Weizmannviews

I s s u e N o. 2 0 WEIZMANNviews ADVANCING MEDICINE: From Proteins to Personalized Treatments In the future, the practice and precision sion of genes, in the bacteria Escherichia coli of medicine may be very different from (E. coli). The scientists reduced the vast tree what they are today. Prof. Uri Alon of the of chemical reactions to a simple collection Department of Molecular Cell Biology at of four kinds of recurring patterns, known the Weizmann Institute of Science foresees as network motifs. Each network motif a future in which medicine is predictive, carries out a specific function, or computa- personalized, accurate, and rational. In fact, tion, and represents an elementary way that he has already begun to set the groundwork these proteins interact. “The same network for this transformation by identifying com- motifs, the same patterns, were found in mon recurring patterns in the way proteins bacteria, plants, flies, mice, humans, and all organisms,” says Prof. Alon. “There- fore, there is a shared language, not Prof. Uri Alon is working toward only in our genes, but also in the way a future in which medicine is that they are wired together to make predictive, personalized, accurate, cells live or die properly.” and rational. Armed with this improved understanding of protein interactions, Prof. Alon set his sights on medicine. Prof. Uri Alon Specifically, he looked at cancer and interact, and developing a novel method why some human cancer cells respond to for essentially spying on living cells as they chemotherapy by dying, while others sur- undergo chemotherapy. vive it, allowing the cancer to live on. Prof. Alon received his Ph.D. in theo- For several years, Prof. Alon and his re- retical physics, but was also fascinated with search team worked with identical (from biology. These dual interests resulted in his the same parental cell) lung cancer cell being one of the first scientists to explore lines in order to analyze the activities of a field now known as systems biology, in about 1,000 proteins inside the cells. They which biology, computer science, math- looked at the activities of single proteins ematics, chemistry, and physics are inte- inside single cells, instead of creating and grated in order to understand organisms as analyzing a mixture of millions of cells. complete systems. Time-lapse fluorescent microscopy was Cells contain thousands of proteins, similar used to obtain movies of the proteins over to, as Prof. Alon puts it, a very complicated several days, as the cells responded to a story with thousands of characters. Yet he chemotherapy drug. The team also em- and his research team were able to decipher ployed a protein-tagging strategy that the intricacy by focusing on transcription made cells more identifiable by image- factor proteins, which control the expres- analysis software, and ultimately were able WEIZMANNviews Prof. Alon’s research is now focused on creating drug combinations, or cocktails, that to measure the levels and locations of pro- cells from the sick state to the healthy state, can make sick teins in individual cells. effectively acting as a “hospital for cells.” cells healthy. Prof. Alon’s innovative technique gave This new method of cellular espionage him an unprecedented view, leading him signifies progress toward Prof. Alon’s vision to discover that most proteins behaved of future medicine, in which doctors will the same in cells that survived or died. one day have access to the blueprint of an individual patient’s cells. Using this blue- “ There is a shared language, print, doctors could practice preventive not only in our genes, but also medicine, based on a person’s predisposi- in the way that they are tion for a particular illness or condition, and wired together to make cells prescribe individualized drug cocktails that live or die properly.” will be effective in that particular patient. “In this kind of blueprint analogy—which However, two proteins in this experiment is very rational—we know exactly what showed remarkable behavior. Cells that each drug is going to do to a particular started making a lot of these two proteins person. We won’t be guessing, but, rather, survived; cells that did not, died. In addi- understanding why drugs work on one tion to the chemotherapy drug, Prof. Alon’s person and not another,” explains Prof. team also gave the cells a reagent that Alon. This transformation in medicine still stopped the production of these two par- requires more basic research, modifica- ticular proteins, and found that when the tions in the way doctors are trained, and cells could no longer make those proteins, fundamental changes in drug development; they died much faster. “With this method, however, Prof. Alon is not the only scien- you can identify molecular differences from tist who foresees that it will be economi- cell to cell, and also a way to overcome cally beneficial and applicable not only to these differences,” says Prof. Alon. His re- diseases, but also to other aspects of human search is now focused on creating drug physiology, such as aging. combinations, or cocktails, using time and dose combinations, mathematical models, Prof. Uri Alon’s research is supported by the Kahn and experimental methods that can take Foundation and Keren Isra–Pa’amei Tikva. 7.2010 The Weizmann Institute of Science in Rehovot, Israel, is one of the world’s foremost centers of scientific research and graduate study. The American Committee for the Weizmann Institute of Science is a community of dedicated people who share a common vision in support of the Institute. The generous assistance the Institute receives from individuals, foundations, and corporations is vital for its future. Committee members show their devotion to the advancement of the Institute’s goals by becoming partners in the search for answers to the most difficult challenges facing humanity. 633 THIRD AVE • NEW YORK, NY 10017 • 212.895.7900 • WWW.WEIZMANN-USA.ORG.

Load more