The primary obstacle to creating such complex structures has been the excitons’ short lifespan. They vanish the instant they are formed, making it difficult to amass enough of them in a sufficiently dense pack to flow as a liquid. The idea then, was to extend the survival of excitons. To do this, the researchers used multilayered materials composed of sheets just a few atoms thick. Growing such finely layered materials is one of the specialties of the submicron center at the Weizmann Institute. Within the layers, the scientists created “quantum wells” to trap the electrons, along with their holes.

 

By designing the structure of the material so that the quantum wells were very close together and then applying an electric field, the researchers managed to produce a situation in which the electrons were trapped in one layer while their holes were stuck in the next layer. Though the mutual attraction was still there, and thus an exciton still formed, the separation of the layers made it much harder for the electron to reunite with its hole. The scientists found that they could use the intensity of the electric field to control the life span of the excitons.  

 

Prof. Israel Bar-Joseph’s research is supported by the Carolito Stiftung; and the estate of Toni Fox. Prof. Bar-Joseph is the incumbent of the Jane and Otto Morningstar Professorial Chair of Physics.
 

We can see the external signs of aging – wrinkles and gray hair – but its central processes are hidden from sight within tissues and organs. One of these processes, called cellular senescence, occurs when cells keep functioning but stop reproducing. A better understanding of this senescence may in the future help keep the body's tissues “forever young,” so as to prevent cancer or degeneration of organs or treat aging-related diseases.

 

During the postdoctoral studies he conducted at Cold Spring Harbor Laboratory in New York before coming to Weizmann, Krizhanovsky and his colleagues revealed that cellular senescence plays a much more active role in fighting and preventing various diseases than previously thought. For example, tumors shrink during chemotherapy not only because cancer cells self-destruct, but also because a rising number of these cells becomes senescent.

Moreover, Krizhanovsky discovered that in the liver, cellular senescence is necessary to prevent disease. When liver cells are damaged by the hepatitis virus, fatty liver disease or alcohol abuse, cells called fibroblasts start dividing to repair the damaged tissue. Krizhanovsky found that when the fibroblasts undergo senescence and stop reproducing, the repair process stops and the tissue can return to the normal, pre-damage state. This senescence is needed to prevent a different kind of damage: It averts fibrosis, the overproduction of scar tissue by the fibroblasts, which in turn can lead to cirrhosis of the liver, a common cause of death in developed countries.  

Krizhanovsky then showed that yet another important phase in the healthy maintenance of tissues is the clearance of such senescent cells from the body. In the liver, the immune system’s “natural killers,” the NK cells, enter the picture, removing the senescent fibroblasts. If the removal is impaired or if the fibroblasts don’t become senescent, the result is continuous liver damage. “Cellular senescence provides first aid, like a clamp fastened on a torn artery to stop bleeding,” Krizhanovsky says. “But just as the clamp will cause harm if it’s not removed in time, so senescent cells that are not cleared properly from the body start releasing inflammatory substances, which in the long run cause damage to surrounding tissues.”
 

 

In more recent research conducted at the Weizmann Institute, Krizhanovsky uncovered the molecular mechanisms that underlie the clearance of senescent cells. He identified the receptors on their surface that help their identification by the NK cells; in addition, he found that the NKs kill the senescent cells by releasing a protein that perforates cellular membranes and lets a killer protein get into the cell.

With the help of drugs based on these mechanisms, it may be possible in the future to prevent fibrosis of the liver or other organs, or to treat aging-related diseases, such as certain forms of arthritis or atherosclerosis, in which senescent cells are involved. The drugs will help remove senescent cells that the body is not clearing properly.

Such drugs may also help prevent cancer. In the past few years, scientists have shown that cellular senescence is one of the body’s natural mechanisms for blocking cancer in its early stages. That is probably the reason many precancerous growths, such as moles that with time might turn into melanoma, contain a large proportion of senescent cells. An efficient removal of these cells from the body may help avert the transformation of precancerous lesions into full-blown cancer.

And in a more distant future, it may even be possible to remove senescent cells from tissues to delay aging and promote health over the years.

From Embryos to Aging Cells

During his doctoral research at the Hebrew University of Jerusalem, Dr. Valery Krizhanovsky studied the fate of cells in embryonic development. But his interest in cellular fate in more general terms ultimately led him to the other extreme of the cellular lifespan: senescence.

Krizhanovsky, born in Ukraine, had begun his studies at the University of Kursk in Russia, in the faculty of pharmacology. When he immigrated to Israel with his parents in 1991, he continued his studies at the Hebrew University. Starting in 2005, he went on to conduct postdoctoral research at Cold Spring Harbor Laboratory in New York, before joining the faculty of the Weizmann Institute in 2010.

Krizhanovsky lives in Rehovot with his wife Regina and their two daughters, Maya and Mika. In his spare time, he enjoys reading, particularly on theories and the psychology of economics.
 

 

Dr. Valery Krizhanovsky’s research is supported by the Simms / Mann Family Foundation; the Victor Pastor Fund for Cellular Disease Research; and Lord David Alliance, CBE. Dr. Krizhanovsky is the incumbent of the Carl and Frances Korn Career Development Chair in the Life Sciences.

 

 

 

 

 

Dr. Ron Milo and research students Niv Antonovsky and Lior Zelcbuch of the Plant Sciences Department turned their sights on astaxanthin because the algae that produce it are hard to cultivate, and they require special conditions to make the metabolite. For Milo and his group, this was a side project. They are working with the bacterium E. coli to see if they can coax it to absorb carbon dioxide from the atmosphere, as plants do. The scientists use E. coli – the workhorse of the genetic engineering field – because its genome is well known and easy to manipulate. Convincing the bacteria to produce astaxanthin would be a sort of test case for some cutting-edge methods of genetic engineering the scientists are using in experiments.

 

In other words, a good deal of fine-tuning is needed. To achieve the best levels of efficiency, the researchers applied genetic engineering techniques to a number of genes at once in the E. coli. From this they obtained thousands of different strains, from which they could select those with the desired properties. To adjust the output of the steps in the metabolic pathway they used a sort of “volume control button” on each gene. This is a segment at the beginning of the gene that gives instructions to the ribosome – the cellular factory that translates the genetic information to proteins. Small changes in the sequences of these segments can lead to significant differences in the intensity of gene expression.

 

To begin with, the research team generated random mutations in the “volume control buttons” of the genes involved in astaxanthin production and then inserted these genes into E. coli. The bacteria in their lab dishes began to produce engineered enzymes, and these, in turn, produced the different intermediate metabolites on the astaxanthin metabolic pathway.

 

How did the team identify the strains that produced astaxanthin the most efficiently? Here nature came to the scientists’ aid: Astaxanthin is pink, and thus the bacterial colonies that were the loveliest pink color were those that had the most finely tuned metabolic pathways for its production. The most promising strains then underwent biochemical analysis to quantify astaxanthin levels. The best of these was found to yield over five times as much astaxanthin as other research groups around the world had managed to produce through metabolic engineering in bacteria. These results recently appeared in Nucleic Acids Research.

Milo and his group believe that this method could be used, in the future, in metabolic engineering to improve efficiency in the production of bioactive substances and drugs.
 

Dr. Ron Milo's research is supported by the Mary and Tom Beck-Canadian Center for Alternative Energy Research; the Lerner Family Plant Science Research Endowment Fund; the European Research Council; the Leona M. and Harry B. Helmsley Charitable Trust; Dana and Yossie Hollander, Israel; the Jacob and Charlotte Lehrman Foundation; the Larson Charitable Foundation; the Wolfson Family Charitable Trust; Charles Rothschild, Brazil; Selmo Nissenbaum, Brazil; the Anthony Stalbow Charitable Trust; and the estate of David Arthur Barton.  Dr. Milo is the incumbent of the Anna and Maurice Boukstein Career Development Chair in Perpetuity.