Nobel Prize
2006 Nobel Prize in Chemistry
The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry for 2006 to
Roger D. Kornberg of Stanford University "for his studies of the molecular basis of eukaryotic transcription".
In order for our bodies to make use of the information stored in the genes, a copy must first be made and transferred to the outer parts of the cells. There it is used as an instruction for protein production – it is the proteins that in their turn actually construct the organism and its function. The copying process is called transcription. Roger Kornberg was the first to create an actual picture of how transcription works at a molecular level in the important group of organisms called eukaryotes (organisms whose cells have a well-defined nucleus). Mammals like ourselves are included in this group, as is ordinary yeast.
Transcription is necessary for all life. This makes the detailed description of the mechanism that Roger Kornberg provides exactly the kind of "most important chemical discovery" referred to by Alfred Nobel in his will.
If transcription stops, genetic information is no longer transferred into the different parts of the body. Since these are then no longer renewed, the organism dies within a few days. This is what happens in cases of poisoning by certain toadstools, like the death cap, since the toxin stops the transcription process. Understanding of how transcription works also has a fundamental medical importance. Disturbances in the transcription process are involved in many human illnesses such as cancer, heart disease and various kinds of inflammation.
The capacity of stem cells to develop into different types of specific cells with well-defined functions in different organs, is also linked to how the transcription is regulated. Understanding more about the transcription process is therefore important for the development of different therapeutic applications of stem cells.
In 1959, the then twelve-year-old Roger Kornberg came to Stockholm to see his father, Arthur Kornberg, receive the Nobel Prize in Physiology or Medicine for his studies of how genetic information is transferred from one DNA-molecule to another. Kornberg senior had described how genetic information is transferred from a mother cell to its daughters. What Roger Kornberg himself has now done is to describe how the genetic information is copied from DNA into what is called messenger-RNA. The messenger-RNA carries the information out of the cell nucleus so that it can be used to construct the proteins.
Kornberg's contribution has culminated in his creation of detailed crystallographic pictures describing the transcription apparatus in full action in a eukaryotic cell. In his pictures (all of them created since 2000) we can see the new RNA-strand gradually developing, as well as the role of several other molecules necessary for the transcription process. The pictures are so detailed that separate atoms can be distinguished and this makes it possible to understand the mechanisms of transcription and how it is regulated.
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2006 Nobel Prize in Physics
The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Physics for 2006 jointly to John C. Mather of the NASA Goddard Space Flight Center in Greenbelt, Maryland and George F. Smoot of the University of California, Berkeley "for their discovery of the blackbody form and anisotropy of the cosmic microwave background radiation".
This year the Physics Prize is awarded for work that looks back into the infancy of the Universe and attempts to gain some understanding of the origin of galaxies and stars. It is based on measurements made with the help of the COBE satellite launched by NASA in 1989.
The COBE results provided increased support for the Big Bang scenario for the origin of the Universe, as this is the only scenario that predicts the kind of cosmic microwave background radiation measured by COBE. These measurements also marked the inception of cosmology as a precise science. It was not long before it was followed up, for instance by the WMAP satellite, which yielded even clearer images of the background radiation. Very soon the European Planck satellite will be launched in order to study the radiation in even greater detail.
According to the Big Bang scenario, the cosmic microwave background radiation is a relic of the earliest phase of the Universe. Immediately after the big bang itself, the Universe can be compared to a glowing "body emitting radiation in which the distribution across different wavelengths depends solely on its temperature. The shape of the spectrum of this kind of radiation has a special form known as blackbody radiation. When it was emitted the temperature of the Universe was almost 3,000 degrees Centigrade. Since then, according to the Big Bang scenario, the radiation has gradually cooled as the Universe has expanded. The background radiation we can measure today corresponds to a temperature that is barely 2.7 degrees above absolute zero. The Laureates were able to calculate this temperature thanks to the blackbody spectrum revealed by the COBE measurements.
COBE also had the task of seeking small variations of temperature in different directions (which is what the term 'anisotropy' refers to). Extremely small differences of this kind in the temperature of the cosmic background radiation – in the range of a hundred-thousandth of a degree – offer an important clue to how the galaxies came into being. The variations in temperature show us how the matter in the Universe began to "aggregate". This was necessary if the galaxies, stars and ultimately life like us were to be able to develop. Without this mechanism matter would have taken a completely different form, spread evenly throughout the Universe.
COBE was launched using its own rocket on 18 November 1989. The first results were received after nine minutes of observations: COBE had registered a perfect blackbody spectrum. When the curve was later shown at an astronomy conference the results received a standing ovation.
The success of COBE was the outcome of prodigious team work involving more than 1,000 researchers, engineers and other participants. John Mather coordinated the entire process and also had primary responsibility for the experiment that revealed the blackbody form of the microwave background radiation measured by COBE. George Smoot had main responsibility for measuring the small variations in the temperature of the radiation.
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2006 Nobel Prize in Physiology or Medicine
The Nobel Assembly at Karolinska Institutet has awarded The Nobel Prize in Physiology or Medicine for 2006 jointly to Andrew Z. Fire of Stanford University and Craig C. Mello of the University of Massachusetts Medical School for their discovery of "RNA interference – gene silencing by double-stranded RNA".
This year's Nobel Laureates have discovered a fundamental mechanism for controlling the flow of genetic information. Our genome operates by sending instructions for the manufacture of proteins from DNA in the nucleus of the cell to the protein synthesizing machinery in the cytoplasm. These instructions are conveyed by messenger RNA (mRNA). In 1998, the American scientists Andrew Fire and Craig Mello published their discovery of a mechanism that can degrade mRNA from a specific gene. This mechanism, RNA interference, is activated when RNA molecules occur as double-stranded pairs in the cell. Double-stranded RNA activates biochemical machinery which degrades those mRNA molecules that carry a genetic code identical to that of the double-stranded RNA. When such mRNA molecules disappear, the corresponding gene is silenced and no protein of the encoded type is made.
RNA interference occurs in plants, animals, and humans. It is of great importance for the regulation of gene expression, participates in defense against viral infections, and keeps jumping genes under control. RNA interference is already being widely used in basic science as a method to study the function of genes and it may lead to novel therapies in the future.
The genetic code in DNA determines how proteins are built. The instructions contained in the DNA are copied to mRNA and subsequently used to synthesize proteins. This flow of genetic information from DNA via mRNA to protein has been termed the central dogma of molecular biology by the British Nobel Laureate Francis Crick. Proteins are involved in all processes of life, for instance as enzymes digesting our food, receptors receiving signals in the brain, and as antibodies defending us against bacteria.
Our genome consists of approximately 30,000 genes. However, only a fraction of them are used in each cell. Which genes are expressed (i.e. govern the synthesis of new proteins) is controlled by the machinery that copies DNA to mRNA in a process called transcription. It, in turn, can be modulated by various factors. The fundamental principles for the regulation of gene expression were identified more than 40 years ago by the French Nobel Laureates François Jacob and Jacques Monod. Today, we know that similar principles operate throughout evolution, from bacteria to humans. They also form the basis for gene technology, in which a DNA sequence is introduced into a cell to produce new protein.
Around 1990, molecular biologists obtained a number of unexpected results that were difficult to explain. The most striking effects were observed by plant biologists who were trying to increase the color intensity of the petals in petunias by introducing a gene inducing the formation of red pigment in the flowers. But instead of intensifying the colour, this treatment led to a complete loss of color and the petals turned white! The mechanism causing these effects remained enigmatic until Fire and Mello made the discovery for which they receive this year's Nobel Prize.
Andrew Fire and Craig Mello were investigating how gene expression is regulated in the nematode worm Caenorhabditis elegans. Injecting mRNA molecules encoding a muscle protein led to no changes in the behaviour of the worms. The genetic code in mRNA is described as being the 'sense' sequence, and injecting 'antisense' RNA, which can pair with the mRNA, also had no effect. But when Fire and Mello injected sense and antisense RNA together, they observed that the worms displayed peculiar, twitching movements. Similar movements were seen in worms that completely lacked a functioning gene for the muscle protein. What had happened?
When sense and antisense RNA molecules meet, they bind to each other and form double-stranded RNA. Could it be that such a double-stranded RNA molecule silences the gene carrying the same code as this particular RNA? Fire and Mello tested this hypothesis by injecting double-stranded RNA molecules containing the genetic codes for several other worm proteins. In every experiment, injection of double-stranded RNA carrying a genetic code led to silencing of the gene containing that particular code. The protein encoded by that gene was no longer formed.
After a series of simple but elegant experiments, Fire and Mello deduced that double-stranded RNA can silence genes, that this RNA interference is specific for the gene whose code matches that of the injected RNA molecule, and that RNA interference can spread between cells and even be inherited. It was enough to inject tiny amounts of double-stranded RNA to achieve an effect, and Fire and Mello therefore proposed that RNA interference (now commonly abbreviated to RNAi) is a catalytic process.
Fire and Mello published their findings in the journal Nature on February 19, 1998. Their discovery clarified many confusing and contradictory experimental observations and revealed a natural mechanism for controlling the flow of genetic information. This heralded the start of a new research field.
The components of the RNAi machinery were identified during the following years. Double-stranded RNA binds to a protein complex, Dicer, which cleaves it into fragments. Another protein complex, RISC, binds these fragments. One of the RNA strands is eliminated but the other remains bound to the RISC complex and serves as a probe to detect mRNA molecules. When an mRNA molecule can pair with the RNA fragment on RISC, it is bound to the RISC complex, cleaved and degraded. The gene served by this particular mRNA has been silenced.
RNA interference is important in the defense against viruses, particularly in lower organisms. Many viruses have a genetic code that contains double-stranded RNA. When such a virus infects a cell, it injects its RNA molecule, which immediately binds to Dicer. The RISC complex is activated, viral RNA is degraded, and the cell survives the infection. In addition to this defense, higher organisms such as man have developed an efficient immune defense involving antibodies, killer cells, and interferons.
Jumping genes, also known as transposons, are DNA sequences that can move around in the genome. They are present in all organisms and can cause damage if they end up in the wrong place. Many transposons operate by copying their DNA to RNA, which is then reverse-transcribed back to DNA and inserted at another site in the genome. Part of this RNA molecule is often double-stranded and can be targeted by RNA interference. In this way, RNA interference protects the genome against transposons.
RNA interference is used to regulate gene expression in the cells of humans as well as worms. Hundreds of genes in our genome encode small RNA molecules called microRNAs. They contain pieces of the code of other genes. Such a microRNA molecule can form a double-stranded structure and activate the RNA interference machinery to block protein synthesis. The expression of that particular gene is silenced. We now understand that genetic regulation by microRNAs plays an important role in the development of the organism and the control of cellular functions.
RNA interference opens up exciting possibilities for use in gene technology. Double-stranded RNA molecules have been designed to activate the silencing of specific genes in humans, animals or plants. Such silencing RNA molecules are introduced into the cell and activate the RNA interference machinery to break down mRNA with an identical code.
This method has already become an important research tool in biology and biomedicine. In the future, it is hoped that it will be used in many disciplines including clinical medicine and agriculture. Several recent publications show successful gene silencing in human cells and experimental animals. For instance, a gene causing high blood cholesterol levels was recently shown to be silenced by treating animals with silencing RNA. Plans are underway to develop silencing RNA as a treatment for virus infections, cardiovascular diseases, cancer, endocrine disorders and several other conditions.
