Periodic Reporting for period 4 - CIRCOMMUNICATION (Deciphering molecular pathways of circadian clock communication)
Reporting period: 2022-09-01 to 2024-02-29
The mammalian circadian timing system consists of a master clock in the brain and subsidiary oscillators in almost every cell of the body. Since these clocks anticipate environmental changes and function together to orchestrate daily physiology and behavior their temporal synchronization is critical.
The intricate nature of the mammalian circadian system demands the presence of communication mechanisms between clocks throughout the body at multiple levels.
While previous studies primarily addressed the role of the master clock in resetting peripheral clocks, our knowledge regarding the communication among clocks between and within peripheral organs is rudimentary.
Our overall objective is to uncover the circadian communication network between peripheral organs at a system-level and to identify novel communication routes at the molecular level.
In essence we found that oxygen and carbon dioxide rhythms are circadian clock controlled and differentially directed by behavioral signals. Moreover, we discovered that hypoxia induces a time- and tissue-specific response that elicits inter tissue circadian clock misalignment.
We also found that the liver-clock coordinates rhythmicity of peripheral tissues in response to feeding. Hence, providing new insight on the organization of the peripheral circadian clock system.
Finally, we developed Circa-SCOPE: high-throughput, live single-cell imaging method for analysis and identification of novel circadian clock resetting signals.
The impact of this research proposal extends far beyond circadian rhythms and bears great potential for research on communication between cells and tissues in various fields of biology and medicine.
Given that a wide variety of pathologies are associated with circadian misalignments (eg shift workers, Jet lag) studying circadian clock communication has important impact on our ability to understand the pathophysiology and identify potential remedies our ERC supported work set solid and important foundations for that.
The intricate nature of the mammalian circadian system demands the presence of communication mechanisms between clocks throughout the body at multiple levels.
While previous studies primarily addressed the role of the master clock in resetting peripheral clocks, our knowledge regarding the communication among clocks between and within peripheral organs is rudimentary.
Our overall objective is to uncover the circadian communication network between peripheral organs at a system-level and to identify novel communication routes at the molecular level.
In essence we found that oxygen and carbon dioxide rhythms are circadian clock controlled and differentially directed by behavioral signals. Moreover, we discovered that hypoxia induces a time- and tissue-specific response that elicits inter tissue circadian clock misalignment.
We also found that the liver-clock coordinates rhythmicity of peripheral tissues in response to feeding. Hence, providing new insight on the organization of the peripheral circadian clock system.
Finally, we developed Circa-SCOPE: high-throughput, live single-cell imaging method for analysis and identification of novel circadian clock resetting signals.
The impact of this research proposal extends far beyond circadian rhythms and bears great potential for research on communication between cells and tissues in various fields of biology and medicine.
Given that a wide variety of pathologies are associated with circadian misalignments (eg shift workers, Jet lag) studying circadian clock communication has important impact on our ability to understand the pathophysiology and identify potential remedies our ERC supported work set solid and important foundations for that.
Since the beginning of the project till now we made significant progress in understanding mechanisms that are implicated in circadian clock communication.
Our main findings are listed below:
1) The finding that oxygen and carbon dioxide rhythms are circadian clock controlled and differentially directed by behavioral signals.
2) The discovery that hypoxia induces a time- and tissue-specific response that elicits inter tissue circadian clock misalignment.
3) The finding that the liver-clock coordinates rhythmicity of peripheral tissues in response to feeding.
4) The development of Circa-SCOPE: high-throughput, live single-cell imaging method for analysis of circadian clock resetting.
5) The discovery that clock proteins and training modify exercise capacity in a daytime-dependent manner.
These findings have been published in high impact journals and presented in numerous scientific meetings around the world.
Our main findings are listed below:
1) The finding that oxygen and carbon dioxide rhythms are circadian clock controlled and differentially directed by behavioral signals.
2) The discovery that hypoxia induces a time- and tissue-specific response that elicits inter tissue circadian clock misalignment.
3) The finding that the liver-clock coordinates rhythmicity of peripheral tissues in response to feeding.
4) The development of Circa-SCOPE: high-throughput, live single-cell imaging method for analysis of circadian clock resetting.
5) The discovery that clock proteins and training modify exercise capacity in a daytime-dependent manner.
These findings have been published in high impact journals and presented in numerous scientific meetings around the world.
By accomplishing this ERC project, we addresseed a fundamental aspect of circadian biology, namely how billions of clocks in the body function in unison. This research project unraveled key aspects of the circadian communication network and identified molecular mechanisms through which circadian clocks communicate with each other under physiological and pathological conditions.