Monday, October 3, 2016

Man and yeast: Nobel laureate in medicine, proved of the universal “self-blame” – Вести.Ru

the Nobel Committee today announced the winner of the 2016 awards in physiology and medicine. They became a Japanese scientist, molecular biologist, asinari Osumi Tokyo Institute of technology. The prize was awarded for his discoveries in the field of autophagy.

In a statement, the Nobel Committee noted that, opened and discovered the mechanisms underlying autophagy, the fundamental process of destruction and recycling of cellular components”. The word “autophagy” is derived from two Greek words “auto” meaning “self” and “phagein” meaning “to eat”. Thus, it literally means “samopouzdanje” (loosely translated “self-blame”).

Autophagy has been known for over 50 years, but its fundamental importance for physiology and medicine was recognized only after the studies, conducted in the 1990-ies. It is through these works he received the Nobel prize.

a General understanding of the autophagy came from scientists in the 1960s, when researchers first observed how cells destroy their own content using the conclusion of the last in the membrane. In this process, the formed vesicles similar to pouches of education, which are then delivered in a “compartment” of processing in the cell called the lysosome) for disposal.

But because of the lack of information made it difficult to study the characteristics of this phenomenon. Osumi conducted a series of brilliant experiments in the early 1990-ies. In particular, the researchers used Baker’s yeast to identify the genes that determine the process of autophagy. Then the researcher began to identify the mechanisms underlying the samopoedaniya in yeast and demonstrated that such complex mechanisms are used in human cells.

the Discovery, has led to a new paradigm in the understanding by scientists of how cells recycle their contents. His discovery helped pave the way to understanding the fundamental importance of autophagy in many physiological processes such as adaptation to starvation.

Mutations of genes that control the process of autophagy, can cause disease. In addition, the process of autophagy is an important component of cancer and neurological diseases.

Tell us a bit about the history, without which there would be the opening. In the mid-1950s years, scientists have identified a new specialized cellular compartment, organelle that contains enzymes that metabolize proteins, carbohydrates and fats. The organelle called the lysosome and defined its functions (workstation for the destruction of cellular components).

By the way, Belgian scientist Christian de Dyuv was awarded the Nobel prize in physiology or medicine in 1974 for his discovery of the lysosomes.

the New observations in the 1960-ies showed that a large number of cellular components and even whole organelles can sometimes be found inside the lysosomes.

Turns out, the cells possess a strategy for the delivery of large “cargo” in lysosomes. Further biokhimicheskie and microscopic studies revealed a new type of vesicles transporting such cellular cargo to lysosomes for destruction. Christian de Dyuv coined the term autophagy, “samopouzdanje” to describe this process. A new type of vesicles were identified autolysosome (or autophagosome).

during the 1970s and 1980s, researchers focused on the explanation of the operation of another system used for destruction of proteins –the proteasome.In the context of this topic, Aaron Ciechanover, Avram, Hershko and Irwin rose were awarded the Nobel prize 2004 in chemistry for “the discovery of the role of ubiquitin in the cellular system of protein degradation in proteasomes”. Proteasome effectively destroy proteins “one by one”, but this mechanism does not explain how cells get rid of large protein complexes and “worn out” organelles.

Japanese scientist, actively participated in various studies, but when running our own laboratory in 1998, he focused on the study of the destruction of proteins in the yeast vacuole — the organelle that functions in human cells performed by the lysosome. Yeast cells are relatively simple to study and therefore are often used as models for human cells. They are particularly useful to identify genes that play an important role in complex cellular processes.

But, faced with a serious problem – the yeast cells are small and their internal structure is not so easy to distinguish under a microscope. The scientist even had doubts whether in this case autophagy. The researcher felt that if he can stop the process of destruction of the material in the vacuoles, autophagy is present – then autolysosome will have to accumulate inside vacuoles and become visible under the microscope.

the Scientist was culturing the mutated yeast vacuolar degradation losses and at the same time they stimulated autophagy, causing the cells to starve. And the results were striking. Within a few hours vacuoles filled with small vesicles, which have not yet been destroyed. Vesicles were autolysosome, and the experiment scientist have proven that autophagy exist in yeast cells. But more importantly – now the scientist got a way to identify and characterize key genes involved in this process. This revolutionary study was published over 20 years ago in 1992.

Later Osumi used his modified yeast strains in which autolysosome accumulated during starvation. This accumulation should not occur if the genes responsible for autophagy, was have been inactivated. Osumi processed yeast cells is a chemical that is selectively introduced mutations in many genes, and then he stimulated autophagy. His strategy worked.

Osumi revealed the first genes required for autophagy. In subsequent experiments, scientists have been functionally characterized proteins, encoded by these genes. The results of the research have shown that autophagy is controlled by a cascade of proteins and protein complexes, each of which governs a separate phase, such as nucleation or the formation of autolysosome.

After determining the mechanism of autophagy in yeast still remains one outstanding question: is there an appropriate mechanism to control this process in other organisms? It soon became clear that almost identical processes occur in human cells. Now, scientists have access to the tools needed to explore the importance of autophagy in the human body.

And thanks Osumi and his followers today, the world knows that autophagy controls important physiological functions, in which cell components should be recycled or destroyed.

Autophagy can quickly provide the “fuel” and building blocks for the cell update components. Therefore, the process is important for the cellular response to starvation and other types of stress. In addition, during infection, autophagy assists to stop the introduction of intracellular bacteria and viruses.

Autophagy also contributes to embryonic development and cellular differentiation. Cells also use autophagy to eliminate damaged proteins and organelles — this mechanism of “quality control” is crucial to combating the negative effects of aging.

by the Way, a violation of the processes of autophagy are also associated with Parkinson’s disease, type II diabetes and other diseases that typically appear in old age.

Mutations of genes important for autophagy, can be caused by a genetic disease, the mechanisms of autophagy is associated with cancer. Today, there are numerous studies on the development of drugs intended for the stimulation of autophagy in various diseases.

Recall that today, October 3, in Stockholm, started the Nobel week. According to tradition, its beginning marked the announcement of the prize winners in physiology and medicine.

And last year the Nobel prize in medicine scientist brought parasitic worms.


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