• Question: how do cells keep time in the first place?

    Asked by lewis to Nina on 14 Jun 2019.
    • Photo: Nina Rzechorzek

      Nina Rzechorzek answered on 14 Jun 2019:

      A ‘molecular clock’ exists in every cell in the body (including cells of the brain); if you take cells out of the body and culture them in a dish the lab without any external timing cues, their ‘clock’ will still cycle with a frequency of around 24 h. We’re still not exactly sure how this works, but we know it’s very important to cellular health, and ultimately, the health of the organ (and organism) those cells came from.

      Most organisms display ~24-hour cycles in their biology. In humans and other animals, these circadian rhythms result from daily timing mechanisms in every cell that together function like a biological clock; allowing our physiology to anticipate and prepare for the differing demands of day and night. Normally our biological clock is fine-tuned each day by the schedule we keep, particularly the timing of meals and light exposure. When we see bright light or eat at the wrong biological time, as often occurs during shift work or jet-lag, it disrupts our biological clock and increases the risk of chronic illnesses such as type II diabetes, cardiovascular disease and some cancers. On the other hand, the effectiveness of some drugs and surgeries can vary with the biological time of treatment. Understanding the molecular mechanisms that impart daily rhythms to our biology is therefore important for understanding human health and may provide new insights into the prevention and treatment of many diseases.

      Our current research is focused on understanding the fundamental mechanisms of daily cellular timekeeping and how circadian regulation of biological function is achieved. To achieve these goals we employ a wide range of molecular biology, proteomic, metabolomic and biochemical techniques, supported by real-time fluorescent and bioluminescent reporters.

      What we know already is that circadian rhythms in cellular function are synchronised by extracellular timing cues and supported by daily cycles in the activity of transcription factors encoded by clock genes, such as Period1, 2 & 3. Clock proteins suppress their own production via transcription-translation feedback loops (TTFL), whereas their translation, activity and stability are regulated post-translationally.

      You can see some schematics and cellular rhythms in action here:

      John O’Neill