CIRCADIAN RHYTHMS

CIRCADIAN RHYTHMS Understanding how biological clocks control daily rhythms Dr. Brigitte Dauwalder Associate Professor Department of Biology and Biochemistry University of Houston

Rhythm (Circa Diem = Approximately a Day)

Geophysical cycles are the basis of daily biological rhythms The earth rotates on its axis once every 24 hours Daily cycles of -Light -Temperature -Humidity Very predictable changes Organisms have evolved to coordinate their activities with the day-night cycle

Jean Jacques de Mairan (1729)

Circadian clocks anticipate environmental changes

Circadian clocks controlling social behaviour Guy Bloch, Dan P. Toma and Gene E. Robinson

Annual geophysical cycles are the basis of seasonal rhythms The earth is tilted on its axis and revolves around the sun Seasonal changes correlate with changes in the ratio of light and dark each day Changes are very predictable

The monarch long-distance migration From Reppert et al, TINS 2010 Fall  Oriented flight south  Increased life span  Reproductive diapause Roosts College station

Circadian rhythms continue in a constant environment…biological clocks! Circadian clocks synchronize physiology, metabolism and behavior to the external environment, thereby enabling anticipation of daily environmental changes

Circadian rhythms are relatively insensitive to changes in temperature: They are “temperature compensated” In biochemical reactions, Q 10 = 2-3 For circadian rhythms, Q 10 = Q 10 = frequency at Temp 1 frequency at Temp o C

Circadian Clock Properties Entrained by environmental cues Light Temperature Food Social cues Rhythms persist in constant conditions periods close to 24 h. (circa-dian) Temperature compensated Can be used to tell time Sun compass orientation Seasonal breeding

Individual tissues have clocks too

How do circadian clocks keep time and control rhythms? Model Systems!

Measuring Locomotor Activity in Drosophila Days Time of Day (h) LD DD LD = Light/Dark Cycle DD = Constant Darkness

per 01 Konopka and Benzer, PNAS, 1971 The period mutants of Drosophila PAS A B per L per S TG

per mRNA and protein abundance cycle in a circadian manner Relative abundance Zeitgeber Time PER protein per mRNA

Per and tim genes Tim protein NUCLEUSCYTOPLASM Per protein Per mRNATim mRNA

Per and tim genes Tim protein Tim Protein active NUCLEUSCYTOPLASM Per mRNATim mRNA

Clock and cyc genes Clock protein Cyc protein Per and tim genes Tim protein Tim Protein active NUCLEUSCYTOPLASM Per mRNATim mRNA

Clock and cyc genes Clock protein Cyc protein Per and tim genes Tim protein Tim Protein active NUCLEUSCYTOPLASM Per mRNATim mRNA

Clock and cyc genes Clock protein Cyc protein Per and tim genes Tim protein Tim Protein active NUCLEUSCYTOPLASM Per mRNATim mRNA FEEDBACK LOOP

How do circadian clocks impact human health?

Smolensky and Lamberg, The Body Clock Guide to Better Health., 2000 Circadian rhythms in humans

Hatori et al. (2012) Cell Metab. Circadian clocks, feeding and obesity

Sleep time and social jetlag

Mammalian SCN

Maywood et al., Current Biology 2006 mPer1::Luc Oscillations in the SCN

Circadian rhythms also regulate our sleep patterns

The New York Times Goodnight. Sleep Clean.

THE CIRCADIAN CIRCUITRY Clock mechanisms are highly conserved between flies and mammals. In both mammals and flies, defined groups of genes and neurons controls circadian behavior. These neurons communicate to remain synchronized. Work in flies has influenced mammalian studies, and vice versa, with regard to thinking about circuit interactions in the circadian system (e.g., roles for neuropeptides). Much more needs to be discovered to really understand the circadian clock and how it influences our health !