And now: the proteome project

The human genome project is nearing completion. But what do the tens of thousands of proteins discovered in each cell? The scientists tighten their belts and start the next big operation

By Yanai Ofran

The idea that was the basis of the human genome project was requested almost automatically: on top of the DNA are the genes - the instructions for the production of all the substances that the cell knows how to produce. According to these instructions, the cell produces different types of proteins. You can take a section of DNA and use relatively simple chemical methods to decipher its instructions. This way it is possible to determine which proteins the cell produces according to the instructions in the section and what is the chemical composition of each of them.

The initiators of the Human Genome Project promoted an international collaboration whose purpose is to decipher the entire DNA sequence found in human cells. This way it will be possible to determine which proteins a human cell can produce and what their chemical composition is.

Philosophers in Grush rushed, with the beginning of the project, to discuss what seemed to them at the time to be the end of biology's path; When the genome is deciphered, they rejoiced, we will already know how everything works. A first draft of the human genome is expected in the coming months, but, as expected, the findings produced by the huge project provide more questions than answers.

Thousands of types of proteins, and sometimes tens of thousands, work like machines inside the cell, in full coordination. The manufacturing instructions for all these machines are found in the NA. The cell operates a system for transporting materials between its various parts, maintains contact with the external environment, absorbs materials from the outside and expels materials, maintains contact with other cells, regulates the concentration of materials within it, draws water from the outside as needed, brings in food but prevents the entry of toxins, produces for itself energy, replicates, activates sensitive control systems that coordinate its life cycle, and even commits suicide on the altar of the good of the body, if necessary. The management of this system requires a complicated system for passing messages between the parts of the cell. All this is done through the proteins that are produced under the instructions of the genes. The hope was that deciphering the complete human genome would clarify the functioning of this complicated system.

The human genome will not be the first genome to be fully deciphered. It was preceded by the genomes of several bacteria, yeast, and also one species of fly. The same problem repeated itself in all of them: a new gene containing instructions for the production of a certain protein was discovered, it is possible to determine what the chemical composition of this protein is, what is its length, what is its weight, and rarely even what it looks like. But what does this protein do? The genome project is not able to answer that. The research that tries to find out the role and importance of new proteins is lengthy and complex, and thus the databases accumulate more and more details about new proteins that no one knows what their role is and what their biological importance is.

A study published at the beginning of this month in the journal "Nature" offers a solution to the problem - a new method that will allow mapping all the proteins that work within one cell.

how does it work The researchers, led by Peter Atz of the Kura-Gan biotechnology company, worked with yeast. The genome of the baker's yeast was already deciphered three years ago. It has 6,000 proteins. The chemical composition of all of them is known, but only a few of them were able to find out what they do in the cell.

The new study used a method called the "hybrid method". The researchers assumed that if two proteins are involved in one process, then at some point in their activity they should bind to each other or at least come very close. If it will be possible to find out which proteins maintain contacts between them, it will be possible to know that they function in the same process. In this way, the researchers will be able to divide the proteins into groups, each of which is involved in the same process. Deciphering the role of one protein in each group will allow tapping into the role of the other proteins in its group.

The researchers developed a strain of yeast in which there is a gene that dyes the yeast a special color (reported gene). They divided the protein mechanism that reads the production instructions of the dye and produces it into two halves. One half was bound to one protein and the other half was bound to another protein. The assumption was that if these two proteins cooperate, then there is a stage where the two parts of the mechanism are re-linked, and the mechanism can produce the color.

The researchers spread tens of thousands of yeast colonies on a special plate. In each colony, the two parts of the apparatus were bound to two different proteins. Only colonies where the proteins cooperated were colored. This is how they managed to discover the role of hundreds of new proteins.

In fact, the new study offers the beginning of the next project that biology will probably face - the attempt to understand the enormous amount of information that the genome project produced. Even there they have already given enough money to this project - if the gene system of an organism is called a genome, then the system of proteins (proteins) of an organism is called a proteome.
{Appeared in Haaretz newspaper, 27/2/2000{

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