micro-macro

Institute scientists have discovered a protein that works in the brain and contributes to weight gain and obesity, by increasing resistance to leptin 

"And the water came and put out the fire
that burned the stick
He punched the dog that bit the cat
devour the goat that our father brought"

Had Gadiya - from the Passover Haggadah

A sequence of events in the spirit of "Had-Gadia" from the Passover Haggadah occurs every day in many biological control systems. Dr. Eran Hornstein, from the department of molecular genetics at the Weizmann Institute of Science, describes in this way a new pathway for controlling gene expression in the pancreas: microRNA molecules came and suppressed the expression of a negative transcription factor, which inhibited the gene that codes for insulin, which regulates the levels of the sugar in the body.

At the focus of Dr. Hornstein's research is one of the players in this sequence of events: microRNA. These are very short sequences of genetic material, which do not code for making a protein. Instead, they take part in regulating a wide range of activities that occur in the cell, and are therefore also involved in several diseases. In a series of experiments, Dr. Hornstein and the members of his research group examined the role played by microRNA molecules in the beta cells of the pancreas - these are the cells that produce the hormone insulin, and are therefore responsible for regulating sugar levels in the body. Poor activity of the beta cells causes an increase in blood sugar levels, and diabetes.

The findings, recently published in the scientific journal EMBO Journal, shed new light on the control of insulin production, and may even help, in the future, in the diagnosis and treatment of diabetes. The research team included postdoctoral researcher Dr. Tali Melkman-Zahavi, research students Sharon Cardo-Russo, Roni Oren, Amitai Mandelbaum and Tirosh Shapira, and laboratory technician Natalie Rivkin. In the first step, the team of scientists wanted to check whether microRNA molecules play any role in the activity of the pancreas. Through the use of advanced genetic methods, which make it possible to prevent the formation of microRNA in the pancreas of a mouse, they were able to get a clear answer: without microRNA, the mouse is unable to produce insulin, and as a result quickly develops symptoms of diabetes.

To better understand the role of microRNA, the scientists examined the process in which the hormone insulin is produced based on the information encoded in the insulin gene, and looked for the stage whose existence depends on the presence of microRNA. It turned out that this is the transcription stage - the stage where the genetic information found in DNA is transformed into a messenger RNA molecule. This discovery raised a new question. "The involvement of microRNA in the regulation of the transcription phase of insulin was not expected, because usually these molecules intervene at later stages in the control of the expression from a shield to a protein," says Dr. Hornstein. "To try to reconcile this contradiction, we hypothesized that another mediating factor is involved in the process - a negative transcription factor."

All the cells in our body carry the genetic information necessary to produce insulin, but only the beta cells in the pancreas actually produce the hormone. One of the reasons for this is that other cells actively suppress the transcription of the gene that codes for insulin using negative transcription factors. The beta cells, on the other hand, contain an abundance of positive transcription factors, which bind to the insulin gene and initiate the transcription process, and only a small amount of negative transcription factors, which inhibit the process. Additional experiments performed by the scientists showed that the microRNAs have a targeted effect on the negative transcription factors in the beta cells, and suppress their expression so that insulin production is not disturbed. The scientists were able to identify four particular microRNA molecules that stimulate insulin production in this way.

These findings, which explain the role played by microRNA molecules in insulin production, add another layer to our understanding of the mechanisms involved in diabetes. It is possible that this understanding will lead, in the future, to improving the ability to diagnose the disease and treat it.

watching movies
Dr. Eran Hornstein recommends the movie "The Butterfly and the Diving Bell": "The movie is about the French journalist Jean-Dominique Bauby, whose fast and juicy life as the editor of the monthly 'El' comes to a screeching halt when he suffers a stroke. Baubi becomes imprisoned inside his body: he is cognitively preserved, but only his left eyelid allows him to communicate with the world. Thus, each sentence becomes a slow and tedious task. In the blinks of Baubi's left eye, letter is added to letter, and words are slowly woven into an intimate and moving autobiography. Director Julian Schnabel turned the story into a work of added value about our fragility and the victory of the spirit over the sick body, not to mention redemption. The cinematography of the film is interspersed with broken images and spots of light, which allow a glimpse into Baubi's fragility. At the same time, we are also given the opportunity to experience his consciousness with the help of the same artistic means: this is how the viewer experiences the confusion of exterior and interior, present-past, reality and imagination. The film is exciting, but does not fall into potential melodramatic traps. The combination of the excellent direction, cinematography and acting make it one of the best I've seen recently."