/5/414
http://template.bio.warwick.ac.uk/staff/amillar/andrewM/Jo%20Selwood%20site/cogs_of_clock.htm#Negative%20fee
dback
Olivier Pourquie, “A Biochemical Oscillator Linked to Vertebrate Segmentation.” In G. B. Müller and S. A. Newman,
Origination of Organismal Form: beyond the gene in developmental and evolutionary biology. Chapter 11.
http://farm2.static.flickr.com/1434/970206932_e41c64ee04.jpg
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http://images.smarter.com/blogs/clock1.jpg
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http://mirror-us-ga1.gallery.hd.org/_c/flowers/_more2003/_more09/flower-Holland-Netherlands-RF.jpg.html
http://staffwww.fullcoll.edu/tmorris/elements_of_ecology/images/chipmunk_hibernating.jpg
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http://akvis.com/en/sketch-tutorial/wolf-colorsketch.php&h=336&w=500&sz=30&hl=en&start=2&um=1&tbnid=mrcypLBWAycaYM:&tbnh=87&tb
nw=130&prev=/images%3Fq%3Dwolf%26um%3D1%26hl%3Den%26client%3Dfirefoxa%26rls%3Dorg.mozilla:en-US:official%26sa%3DG
http://www.worldmigratorybirdday.org/2007/images/stories/wmbd/alyn_walsh.jpg
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