Revealer of the mystery of the transcriptional mechanism of eukaryotic cells

Character biography
Roger David Kornberg (April 24, 1947—), American biochemist, professor of structural biology at Stanford University School of Medicine. The 2006 Nobel Prize in Chemistry was awarded for research on the replication of genetic information from DNA to RNA.

Born in the “Nobel Prize” family
On April 24, 1947, Roger David Kornberg was born in a Jewish family in St. Louis, Missouri, and was a Nobel laureate, biochemist Arthur Kornberg and the same creature. The eldest son of the chemist’s three sons, Sylvie Ruth. Born in such a family, Kornberg received a good science education from an early age. At the age of 12, his father won the Nobel Prize in Physiology or Medicine, but his father was very low-key because he did not want his children to be young. With this aura and pressure, we lose the ability to create independently and think independently.

It wasn’t until after growing up that Kornberg and his brothers knew that the father was such a famous scientist, but at that time they had already become confident adults. Father’s unique educational approach frees Kornberg from the pressure to better pursue his dreams. Years later, Kornberg also achieved great achievements like his father.

In Cohenberg’s memory, his father always patiently tells them all kinds of interesting science stories, but this unintentional will soon become a “green shade” – the father’s casual story is edited into a book: “The Story of Microorganisms”, this simple, lively and interesting science book has also been translated into a variety of words, benefiting many curious children in the world.

In such a tolerant, imaginative family atmosphere, Kornberg has naturally embarked on the path of science. In 1967, he earned a bachelor’s degree in chemistry from Harvard University. In 1972, he received his Ph.D. from Stanford University. He studied under the famous scientist Harden McConnell, and his scientific career began.

Open up new areas
Later, Kornberg came to the Molecular Biology Laboratory at the University of Cambridge, England, where he became a postdoctoral researcher, where he studied an important method of physical and chemical analysis of macromolecules: X-ray diffraction. In the search for X-ray diffraction research questions, a paper entitled “General Models of Higher Biological Chromosomes” caught his attention. An illustration in the paper shows a DNA ring crossed by a dotted line, symbolizing a Histone molecules. This area involves chromatin X-rays, and Kornberg is excited about it, but his colleagues have reminded him that this is a tricky issue. Kornberg wrote in his memoirs: “It may be more appropriate to use the notorious term. Many people succumb to the temptation of this problem because it has the potential to gain insight into genetic chemistry, but the result is that it is difficult to deal with by histones. Frustrated by sex. These proteins, which look very simple, are actually extremely complicated.”

In fact, there are only five types of histones, namely H1, H2A, H2B, H3 and H4. Once isolated, a single histone has a very strong viscosity, can bind tightly to DNA, and can interact in a variety of possible combinations.

But these difficulties did not prevent Kornberg from marching into the area of ​​interest to him. Like every newcomer, he began to repeat the work of others, separating individual histones, mixing them with DNA in various combinations, and recording their X-ray diffraction patterns. In 1978, Kornberg became a faculty member of the Department of Structural Biology at Stanford University School of Medicine, and together with his wife, Yahli Lorch, began research into the effects of nucleosomes on transcription. They found that nucleosomes are the basic protein complexes that encapsulate chromosomal DNA in the nucleus of eukaryotic cells (chromosomal DNA is often referred to as chromatin to reflect this protein packaging). In the nucleosome, Kornberg found that about 200 bases of DNA were wrapped around the octamer of histones. Kornberg and colleagues demonstrated the existence of histone octamers, determined the regulation of nucleosomes in transcription, and opened up a whole new field, which is one of the active fields in today’s biological sciences.

Reveal the mystery of transcription
It is well known that the growth, development, and variation of all eukaryotes are controlled to some extent by genes. A gene is a fragment of a DNA molecule carrying genetic information on a chromosome. Many genes, like codes in different sequences in a computer, have different coding divisions that affect the growth and development of living things. However, these DNA molecular fragments do not directly affect the organism, and most of them must pass through the protein to directly act on the organism.

DNA is relatively stable, and the amount of information stored is huge. Each DNA double strand contains a large number of genes, just like an encyclopedia. When the expression of a certain gene is needed, if the whole copy is performed, the workload will be enormous. Just like a library, all the books are bound together into a huge book. When we need to borrow a book, we have to move this “big book” home. Of course, the process of gene expression is not the case. When an organism wants to use a certain gene, it will “copy” the gene sequence from the entire DNA sequence. This process is transcription. However, just as the “copying” in real life may go wrong, the transcription process of the gene may also be disordered, such as cancer and heart disease. So, if you can find the mechanism behind transcription, then you can help people find a way to treat the disease.

When a cell wants to express a gene, it “copyes” (transcribes) the DNA sequence of the gene to the messenger RNA (mRNA) sequence, possesses the function of “copying” mentioned above, and is responsible for synthesizing the encoded protein. The enzyme of mRNA is called RNA polymerase II. Eukaryotic RNA polymerase is not capable of gene transcription alone. It requires a complex paraprotein assembly to perform this task accurately and efficiently. But how did this process go, no one could give an answer before Kornberg, so he was determined to find out. In 1978, he became a professor of structural biology at Stanford University School of Medicine and led a research team to begin research in this area.

They successfully developed a transcription system from Baker’s yeast (a simple single-cell eukaryote) that was used to purify dozens of proteins required for transcription, in the process, Kornberg It was discovered that the transfer of gene regulatory signals to RNA polymerase is an additional protein complex that they refer to as intermediaries. The complexity of eukaryotes is actually formed by the good interaction between tissue-specific substances, enhancers in DNA, and intermediaries. The discovery of intermediaries is an important milestone in understanding the transcription process.

While working on transcriptional processes, Kornberg is also working on methods to visualize the atomic structure of RNA polymerase and its related protein components. After years of research, he finally created a real picture of how transcription is carried out at the molecular level, and the exact locations of DNA, polymerase and RNA were constructed. The Nobel Prize Committee commented: “The revolutionary part of Kornberg’s painting is that it captures the process of transcription.” In 2006, he won Nobel Chemical because of his great contribution to gene transcription research. prize.

Kornberg’s research has won him numerous awards, such as the Israel Institute of Technology Harvey Award in 1997; the Pasaro Cancer Research Award in 2002; and the Louisa Gross Horowitz Prize from Columbia University in 2006.

Open the window of the future
Kornberg’s family has also made important contributions to biological research. In 1959, his father Arthur Cohenberg won the Nobel Prize in Physiology or Medicine for his research on how genetic information can be transferred from one DNA molecule to another during DNA replication. Specifically, Arthur Cohenberg isolated the first enzyme capable of synthesizing DNA, the bacterial DNA polymerase I, which was the first known enzyme to obtain instructions from the template at the time, thus ensuring cell growth. And preservation of genetic information during the process of division. This family is committed to understanding how genetic information works in cells. It is with the tireless efforts of them and many biochemists that people can see the actual process of eukaryotic transcription.

Today, Kornberg is also conducting the synthesis of large heavy-atom clusters with the aim of performing amorphous structures at near-atom resolution. Cohenberg believes: “This work opens a window to a whole new field of inorganic chemistry and materials science, through which we can enter the future.”