Available Positions

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.

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 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.

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.

• 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.

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 enviromental stimuli; (ii) to reveal the connections between the transcription and translation processes and (iii) to develop tools to manipulate these processes for potential treatment of cancer, chronic inflammation and neurodegenrative diseases.

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 enviromental stimuli; (ii) to reveal the connections between the transcription and translation processes and (iii) to develop tools to manipulate these processes for potential treatment of cancer, chronic inflammation and neurodegenrative diseases.

In our research, we focus on the following aspects of beta cell function:

1. The transcriptional mechanisms underlying the normal embryonic development of beta cells and the functioning of mature beta cells
2. Manipulating pancreatic cellular identity: molecular mechanisms controlling exocrine to endocrine cell reprogramming
3. Dissecting the signaling mechanism that permit  beta cells to respond to modulators of insulin secretion, in particular long chain and short chain fatty acids

See:

https://www.weizmann.ac.il/Biomolecular_Sciences/Walker/

In our research, we focus on the following aspects of beta cell function:

1. The transcriptional mechanisms underlying the normal embryonic development of beta cells and the functioning of mature beta cells
2. Manipulating pancreatic cellular identity: molecular mechanisms controlling exocrine to endocrine cell reprogramming
3. Dissecting the signaling mechanism that permit  beta cells to respond to modulators of insulin secretion, in particular long chain and short chain fatty acids

See:

https://www.weizmann.ac.il/Biomolecular_Sciences/Walker/

Motivated and creative students with background in molecular biology are invited to join our studies of the mechanisms by which signaling by the TNF family contributes to immune defense, to chronic inflammatory and autoimmune diseases and to cancer, and our attempts to derive from this knowledge new ways of therapy. See our website and list of publications for the range of research subjects that we are exploring and for the range of experimental approaches that we are applying. (https://www.weizmann.ac.il/Biomolecular_Sciences/Wallach/home)

Caspase-8, a cysteine protease discovered in our laboratory, is the main proximal signaling enzyme in the activation of the extrinsic cell-death pathway by receptors of the TNF/NGF family. In certain cells it also participates in the regulation of cell growth, differentiation and survival. A number of different human tumors, including small cell lung carcinoma, neuroblastoma, hepatocellular carcinoma, and others, are frequently deficient of caspase-8. This deficiency occurs by several different mechanisms, indicating that it is not a consequence of the oncogenic transformation but is rather causal to it. Applying molecular approaches, cell-culture and animal models we explore the mechanisms accounting for the tumor suppressor role of caspase-8 and the functional consequences of its deletion in cancer cells.

Transgenic and conditional-knockout mouse models are applied to gain better knowledge of the physiological and pathophysiological function of the following signaling proteins that were discovered in our laboratory: (a) Caspase-8, a cysteine protease that we have initially found to serve as the main proximal signaling protein in the initiation of death induction by the receptors (the extrinsic cell-death pathway), yet has more recently found also to serve various non-apoptotic roles. We are mainly interested in further exploring its function in the cross-talk between the epidermal and dermal layers of the skin, in the liver, and in the insulin-producing beta Langerhans cells. (b) NIK, a protein kinase (a MAP3K) that signals for activation of transcription factors of the NF kappa B family, specifically by receptors that, through activation of NF kappa B, control adaptive immunity and lymph-node generation. (c) CYLD, a deubiquitination enzyme that acts specifically to reverse K63-linked ubiquitination and thus serves to arrest initiation of several signaling cascades. (d) IREN, a member of the sorting-nexins family that mediates trafficking of signaling proteins activated by the receptors of the TNF/NGF family.

The Yaron lab studies the regulation of neuronal wiring

• The mechanisms of axonal guidance and pruning.
• The interplay between genetics and experience.

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  

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  

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  

See short description 

See short description 

OPEN PhD and Post-Doc positions: Applicants with a strong research background at the intersection of molecular biology, biochemistry, imaging and/or biophysics are encouraged to apply. Experience in microbiology, molecular genetics (including CRISPR/Cas9), advanced imaging platforms (including image analysis) or advanced protein chemistry is advantageous. This is a full-time position available from June 2022 for a period of two years with a possibility of a further extension subject to funding availability. Candidate should send a cover letter and CV (includes a publication list) to Dr. Neta Regev-Rudzki. For any informal inquiries please contact us by email at neta.regev-rudzki@weizmann.ac.il