Nobel Prize in Physiology or Medicine and C. elegans

1. In October 2024, the Nobel Prize for Medicine was awarded to Victor Ambros and Gary Ruvkun for their discovery of microRNA, tiny molecules that play a big role in controlling gene activity.
2. This discovery has helped scientists to understand how genes work and how complex organisms, like humans, develop.
3. The Nobel Committee recognized Ambros and Ruvkun for finding a key process that regulates gene activity, which has been crucial for the evolution of life over millions of years.
4. MicroRNAs are a critical part of gene regulation, shedding light on how cells function in many organisms, including humans.

Why Did Ambros and Ruvkun Study MicroRNA?

1. Ambros and Ruvkun were awarded for discovering how genes are controlled.
2. Imagine chromosomes, which hold genetic information in DNA, as a large toolbox.
3. Every cell in the body has the same toolbox with the same set of tools (or genes).
4. But different cells need to use different tools depending on their job.
   1. For example, a nerve cell might use a tool to send signals, while a muscle cell might use a tool to help with movement.
5. This is possible through gene regulation, a process that makes sure only the right set of genes is used in each type of cell.
6. Ambros and Ruvkun wanted to understand how this gene regulation works, leading to their discovery of microRNA, which changed how scientists view gene control in complex organisms like humans.

Why is Gene Regulation Important?

1. Genes in DNA are copied into a molecule called mRNA, which carries instructions for making proteins.
2. These proteins carry out essential tasks in the body, like helping muscles move or nerves send signals.
3. Different cells in the body make different proteins depending on what they need to do.
4. Gene regulation controls which genes are turned on or off in each cell, helping it carry out its specific function.
5. Problems in gene regulation can lead to serious diseases like cancer, diabetes, or autoimmune disorders.
6. Understanding how genes are regulated could help us understand and treat these conditions.
7. In the 1960s, scientists discovered that certain proteins, called transcription factors, could control gene activity by binding to specific parts of DNA.
8. These transcription factors acted like switches, turning genes on or off depending on the needs of the cell.
9. However, in 1993, Ambros and Ruvkun made a surprising discovery that added a new layer to gene regulation: microRNA.
10. This tiny molecule could also control genes, but in a way no one expected.

How Was MicroRNA Discovered?

1. In the late 1980s, Ambros and Ruvkun were studying a tiny roundworm called Caenorhabditis elegans (C. elegans), which is just 1 millimeter long but has many of the same types of cells as larger animals.
2. This made it an ideal model for studying how cells and tissues develop.
3. The scientists focused on two genes in C. elegans, called lin-4 and lin-14, which control when cells mature.
4. They noticed that certain mutant worms had problems with this timing.
   1. In simple words, certain Mutant worms had issues with the normal timing of when their cells should mature, which helped lead to the discovery of how certain genes (like lin-4) regulate this process.
5. Ambros found that lin-4 seemed to stop lin-14 from working, but the exact mechanism was unclear.
6. Ambros discovered that lin-4 produced a tiny RNA molecule that didn’t make proteins like most genes, but instead blocked lin-14 from working.
7. Meanwhile, Ruvkun found that lin-4 was not stopping the production of lin-14’s mRNA, but rather preventing it from making the protein.
8. As they compared their findings, they realized that the small RNA from lin-4 could bind to a part of lin-14’s mRNA, shutting down its protein production.
9. This was a completely new way of controlling genes, using tiny RNA molecules that were later named microRNAs.
10. At first, this discovery was not widely recognized, as scientists believed it was unique to C. elegans.
11. But in 2000, Ruvkun's team discovered another microRNA, called let-7, in many species, including humans.
12. This opened the door to finding hundreds of other microRNAs, and today we know they play a key role in regulating genes in almost all multicellular organisms, including humans.

Caenorhabditis elegans (C. ELEGANS) Simple microscopic worms, studying which has won scientists four Nobel Prizes so far C. elegans is a nematode worm, which is part of a large group of worms called Nematoda. Nematodes are among the most common animals on Earth. They are found in many places, including soil, freshwater, oceans, and even in extreme environments (like deep cracks in the Earth). Some live freely, while others are parasites that can harm plants and animals. Nematodes have smooth skin, are not divided into segments, and have a long, tube-like shape that narrows at both ends. They can live on land or in water. It grows from a fertilized egg into a one-millimeter-long adult in just 3-5 days. C. elegans has two sexes: a hermaphrodite (which can reproduce by itself) and a male. The worm's body is mainly a tube-like structure that includes an outer layer (called a cuticle), a mouth (pharynx), a gut, and a reproductive system. It ages over time, losing strength and eventually dying. Studying these processes helps scientists understand genetics and behavior. C. elegans was the first multicellular organism to have its entire genome sequenced (the complete set of its genes) and its nerve connections mapped. It is widely used to study how nerves work and cell biology. This research has led to important discoveries about health and disease. Four Nobels The 1-millimeter nematode (C. elegans) has helped scientists understand how healthy cells are instructed to kill themselves and how the process goes awry in AIDS, strokes, and degenerative diseases. (That work was the subject of the 2002 Nobel Prize in physiology or medicine.) Self-proclaimed “worm people” were recognised by the Nobel committee in 2006 for discovering gene silencing, which became the basis for an entirely new class of drugs. Two years later, the chemistry prize went to scientists who used nematodes to help invent cellular “lanterns” to see the inner workings of a cell. For each prize, a laureate made sure to thank the worm for its contributions, though perhaps the most famous nod came from Sydney Brenner, who won the first “worm Nobel.” Without doubt, the fourth winner of the Nobel Prize this year is Caenorhabditis elegans.

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