jet-lag - inria
TRANSCRIPT
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LD12-12
Jet-lag
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SG1
G2 M
Physiological and therapeutic control exerted on:- transitions (checkpoints) between phases (G1/S, G2/M, M/G1)- death rates (apoptosis or necrosis) and progression speeds inside phases- exchanges between quiescent (G0) and proliferative phases (G1 only)
Mitotic human HeLa cell (from LBCMCP-Toulouse)
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(from B. Basse et al., J Math Biol 2003)
di , Ki->i+1 constant or periodic w. r. to time t (1 i I, I+1=1)
ni:=cell population density in phase i ; vi :=progression speed; di:=death rate;
Ki-1->i:=transition rate (with a factor 2for i=1)
Flow cytometry
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=CDK1 All cells in G1-S-G2 (phase i=1) All cells in M (phase i=2)
Entrainment of the cell division cycle by = CDK1 at the circadian period
time t
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23 23 7 7 11
Arb
itrar
y un
its
Time (h)
NPV
Pineal
Lévi, Lancet Oncol 2001 ; Mormont & Lévi, Cancer 2003 (from Francis Lévi, INSERM U 776 Rythmes Biologiques et Cancers)
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20 000 coupled neurons, in particular electrically (coupling blocked by TTX),each one of them oscillating according to a period ranging between 20 et 28 h…
…resulting in an endogenous periodicity of the central circadian oscillator, but with entrainment by light (through the retinohypothalamic tract) for VL neurons
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Vs : Vs =1.6 (1+L cos(2 t/24)) target of entrainment by light L; K: target of transcriptional inhibition (e.g. by cytokines); Vm(i): the carrier of variabilility of the oscillatory period. 3 variables for the ith neuron that communicateswith all other (j i) neurons of the SCN throughcytosolic PER protein, with coupling constant Ke:electric? gap junctions? VIP / VPAC2 signalling?
(from Aton & Herzog, Neuron 2005)
(after Leloup, Gonze, Goldbeter, J Biol Rhythms 1999)
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Desynchro D/D (T: varying around 21h30)
Desynchro D/D (T: varying around 21h30)
Synchro L/D (entrainment at T=24h)
Resulting Per to control Wee1, hence CDK1= , in proliferating cells
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0 1 2 3 4 5 6 7
0
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100
150
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250
0 1 2 3 4 5 6 7
0
50
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0 1 2 3 4 5 6 7
34
35
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0 1 2 3 4 5 6 7
34
35
36
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38
39
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LD12-12
Jet-lag
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Desynchro D/D (T: varying around 21h30)
Desynchro D/D (T: varying around 21h30)
Synchro L/D (entrainment at T=24h)
Resulting Per to control Wee1, hence CDK1= , in proliferating cells
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Cyclin
P+
P
M+
X+ X
M
i d
1
2
3
4
cdc25
wee1
Cyclinprotease
Cdc2kinase
Mitotic oscillator model by Albert Goldbeter, 1997, here with circadian entrainment by a square wave standing for Wee1
(after U. Schibler,Science, Oct. 2003)
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LD12-12
Jet-lag