Nobel Prize for Physiology or Medicine – BiotechReality – Information Intelligence System for Biopharma

Two scientists, Victor Ambros and Gary Ruvkun have been recognised with this year's Nobel Prize for discovering a key idea regulating gene activity. Our chromosomes contain information equivalent to an instruction manual for every cell in our body. Every cell possesses identical chromosomes, hence every cell includes precisely the same collection of genes and exactly the same set of instructions. However, certain cell types such as nerve and muscle cells have distinctly different properties. How do these variations come about? Gene regulation, which enables each cell to choose just the pertinent instructions, holds the key to the solution. This guarantees that in every cell type, just the appropriate set of genes is activated. Gary Ruvkun and Victor Ambros were fascinated by the ways in which various cell types grow. They found microRNA, a novel class of minuscule RNA molecules that are essential for the control of gene expression. Their revolutionary finding unveiled a novel theory of gene control that proved to be crucial for all multicellular creatures, including humans. The human genome is known to code for more than a thousand microRNAs. Their startling discovery opened our understanding of gene control to a whole new level. It's becoming clear that microRNAs play a key role in the growth and operation of organisms. The discovery of a crucial regulatory mechanism that cells utilize to regulate gene activity is the main focus of this year's Nobel Prize. Transcription is the process by which genetic information moves from DNA to messenger RNA (mRNA), which is then transferred to the cellular machinery responsible for producing proteins. The genetic instructions contained in DNA are translated by mRNAs there, resulting in the production of proteins. Since the mid-20th century, some of the most significant scientific discoveries have described how these processes function. Thus, for many years, one of the main objectives has been to comprehend how gene activity is regulated. Numerous distinct cell types make up our organs and tissues, and each one has the same genetic information encoded in its DNA. These various cells do, however, express distinct protein sets. How is it possible? The exact control of gene activity to ensure that just the appropriate set of genes are activated in each distinct cell type holds the key to the solution. For instance, this makes it possible for intestine, muscular, and various kinds of neurone cells to carry out their specific tasks. Furthermore, in order to adjust cellular activities to shifting conditions in our bodies and surroundings, gene activity needs to be continuously adjusted. If gene regulation goes incorrect, it can lead to significant disorders such as cancer, diabetes, or autoimmune. Victor Ambros and Gary Ruvkun were postdoctoral researchers in the lab of Robert Horvitz, who shared the 2002 Nobel Prize with Sydney Brenner and John Sulston, in the late 1980s. They investigated C. elegans, a quite inconspicuous roundworm of 1 mm in length, in Horvitz's lab. Because C. elegans is a tiny creature, it may be used as a helpful model to study how tissues develop and mature in multicellular species. This is because it has numerous specialised cell types, including nerve and muscle cells, that are also seen in bigger, more complicated animals. Ambros and Ruvkun were interested in genes that regulate when distinct genetic programs are activated, allowing different cell types to grow at the appropriate times. Victor Ambros examined the lin-4 mutant in his newly formed laboratory at Harvard University following his postdoctoral studies. The gene could be cloned thanks to methodical mapping, which also produced an unexpected discovery. An very brief RNA molecule without a coding for protein synthesis was generated by the lin-4 gene. These unexpected findings showed that the inhibition of lin-14 was caused by this short RNA from lin-4. How could this function? Concurrently, Gary Ruvkun explored the control of the lin-14 gene at his newly established laboratory at Massachusetts General Hospital and Harvard Medical School. Ruvkun demonstrated that the inhibition of lin-4 does not occur through inhibition of mRNA synthesis from lin-14, contrary to the then-known mechanism of gene regulation. By stopping the synthesis of proteins, the regulation seemed to take place later in the process of gene expression. Additionally, a section of lin-14 mRNA that was required for lin-4 to block it was discovered through experiments. After comparing their research, the two laureates made a ground-breaking discovery. The crucial portion of the lin-14 mRNA had complementary sequences that the short lin-4 sequence matched. Additional research by Ambros and Ruvkun shown that the lin-4 microRNA inhibits lin-14 by attaching to complementary regions in its mRNA and preventing the synthesis of lin-14 protein. We had uncovered a novel concept of gene control, facilitated by a hitherto unidentified class of RNA known as microRNA! Two publications in the journal Cell presented the results in 1993. The scientific community originally responded to the reported data with nearly total silence. Despite the intriguing findings, the novel system of gene regulation was thought to be a trait unique to C. elegans and probably unimportant to humans and other more sophisticated species. When Ruvkun's research team revealed the identification of a different microRNA that is encoded by the let-7 gene in 2000, that perspective was altered. Unlike lin-4, the let-7 gene was substantially preserved and prevalent throughout the animal kingdom. Numerous microRNAs were discovered in the years that followed as a result of the article's intense attention. Today, we know that there are more than a thousand genes for various microRNAs in humans, and that gene control by microRNA is universal throughout multicellular species. Also, Read| Nobel Prize 2023 in Medicine for the scientists behind mRNA COVID-19 vaccines Apart from the identification of novel microRNAs, investigations conducted by many research teams clarified the processes involved in the synthesis and delivery of microRNAs to complementary target regions in regulated mRNAs. MicroRNA binding results in either mRNA breakdown or the suppression of protein synthesis. It's interesting to note that a single microRNA may control the expression of several distinct genes, and that multiple microRNAs can control the expression of a single gene, coordinating and fine-tuning whole gene networks. The process of microRNA-mediated gene regulation dates back hundreds of millions of years, as initially reported by Ambros and Ruvkun. The evolution of increasingly sophisticated animals has been made possible by this technique. Genetic research has shown us that the absence of microRNAs impairs the proper development of cells and tissues. Mutations in the genes encoding for microRNAs have been discovered in humans, leading to diseases such congenital hearing loss, skeletal and ocular abnormalities, and cancer. Aberrant control by microRNA can also contribute to cancer. The DICER1 syndrome, an uncommon but serious condition associated with cancer in a number of organs and tissues, is caused by mutations in one of the proteins necessary for the synthesis of microRNA. Journal References Lee, R C et al. “The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14.” Cell vol. 75,5 (1993): 843-54. DOI:10.1016/0092-8674(93)90529-y. Wightman, B et al. “Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans.” Cell vol. 75,5 (1993): 855-62. DOI:10.1016/0092-8674(93)90530-4. Pasquinelli, A E et al. “Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA.” Nature vol. 408,6808 (2000): 86-9. DOI:10.1038/35040556. Last Modified:

Tag: Nobel Prize for Physiology or Medicine

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