Presentation Speech by Professor Lars Thelander, Member of the Royal Swedish Academy of Sciences, December 10, 2006

Professor Lars Thelander delivering the Presentation Speech for the 2006 Nobel Prize in Chemistry at the Stockholm Concert Hall. Copyright © The Nobel Foundation 2006 Photo: Hans Mehlin

Your Majesties, Your Royal Highnesses, Ladies and Gentlemen,

This year’s Nobel Laureate in Chemistry is receiving the award because he succeeded in creating a molecular model of the apparatus in our cells that copies information in the genes to enable its use as a blueprint to create the proteins that perform all the functions in the cells and form the body.

The genetic information that we inherit from our parents is stored inside the nucleus of our cells in the form of DNA. This information is encoded in an alphabet consisting of four letters and for some years now we have known the sequence of the 3 billion characters that describe the genetic information in a human cell. The nucleus of a cell is a very secure repository that could be compared to a safe, but stored inside it the information is passive and of no benefit to the cell. To regulate the processes in the cell the information has to be extracted from the DNA and activated, and this occurs when selected sections are copied into a new type of molecule called RNA. In the form of RNA, the information can then be transferred from the nucleus to regulate the synthesis of proteins and other important reactions in the cell.

Copying the information from DNA to RNA is called transcription. This takes place continually in living cells and is absolutely essential for life. Transcription has to fulfil two different requirements. The first is that the copy must be exact. No more than one error in 10,000 characters can be tolerated, if a cell is to function. Secondly it must be possible to regulate the transcription so that only certain elements of the genetic information in the DNA are activated in a specific cell at a specific time. It is this regulation that explains why different cells in our body look completely different and have different functions, even though they contain the same DNA. Regulation of transcription governs the way in which a fertilised ovum can develop into an embryo and also how our cells can respond to external signals so that we can adapt to changes in our environment. Errors in the regulation of transcription may result in illnesses such as cancer, heart disease and various inflammations.

This year’s Laureate in Chemistry, Roger Kornberg, has studied what the transcription apparatus looks like in eukaryotes, organisms with cells that have a defined nucleus, which include all fungi, plants and mammals, human beings as well. In choosing the model system for his studies he swam against the stream and selected baker’s yeast, which is one of the simplest eukaryotes. This was a crucial choice, as yeast cells offer a number of advantages in this endeavour compared to the cells from mammals that had previously been used. For instance, it is possible to cultivate yeast on a large scale and to benefit from the simplicity with which yeast cells can be modified genetically. The transcription apparatus in yeast cells is very similar to the corresponding system in mammal cells, which suggests that it came into being at a very early stage of development.

By combining biochemical methods and a depiction technique called X-ray crystallography, Roger Kornberg succeeded in producing particularly detailed molecular models of the transcription apparatus in yeast cells. These models are so detailed that individual atoms can be discerned. Through the study of a host of different models of the transcription apparatus both on its own and while fully engaged in copying DNA to RNA, Kornberg has been able to draw new, important conclusions about the mechanisms of transcription and how it is regulated. As a result of his study we now understand, for instance, how the transcription apparatus chooses where to start copying on the DNA strand, how it selects the correct RNA building blocks and how it moves along the DNA strand while the copy is being made.

Kornberg’s molecular models of the transcription apparatus are essential for any continued studies that attempt to acquire detailed understanding of how transcription is regulated. He has recently published very promising results that describe how several molecules that are also needed in transcription bind to and cooperate with the transcription apparatus. These findings make it possible to begin to understand at a molecular level the system of regulation in the cell that expresses the genetic information in DNA and generates the flora and fauna of living creatures that we see around us.

Professor Kornberg,

Your studies of the molecular basis of eukaryotic transcription have provided us with new, detailed atomic models of the transcription apparatus. We can now begin to understand at molecular level the mechanisms of transcription and its regulation. Furthermore, your structure of RNA polymerase II is the basis for the next generation of research to determine the precise role of all transcription factors in transcriptional regulation. On behalf of the Royal Swedish Academy of Sciences, I wish to convey to you our warmest congratulations, and I now ask you to step forward to receive the Nobel Prize in Chemistry from the hands of His Majesty the King.