The computer we have in every cell

An interview with Prof. Uri Alon on the occasion of his winning the Bruno Prize

Prof. Uri Alon from the Weizmann Institute investigates the seam between physics and biology. In each of the cells in the human body, and in fact in every living cell, there are a kind of "biochemical computers", consisting of thousands of types of proteins. Some of these proteins are used as sensors that perceive what is happening in the environment and transmit information to other proteins through chemical reactions. As a result, the cell performs actions such as division, suicide, change of place or composition and more.

According to Prof. Alon, malfunctions in this computer are the basis of many diseases, when the cells perform actions they are not supposed to perform. In recent decades, much knowledge has been accumulated about the proteins and the reactions that occur between them, but there is still a gap between this information and the understanding of the biological action of the cells, which is the joint action of many proteins and other components acting as a system. "In the laboratory at the Weizmann Institute we try to understand the design principles of biological circuits. The research is based on mathematical models and high-precision experiments, in which we decipher the function of proteins inside living cells", he explains.

"The best-known discovery of the laboratory was in 2002. We came to the conclusion that the network of reactions between the various proteins in the cell, which could have been infinitely complicated and which includes thousands of reactions, actually consists of a small number of patterns that repeat themselves over and over again. Each of these patterns can be compared to a basic circuit of proteins that performs a specific action, such as filtering noises, determining the exact time order of actions or trying to sum or perform an integral and derivative (just as the derivative action makes it possible to detect changes with high sensitivity, so do certain proteins within the cell). We call these patterns motifs, and they are equivalent to recurring motifs in painting or music. These motifs, which turned out to be present in all types of cells, provide scientists with a language in which to talk about the basic circuits of the cellular computer. Since then they have been studied here and in many laboratories around the world. The motifs are considered one of the cornerstones of a new field - SYSTEMS BIOLOGY."

Alon, who wrote the main textbook in this field, explains that in order to investigate these circuits, the laboratory team developed experimental methods to observe the action of proteins inside living cells, with bacteria and human cancer cells taken as primary models. According to him, each such circuit requires a complete research program, as do issues such as building complex systems by combining several such basic circuits.

In Alon's laboratory, the researchers also examined how these mechanisms evolved. They are especially intrigued by the question of why the cell in general consists of such a small number of basic circuits. From the point of view of the researchers, this is indeed a useful feature, which allows them to understand their operation, but why did nature develop this mechanism? "The principle of assembling complicated systems from simple components is well used by engineers," he explains. "It is possible that biological systems have design principles similar to the design principles of engineering, because these principles are the only way complex systems that function in the world can be maintained. The basic research on such principles is a good starting point for understanding how the computers in the cell work, and in the future also to get to the root of diseases caused by disruptions in the cellular computer."

Curiosity led Alon to engage in basic science. "It is very important to emphasize that the most important practical inventions or breakthroughs that have affected our lives resulted from discoveries by scientists who followed their curiosity without the intention of solving a practical problem. Therefore, basic science is important not only as a cultural activity of acquiring new knowledge, but also to find unexpected breakthroughs".

How do we even arrive at such basic science in the 21st century, is an interesting question in itself, because always when we think we understand the operation of a system, it turns out that there is another layer in nature. According to Alon, understanding the cellular system depends on so many pieces of information, that it took decades until scientific activity was able to provide the required knowledge about the proteins and their interactions, which would allow scientists to go through a phase - and develop a mathematical description of a protein system that works together. "In addition, technological developments were also required that allow us to observe the actions of the proteins", he says. "From this knowledge base we can reach a new level of understanding about the integration of the parts into systems, which can be understood at the same level as systems in physics and engineering are understood. These studies make it possible to better understand how the biological circuits that make up the cellular computer are built. Over the years there was such a current in biology, but today it has turned from a marginal current into a major field. Happily, breakthroughs in this field are taking place in Israel, for example the work of Naama Barkai, who received the Bruno Prize several years ago."

Despite his amazing achievements, it turns out that biology is not Alon's only field of interest. "I'm interested in finding bridges between the behavioral sciences and the humanities and the natural sciences," he says. "One direction is to add education and language during the training of the scientists, so that they acquire more knowledge about interpersonal relationships and emotional and subjective aspects of science. This will lead to an environment that will improve the quality of life in science and, in my opinion, will also enable more original science. In particular, education that opens the "political eyes" of doctoral students and young scientists is important, so that we do not become passive. Only united scientists can protect science as a profession from cuts and attempts to bite its public status."

The person who influenced me the most: Dov Schwartz and David Mokamel, who were my PhD supervisors. When I guide students I hear their voices in my head, and I am grateful.

My opinion on the state of education in Israel: The State of Israel has tremendous cultural and scientific potential thanks to the abilities of its residents, therefore it is important that education, research and culture be the state's top priority.