PhD positions

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Membrane proteins make up a quarter of the proteome of every living organism and participate in nearly every biological process. We are interested in the fascinating process of how these proteins get produced, fold, and assemble in cells. The questions we address are: How do proteins fold in the membranes of living cells? How do the dynamic features of unfolded proteins assist in this process? How do cellular factors recognize membrane proteins that failed to fold and need to be cleared? The lab combines biochemical, cell biology, genetic and computational tools. For more details, visit http://www.weizmann.ac.il/Biomolecular_Sciences/Fluman  

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.

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.

Mitochondria are essential for the function of the eukaryotic cell- why?

Over the past two decades it has become apparent that a core and ubiquitous function of mitochondria is iron-sulfur (Fe-S) cluster biosynthesis. These ancient co-factors, which are produced in the mitochondria, are vital for proteins that take part in DNA replication, translation, metabolism and cellular respiration. In light of these essential tasks, it's not surprising that problems in Fe-S cluster synthesis are linked to human diseases, including the most common mitochondrial disease- Friedreich's ataxia. Yet surprisingly little is known about this pathway, and how it is regulated by the cell is even more mysterious. 

Our lab couples cutting edge genetic and high content tools with cell biology and biochemistry approaches to shed new light on this essential pathway and how it's wired into the human cell. 

To learn more, visit: https://www.astlabweizmann.com/

To hear Tslil talking about our science, visit: https://www.youtube.com/watch?v=H4u6p8WmzvE&t=17s

Regulation of gene expression at the transcriptional and translational levels is fundamental to all biological activities and is frequently altered in disease states. Our broad research interests are (i) to elucidate how the transcription and translation processes control the cellular response to environmental stimuli; (ii) to reveal the connections between the transcription and translation processes and (iii) to develop tools to manipulate these processes for the potential treatment of cancer, chronic inflammation and neurodegenerative diseases.