Today (Monday) the Karolinska Institute in Sweden announced the winners of the Nobel Prize in Medicine and Physiology for 2023. The prize committee decided that the winners are the researchers Victor Ambrose and Gary Robkon for the discovery of “micro RNA and its role in gene regulation in the cell nucleus”. The winners will receive a prize worth 10 million kroner, which is about 900 thousand dollars, which will be awarded to them at a ceremony to be held in Stockholm this December.
The information stored within our chromosomes can be compared to an instruction manual for all the cells in our body. Each cell contains the same chromosomes, so each cell contains exactly the same set of genes and exactly the same set of instructions. However, different cell types, such as muscle cells and nerve cells, have very distinct characteristics. How do these differences arise? The answer lies in gene regulation, which allows each cell to choose only the relevant instructions. This ensures that only the correct set of genes are active in each cell type.
Victor Ambrose and Gary Rubcon were interested in how different types of cells develop. They discovered microRNAs, a new class of tiny RNA molecules that play a crucial role in gene regulation. Their groundbreaking discovery revealed an entirely new principle of gene regulation that turned out to be essential to multicellular organisms, including humans. It is now known that the human genome encodes more than a thousand microRNAs. Their surprising discovery revealed an entirely new dimension to gene regulation. MicroRNA is proving to be fundamentally important to how organisms develop and function.
This year’s Nobel Prize focuses on the discovery of an essential regulatory mechanism used in cells to control gene activity. Genetic information flows from DNA to messenger RNA (mRNA), through a process called transcription, and then to the cellular machinery for protein production. There, mRNA is translated so that proteins are produced according to the genetic instructions stored in DNA. Since the mid-20th century, some of the most basic scientific discoveries have explained how these processes work.
Our organs and tissues are made up of many different types of cells, all with the same genetic information stored in their DNA. However, these different cells express unique sets of proteins. How is that possible? The answer lies in the precise regulation of gene activity so that only the correct set of genes are active in each specific cell type.
This allows, for example, muscle cells, intestinal cells and different types of nerve cells to carry out their specialized functions. In addition, gene activity must be constantly adjusted to adapt cellular functions to the changing conditions in our body and environment. If gene regulation goes wrong, it can lead to serious diseases such as cancer, diabetes or autoimmunity. Therefore, understanding the regulation of gene activity has been an important goal for many decades.
The results that the two made about the mRNA regulation mechanism in the body’s cells were initially ignored by the medical community. This perception changed in 2000 when Rubcon’s research group published their discovery of another microRNA, which is present in all animal species. The article generated a lot of interest, and over the next few years hundreds of different microRNAs were identified. Today, we know that there are more than a thousand different microRNA genes in humans, and that gene regulation by microRNAs is universal among multicellular organisms. .
Gene regulation by microRNA, first discovered by Ambrose and Rubcon, has been operating for hundreds of millions of years. This mechanism allowed the development of increasingly complex organisms. It is known from genetic research that cells and tissues do not develop normally without microRNA. Abnormal regulation by microRNAs can contribute to cancer, and mutations in genes encoding microRNAs have been found in humans, causing conditions such as congenital hearing loss, eye and skeletal disorders.
Mutations in one of the proteins required for microRNA production cause DICER1 syndrome, a rare but serious syndrome associated with cancer in various organs and tissues. The discovery of the two may lead to early diagnosis or the development of new genetic treatments for incurable diseases.
The previous wins
The Nobel Prize was awarded last year to researchers Prof. Kathleen Crico and Prof. Drew Weissman for their discovery of components in the hereditary material modifications that led to the development of mRNA vaccines for Corona.
A year earlier, the award was given to the Swedish researcher Dr. Sveta Pabo for being able to create a sequence of DNA from the bones of animals that became extinct 30 thousand years ago and comparing it to that of humans. This was a breakthrough because he estimated that in history there was a mixing of the species, even though they lived for hundreds of thousands of years at different ends of the earth. The mixing of the species after migrations on Earth, made it possible to prolong their survival in difficult conditions.
The Nobel Prize for Medicine was awarded a year earlier to Dr. David Julius, an American physiologist, and the neurobiologist Dr. Erdem Patfotian, for their discovery of temperature and touch receptors. These receptors remained unknown all these years, until the winners were discovered. For example, when we eat spicy food, we start to sweat, and the brain thinks that there is a change in body temperature. It was known that the substance capsaicin is involved in the sensation of spicy taste and the body’s reaction to it.
In 2020, the Nobel Prize for Medicine was awarded to Harvey G. Alter, Michael Upton and Charles Rice for the discovery of the hepatitis C virus. The World Health Organization estimates that there are over 70 million hepatitis C cases in the world and many more cases are undiagnosed. The disease causes 400,000 deaths per year in the world and is a major factor in the need for transplantation.
In 2019, William Kaelin from Harvard University, Sir Peter Ratcliffe from Oxford University and Greg Semenza from Johns Hopkins University won the prize, for their discovery of the sensing processes of oxygen levels among the cells necessary for the existence of life. Their work investigating how cells adapt to oxygen levels is relevant to conditions such as pregnancy, altitude sickness, cancer and wound healing.
In 2018, the Nobel Prize was awarded to James P. Alison and Tsuko Honjo for developing innovative cancer treatments that allow the immune system to destroy cancerous tumors. Their research led to the development of drugs for skin, lung and kidney cancers.