MSc rotation

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.

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.

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 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/