Available Positions

Circadian clocks are key regulators of daily physiology and metabolism in mammals. Our understanding of the role of the circadian clock and specific clock proteins in controlling exercise capacity is rudimentary. Consequently, there is growing interest in exercise biology in general, specifically in its interaction with other processes that govern whole-body physiology and metabolism. We have reported that mice show a day-time variance in exercise capacity, and it is affected by exercise intensity and clock proteins and elicits a distinct muscle transcriptomic and metabolic signature. Specifically, we demonstrated that ZMP, an AMPK activator, is induced by exercise in a daytime-dependent manner. We continue to study various aspects of exercise physiology through the lens of circadian biology (Ezagouri et al., Cell Metabolism, 2019; Adamovich et al., Proc. Natl. Acad. Sci., 2021.).

Our lab has a longstanding interest in circadian clock resetting. We previously have identified and characterized novel resetting cues such as hypoxia and CO2. Recently, we have developed a new method to study resetting agents in vitro in an efficient and high-throughput manner, dubbed Circa-SCOPE. The method allows screening of multiple drugs in parallel to identify which affects the clock and how. Hence, it opens the door to a wide range of basic and translational research opportunities.

We demonstrated that low-amplitude oxygen cycles, which mimic the daily physiological cycles in oxygen levels observed in rodents, can reset the clock in a HIF-1a-dependent manner (Adamovich et al., Cell Metabolism 2017). Subsequently, we showed that oxygen and carbon dioxide rhythms are circadian clock controlled and differentially directed by behavioral signals (Adamovich et al., Cell Metabolism 2019). More recently we found that hypoxic conditions, as occur in sleep apnea, elicit circadian misalignment between clocks in different peripheral organs (Manella et al., P.N.A.S. 2020). We continue our venture to study the cross-talk between oxygen and circadian clocks at different levels.

• Clocks resetting | Recently, we have developed a new method to study resetting agents in vitro in an efficient and high-throughput manner, dubbed Circa-SCOPE (Manella et al., Nature Communication 2021). This methodology opens the door to a wide range of applications, in both basic and translational research. For example, it allows screening multiple drugs (in-use or newly developed) in parallel to identify which affects the clock and how – with high relevance to chrono-medicine. It also allows the experimental testing of different models of clock resetting quantitatively. Hence, it opens the door to a wide range of basic and translational research opportunities.

The relevant projects address the influence of circadian clocks on exercise performance, and training efficiency, as well as the effect of chronotype, feeding, and hypoxia on exercise capacity.

Circadian clocks are key regulators of daily physiology and metabolism in mammals. Our understanding of the role of the circadian clock and specific clock proteins in controlling exercise capacity is rudimentary. Consequently, there is growing interest in exercise biology in general, specifically in its interaction with other processes that govern whole-body physiology and metabolism. We have reported that mice show a day-time variance in exercise capacity, and it is affected by exercise intensity and clock proteins and elicits a distinct muscle transcriptomic and metabolic signature. Specifically, we demonstrated that ZMP, an AMPK activator, is induced by exercise in a daytime-dependent manner. We continue to study various aspects of exercise physiology through the lens of circadian biology (Ezagouri et al., Cell Metabolism, 2019; Adamovich et al., Proc. Natl. Acad. Sci., 2021.).

We employ various clock mutant mouse models with different light regimens to characterize the interaction between clocks and exercise. Further, we have designed and built fully automated time-controlled Running Wheels that can be programmed in advance to be in locked or unlocked positions for designated times to enable scheduled training of animals without manual interventions. This experimental setup is optimized for addressing questions regarding the involvement of daytime and circadian clocks in regulating exercise capacity (Adamovich et al., STAR Protocols, 2021).

We are also studying the molecular clock and skeletal muscle metabolism in health and disease.

Interdisciplinary collaboration between the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, and the Weizmann Institute of Science in Rehovot, Israel, we seek a highly motivated postdoctoral researcher to explore the regulatory interface between chronobiology and the RNA-based regulation (riboregulation) of key elements of the mammalian clock. This project will combine RNA biology, systems biology, mechanistic studies, and bioinformatics. The successful candidate will work at both EMBL and Weizmann under the mentorship of Prof. Matthias Hentze (EMBL) and Prof. Gad Asher (Weizmann). Please contact us informally as soon as possible because suitable candidates are expected to apply for the competitive EMBL EIPOD-LinC fellowship (https://www.embl.org/about/info/postdoctoral-programme/eipod-linc-explor...) by 18 January, 2023.