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Science Feature Articles</p>

Smooth Turbulence

English

Prof. Edriss Titi. Real-world problems

 

Water rushing through pipes, currents in the ocean, weather patterns, airplanes taking off, blood running in veins, chemicals churning in a mixer, even milk being stirred into coffee: all are governed by a single phenomenon – turbulence. Scientists and mathematicians have been studying turbulence since the legendary 18th-century mathematician Leonhard Euler formulated the first mathematical equations for describing liquid flow in non-linear patterns. This formula was refined in the next century by Claude-Louis Navier and George Gabriel Stokes, who noted that viscosity, even when minimal, influences fluid motion and incorporated terms to reflect its effect. The Navier-Stokes equations, as well as a number of equations derived from them, are still used today in scientific fields ranging from chemical and aerospace engineering to climate modeling.
 
Nonetheless, these useful equations still hold some puzzles for mathematicians, and the prestigious Clay Institute in Cambridge, Mass., has included the Navier-Stokes equations in a short list of the seven most challenging mathematical problems for the new millenium. Whoever solves any one of them is promised a $1 million prize. The burning question for the Navier-Stokes equations is whether the solutions to them “break” or “blow up” within a finite time period or whether they remain “smooth” ad infinitum. By “breaking,” mathematicians mean that as the solutions progress in time, some of the quantities might become infinite and the mathematical equation would no longer be a valid model for the physical process. In fact, some mathematicians believe that turbulence is linked to an infinite number of solution breaks, which can occur at any moment. However, proof for Navier-Stokes solutions breaking or remaining smooth has never been established – hence the challenge.
 
Prof. Edriss Titi of the Computer Science and Applied Mathematics Department is fascinated by the ways in which mathematics contributes to solving real-world problems: “Physicists ask: ‘What are the mechanisms that underlie this phenomenon?’ Engineers ask: ‘How can I control this phenomenon?’ But it is mathematicians who study the observations of the other two, develop a proper mathematical framework (and once in a while a completely new theory) and apply rigorous methods, to simplify and answer the others’ questions.”
 
Titi has shown that several equations, variations on Navier-Stokes that apply to specific patterns of turbulent flow, are able to produce smooth solutions at all times, with no breaks. The first, which he proved while at Cornell University, was for helical flows. As the name implies, in helical flows symmetrical lines of flow swirl around a central vortex. But this kind of flow, says Titi, is not truly three-dimensional. One can treat the flow lines as though they lie on two-dimensional surfaces, and this reduces the complexity of the problem. Titi and his colleagues proved that helical flows are invariant – once they start they’ll go on forever without breaking, according to the formula.
 
The second set of equations is truly three-dimensional, making it more complex, and Titi’s proof for smoothness at all times in these equations settles a major open problem in the mathematical theory of geophysical fluid dynamics and adds significantly to the under-standing of the field.
 
The equations were originally formulated in the 1920s, for weather prediction, by Lewis Fry Richardson – one of the first to try modeling the complex movement of air around the globe. In doing so, he had to deal with movement along an enormously wide, thin curving layer of fluid. (If the earth were a very large apple, the atmosphere would be the thin peel.) Taking advantage of the shallow atmosphere, Richardson distorted the Navier-Stokes equations, replacing the equation for vertical motion with the so-called “hydrostatic balance” equation, which is based on a simplified balance between the rate of change in pressure with respect to depth and the buoyancy forces. 
 
“Richardson’s ‘Primitive Equations of Large-Scale Ocean and Atmosphere Dynamics’ ruined the elegant symmetry of Navier-Stokes,” says Titi. Mathematically, these equations appear to be more difficult to approach than the original Navier-Stokes, and it was only last year that mathematicians succeeded in proving they possess smooth solutions for even a short period. So it was quite a surprise when Titi and his student were able to prove that these equations are eternally smooth.
 
Titi: “The charm of challenging mathematical problems such as Navier-Stokes is that they can be simply formulated and explained, yet they keep us busy trying to solve them for decades, centuries – sometimes millennia.” 
 

From Akko to Rehovot

 
Prof. Edriss S. Titi was born and raised in an Arab family in the Old City of Akko. His parents barely finished grade school, but they insisted on providing their four children with the best education available, at Akko’s private Franciscan Terra Sancta school. There, with the help of teachers he’s in touch with to this day, Titi excelled in mathematics and physics. In 1974, he began studies at the Technion, in Haifa. 
 
After receiving an M.Sc. in theoretical mathematics from the Technion, Titi switched to applied mathematics, completing his Ph.D. at Indiana University and postdoctoral research at the University of Chicago. He was a lecturer for two years at Cornell University, then moved to the University of California at Irvine, where he became a full professor in 1989. Titi first came to the Weizmann Institute as a visiting scientist in 1999; he joined the Mathematics and Computer Science Faculty in 2003.
Prof. Edriss Titi. Unbroken solutions
Math & Computer Science
English
  • Computer Science and Applied Mathematics
  • Edriss S. Titi
  • Turbulence

Dr. Weizmann’s Bug Strikes Again

English
Prof. Ed Bayer and team. Helpful bacterium
 

 

 
 
Chaim Weizmann would surely be amazed to learn that the bacterium linked to his struggle for the creation of the State of Israel now promises to perform a new international feat.
 
It was while working as a research chemist in Manchester shortly before World War I that Weizmann found a bacterium that produced acetone and butyl alcohol. Though a senior university professor advised him “to pour the stuff down the sink,” Weizmann continued to study the bacterium. History would prove him right. When the war broke out, acetone – needed for producing gunpowder and usually made by distilling wood – was in short supply, and the British government asked Weizmann to develop large-scale production of acetone from maize with the help of his bacterium. He managed to set up the manufacture of considerable quantities of the vital chemical, an achievement that greatly raised his prestige and helped him fight for the proclamation of the historic 1917 Balfour Declaration, which promised the Jewish people a “national home” in Palestine.
 
 
Cellulosome structure
 
 
 
 
 
 
 
 
Current Weizmann Institute research might allow Dr. Weizmann’s bacterium, called Clostridium acetobutylicum, to reveal its prowess in a new field: It may be employed to decrease pollution while producing useful chemicals. In this guise, the bacterium may be harnessed for breaking down cellulose, the main component of plant cell walls and the most abundant type of biomass on Earth.
 
Cellulose is a stable chain of linked sugar molecules that gives wood its remarkable strength and serves as the basic building block for many textiles and paper. To get an idea of its sturdiness, consider the following: A chain of more than seven sugar units is insoluble, and cellulose can contain up to 10,000! In nature, cellulose fibers from trees and plants are degraded by microorganisms in soil and water that possess a molecular machine called a cellulosome – a large protein complex consisting of several enzymes. The cellulosome splinters the tough, insoluble cellulose into soluble sugars, which can then re-enter the plant growth cycle. However, natural cellulosomes are not good at breaking down cellulose in such man-made products as paper. As a result, billions of tons of discarded paper fail to decay in landfills across the planet, creating an environmental problem of enormous proportions.
 
Prof. Edward Bayer of the Weizmann Institute’s Biological Chemistry Department and Prof. Raphael Lamed of Tel Aviv University discovered the cellulosome in 1983 and in subsequent years elucidated its architecture. Now they are building “designer” cellulosomes that, among numerous other applications, would be able to degrade paper waste effectively – either on their own or inside a microorganism. Using genetic engineering and combining different structural elements in a Lego-like design, Bayer and Lamed seek to optimize cellulosome performance.
 
After trying out hundreds of different artificial cellulosomes, the collaborative team selected one consisting of three cellulose-degrading enzymes. The enzymes of this artificial cellulosome have two complementary modes of action: one chops up cellulose by catching it in a cleft, Pacman-style; the other continuously clips the cellulose chain while passing it through a tunnel-like opening. The synthetic cellusome is still far from being ready for use in waste management, but in a laboratory dish it takes only about a day to churn up finely chopped paper into a syrup of two-unit soluble sugars. “Nature can’t deal with paper,” says Bayer, “but we may be able to coax the cellulosome into handling tasks that were not foreseen by evolution.”
 
While Bayer makes use of purified designer cellulosomes, it may also be possible to employ his findings to improve the function of cellulosomes inside whole micro-organisms, and that’s precisely the goal of several research teams around the world. This latter option brings us back to Dr. Weizmann’s bacterium: Its recently deciphered genome was found to contain the genes for a cellulosome. However, like a long-forgotten piece of machinery discovered in the basement during a spring cleaning, this cellulosome is defective and it’s currently not being used by the bacterium. Relying on Bayer’s research, his colleagues in Toulouse and Marseille have recently given this cellulosome a genetic overhaul, trying to convince the historic bug to generate acetone and butyl alcohol from paper waste rather than from maize, as in Dr. Weizmann’s work. Thus the bacterium that once helped create the State of Israel might one day make an industrial comeback thanks to Israeli research.
 
 
Left to right: Prof. Ed Bayer, Jonathan Caspi, Rachel Haimovitz, Ilit Noach, Alon Karpol, Hadar Gilary, Dr. Ely Morag and Dr. Yoav Barak. Designer cellular machinery
Life Sciences
English
  • Bacteria
  • Biological Chemistry
  • Ed Bayer
  • Genetic engineering

To Catch a Thief

English
Dr. Deborah Fass. Stopping a retrovirus
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Retroviruses are the ultimate sneak thieves of the microscopic world. The outer envelopes of these viruses, some of which cause AIDS or cancers such as leukemia, are spiked with protein assemblies that are specialized tools for breaking and entering. There’s no need to force windows or pick locks: The retrovirus' surface proteins simply cause the membrane of the virus to fuse with the cell's outer membrane. Once the two are fused, the genetic material at the heart of the retrovirus, RNA, makes itself at home in the cell, stealing the cell’s most basic equipment to make copies of itself.
 
Viral surface proteins, in turn, make attractive targets for drugs and vaccines – blocking them might stop infection before it can take place. Like detectives on the path of a criminal, scientists need information – mug shots, fingerprints, eyewitness reports – to help them capture their target. A team of scientists at the Weizmann Institute of Science and the Max Planck Institute for Biochemistry has now obtained a close-up, 3-D portrait of a large protein complex responsible for retroviral breaking and entering. Results of their work appeared in the Proceedings of the National Academy of Sciences, USA.
 
The retrovirus protein complex studied by the group recognizes and binds to specific sites on the cellular membrane and mediates the fusion process at the very onset of infection. However, the shape of this complex and the way it works had long evaded efforts at detection by various scientific groups. The difficulty was that crystallization, the leading method of preparing proteins for structure solving, does not work well with the elaborate, envelope-bound complexes, which tend to fall apart when removed from the virus membrane. Dr. Deborah Fass of the Weizmann Institute’s Structural Biology Department had managed to determine the structures of assorted parts of the complex in the past, but she needed a better understanding of how the complex works as a whole
.
To accomplish her goal, Fass and student Nathan Zauberman teamed up with scientists from Max Planck’s Molecular Structural Biology Department in Martinsried, Germany, to try an alternative method of getting an image of the complex. They turned to the electron microscope, a standard tool for observing larger structures such as cell sections. Viewing a single, relatively small protein complex pushed the limits of this technology, but the Max Planck group, expert at developing both the hardware and the software required for visualizing biological structures with electron microscopy, proved up to the task. The technique they used, known as cryo-electron tomography, involves quick-freezing the viruses in liquid ethane, capturing snapshots of them at various angles and then combining the snapshots to create three-dimensional pictures. From dozens of these digitized 3-D pictures of whole viruses, hundreds of protruding surface protein complexes could be cut out, aligned and averaged. Though the resulting image did not have quite as high a resolution as images obtained through crystallography, it allowed the scientists to get a complete and fairly detailed picture of this important protein complex all in one piece and in its natural setting. “After years of trying to imagine how the pieces fit together, suddenly we had the actual structure right in front of us. Some aspects of it looked familiar, but others were completely unanticipated,” says Fass.
 
The scientists were surprised to note that the shape of the complexes on retroviruses bore little resemblance to other known viral envelope protein structures such as those on flu viruses. They also saw strong evidence that the protein complex undergoes a radical change in the shape and arrangement of its component parts as it attaches to cells and initiates membrane fusion. Fass was able to see how a smaller protein piece she had previously isolated and analyzed by crystallization fit into the whole, giving her further clues as to how the virus locks onto the cell membrane.
 
The retrovirus used by Fass and the team is similar to that which causes leukemia in humans. They hope, with further research, to come to understand the conformational changes the envelope protein complex undergoes as it works, and to find ways to stop those changes from taking place, thus disabling a sneak thief’s main tool for breaking into cells.
 
Dr. Debora Fass’s research is supported by the Clore Center for Biological Physics; the Helen and Milton A. Kimmelman Center for Biomolecular Structure and Assembly; and the Leukemia Research Foundation. Dr. Fass is the incumbent of the Lilian and George Lyttle Career Development Chair.
Image of retovirus that causes leukemia

 

Reverse reproduction

The genetic material of retro-viruses such as HIV and the virus that causes leukemia is found in single strands of RNA, rather than in the double-stranded DNA that all living things employ to store genetic information. Unlike living cells, viruses cannot reproduce on their own, and thus they must “hijack” the machinery of a living cell to do so. For this purpose, the retrovirus carries with it a special enzyme, called reverse transcriptase. In normal transcription, RNA is formed from a DNA template, but reverse transcriptase turns this process around, lining up a DNA sequence to match the “letters” in the viral RNA. The “viral” DNA inserts itself into the host chromosome, where it remains to manufacture more retroviruses.
 
 
Dr. Deborah Fass. Protein portrait
Chemistry
English
  • Deborah Fass
  • Retrovirus
  • Structural Biology

Eureka!

English

Prof. Gregory Falkovich. Moving up the wave

 

Archimedes reportedly shouted: “Eureka!” from his bath when he realized that a sinking object displaces a mass of water equal to its weight (as opposed to an equal volume of water). Ever since, the concept of specific gravity, known to schoolchildren and physicists alike, has been a cornerstone of our understanding of the physical world. But a new aspect of this basic law of physics, one that Archimedes never saw, has now been revealed.
 
Prof. Gregory Falkovich, Head of the Physics of Complex Systems Department, has been with the Weizmann Institute since moving to Israel from the former Soviet Union 14 years ago. He found that different types of very small objects floating on an inclined water surface move either upward or downward, depending on whether or not they “love” the water. The explanation: A water-loving, or hydrophilic, material displaces more water, by weight, than its own mass, and the resulting imbalance causes it to be carried upward. In contrast, hydrophobic - water-hating - materials displace less water than their weight, and these materials gradually move down the slope.
 
This surprising new spin on one of the most basic laws of physics was discovered when Prof. Falkovich and Dr. Sergei Lukaschuk of the University of Hull, England, were observing the movements of small beads floating on a standing wave. A standing wave does not really stand, but the water’s movements - up, down, forward and backward - cancel each other out, so that the average movement is zero. In this situation, anything floating on the wave should stay in one place. But the two scientists noted that tiny Teflon beads, which are “water-haters,” moved down the wave, while small, water-loving glass beads advanced up the wave. These findings may help explain, among other things, how oil droplets or pieces of trash form clumps in the ocean.
 
Falkovich: “Revealing a new facet of a basic law of physics is an event that doesn’t happen every day. In a sense, I feel as though I’ve had the privilege of crossing the time barrier and talking to Archimedes, one of the founding fathers of physics.”
 
Prof. Gregory Falkovich’s research is supported by the Gabriel Alhadeff Research Fund and the Edward D. and Anna Mitchell Family Foundation.
Prof. Gregory Falkovich. New spin on a basic law
Space & Physics
English
  • Gregory Falkovich
  • Physics of Complex Systems

Disarming the Alarm

English
 
Cohen and Shai. Evading immune response
 

 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
One of the mysteries surrounding HIV infection is how the virus manages to hide out in the very immune system cells that are meant to protect the body from harmful invaders. How does the virus prevent these cells from mounting a full-scale attack? In the 22 years since the virus that causes AIDS was identified, much progress has been made in documenting how it breaks into the host cell and reproduces once inside the cell; but many questions remain to be answered. A team of Weizmann Institute scientists has added another piece to the puzzle by showing how a part of a protein on the virus’ outer surface interferes with the cells’ normal immune response. But their work may have wider implications: This molecular fragment, which has such a devastating effect in the case of AIDS, might turn out to be an effective treatment for some chronic disorders such as rheumatoid arthritis. The results of this study were recently published in the Journal of Clinical Investigation.
 
HIV infection begins when the protein coatings of viruses fuse with the outer membranes of T cells - members of the primary response team of the immune system. T cells recognize the presence of foreign invaders and alert other types of immune cells to come to the rescue. The genetic material of the virus, which is basically a strand of RNA, forces the cell’s DNA to make copies of it, and the newly minted viruses created by the host DNA later break out of the cell membrane and infect other cells. Many scientists believed that the very act of breaking into T cells and hijacking their DNA was enough to destroy the ability of these cells to call up immune system reinforcements. But Institute scientists Prof. Yechiel Shai of the Biological Chemistry Department, Prof. Irun Cohen of the Immunology Department and graduate students Francisco Quintana and Doron Gerber thought there must be more to the story. T cells identify invaders using receptors, like security antennae, on their outer walls. Viruses, as well, have their own surface equipment for seeking out specific T cells. To the scientists it seemed unlikely that such a virus would be invisible to the T cell - able to slip past its ever-watchful receptors without raising the alarm. They surmised that the virus must actively disable some part of the immune cell’s system.
 
They investigated a protein fragment called FP (fusion peptide), which is an active segment of an HIV protein called gp41 found on the outer envelope of the virus. FP was known to play a role in the complex process by which the viral envelope fuses with the cell membrane in the initial stage of cell infection. The researchers suspected that FP, though it is exposed for only a short period during this process, might have enough time, as well as the capability, to deactivate some of the cell’s intruderalert apparatus on its way in. Indeed, they found that FP locks on to several proteins on the cell walls that are involved in invoking a large-scale immune response, effectively shutting them down.
 
Armed with their new understanding of how a tiny virus can gain control of the body’s immune response, the scientists made an intuitive leap. Could FP, on its own, be an effective tool for controlling harmful immune system activity?
 
Receptor and protein
 
 
 
 
 
 
 
 
 
 
 
 
 
 
In autoimmune diseases, the same T cells that play host to HIV are overactive, mistakenly attacking the body’s cells instead of foreign invaders. The researchers theorized that, since FP selectively blocks one type of immune response, maybe it could be used in a beneficial manner to override the cells’ misguided call for help in cases of autoimmune disease. To check this theory, the research team tested FP on rats suffering from an autoimmune syndrome similar to human rheumatoid arthritis. As they predicted, the rats treated with FP showed a significant reduction in joint swelling and other symptoms of arthritis.
 
Shai points out that using FP, a tiny piece of HIV, would pose no danger to patients as it lacks the ability to either infect cells or reproduce. Indeed, as the scientists note in their paper, the study of a destructive virus may contain important lessons for medical science on how to regulate the immune system. “Perhaps,” says Cohen, “we can adopt the virus peptide to help control overactive autoimmunity.”
 
Prof. Yechiel Shai’s research is supported by the Robert Koch Minerva Center for Research in Autoimmune Disease and the Estate of Julius and Hanna Rosen. Prof. Shai is the incumbent of the Harold S. and Harriet B. Brady Professorial Chair in Cancer Research.
 
Prof. Irun Cohen’s research is supported by Minna James Heineman Stiftung; the Robert Koch Minerva Center for Research in Autoimmune Disease; and Mr. and Mrs. Samuel Theodore Cohen. Prof. Cohen is the incumbent of the Helen and Morris Mauerberger Professorial Chair in Immunology.
 
Illusteration: HIV at the cell membrane
Life Sciences
English
  • Autoimmune
  • Biological Chemistry
  • HIV
  • Immune system
  • Immunology
  • Irun Cohen
  • Viral infection
  • Yechiel Shai

Making a Switch

English

Prof. David Cahen and Adi Salomon. Negative resistance

 

From simple light fixtures to the latest in cell phone technology or medical equipment, electrical switches are wired into the circuit. Whether made of metal contacts or engraved in silicon, their basic function is to stop and start the flow of electrons. But as scientists and inventors attempt to shrink new devices into the realm of nano-technology, the limitations of switches made of these materials are becoming apparent. What will replace them?
 
Prof. David Cahen of the Materials and Interfaces Department and his Ph.D. student and Clore Fellow Adi Salomon think that organic (that is, carbon-based) molecules may hold the answer. They have demonstrated a new kind of electrical switch created from organic molecules that could be used in future nanoscale electronic components.
 
Their approach involved rethinking a phenomenon that drives many of today’s high-speed semiconductors. Negative differential resistance (NDR) – for which its discoverer, Leo Esaki, won the 1973 Nobel Prize – works contrary to the standard laws of electricity. Normally, an increase in voltage translates into an increase in current. In NDR, as the voltage steadily increases, the current peaks and then drops off, essentially constituting a switch with no moving parts. Until now, how-ever, attempts to recreate NDR at the molecular scale were achieved only sporadically, mostly at extremely low temperatures or as an unstable, hard-to-reproduce phenomenon. “In hindsight, most efforts were probably aimed too squarely at trying to force molecules to behave like conventional materials, and too little at exploring the chemistry of the molecules,” say the researchers.
 
Some clues to practical nanoscale NDR emerged from earlier work at the Weizmann Institute conducted by Dr. Yoram Selzer (now at Tel Aviv University) and Salomon, under Cahen’s guidance, on connecting organic molecules to metal wires. They found that molecules and metals, like people, need chemistry between them for the juice to really flow. For a given voltage, if the molecules are held to the wire by chemical bonds (in which the two are linked by shared electrons), the current flowing through them will be many times higher than if they are only touching - a mere physical bond.
 
Using this insight, the team de-signed organic molecules that pass electricity through chemical bonds at a lower voltage, but through physical bonds at a higher voltage. As the voltage approaches the higher level, sulfur atoms at one end of the molecule loosen their chemical bonds to the wire and, as the switchover occurs, the current drops off.
 
But the scientists still didn’t have a functional switch. Once the chemical bond to the wire was broken, the molecules tended to move apart, preventing them from switching back to the chemically bonded state. Prof. Abraham Shanzer of the Organic Chemistry Department, who worked with the team on the original molecular design, helped them create long add-on tails to hold the molecules in place. With this modification, the NDR then became stable, rever-sible and reproducible at room temperature.
 
Cahen and Salomon believe their work supports the notion that the future of miniaturized electronics may lie in methods that combine chemistry with nanoengineering. “We don’t take human-sized objects and try to scale them down; rather, from a different universe of possibilities, we create new things specifically designed to function in the nanoworld.”
 
Prof. David Cahen’s research is supported by Minerva Stiftung Gesellschaft fuer die Forschung m.b.H; the Wolfson Advanced Research Center; the Philip M. Klutznick Fund for Research; and the Delores and the Eugene M. Zemsky Weizmann-Johns Hopkins Research Program. Prof. Cahen is the incumbent of the Rowland Schaefer Professorial Chair in Energy Research.
Prof. David Cahen and Ph.D. student Adi Salomon. Switching bonds
Chemistry
English
  • Abraham Shanzer
  • David Cahen
  • Materials and Interfaces
  • Nanoelectronics
  • Organic Chemistry

Like Human, Like Octopus

English
Prof. Tamar Flash. Octopus arm movement
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The freedom to choose between many possibilities doesn’t always make life easier. For example, deciding which fruit to buy is simple if you’ve stopped by a roadside strawberry stand, but it can be confusing and time-consuming when shopping in an upscale supermarket that sells twenty varieties of apples, alone. Having too wide a choice between possible modes of action turns out to be taxing, demanding of large amounts of the brain’s resources.
 
The octopus has a similar problem in deciding how to move its eight tentacles. Each is completely flexible, allowing movement in any direction from any point along its length. In addition, the tentacle can be extended or retracted, further complicating the choice of movements. In contrast, the human arm moves from a limited number of joints, and movement at each is restricted to a fixed number of planes, or “degrees of freedom.”
 
A joint study by scientists at the Weizmann Institute of Science and the Hebrew University of Jerusalem has revealed how the octopus copes with the generous freedom of choice in limb movement nature has granted it.
 
Movements must be planned and coordinated if they’re to be efficient. In humans, the brain calculates and selects the best joint angles and combinations of muscle contractions for each movement. With its relatively small brain and nearly limitless possibilities for movement, how does the octopus manage? Prof. Tamar Flash of the Weizmann Institute’s Computer Science and Applied Mathematics Department and Dr. Benny Hochner of the Hebrew University’s Neurobiology Department and Interdisciplinary Center for Neural Computation have been on a quest for the last 11 years to understand how the octopus nervous system oversees the control of its unique physiology.
 
They have found that octopi, from all the possibilities open to them, stick to a more or less narrow repertoire of tentacle movement patterns. Each of these patterns, which in combination allow the octopus a wide range of movement, is circumscribed in its degrees of freedom. For example, to reach for an object, the tentacle bends in a kink that advances whip-like down its length - a movement based on only three degrees of freedom. This restriction reduces the number of variables the octopus brain must deal with to calculate the most efficient movement. The results of an earlier study by this research team, which appeared in the journal Science, showed the octopus brain does not bear the full brunt of planning and control in this complicated undertaking. Rather, the brain passes at least part of the task over to smaller “local brains,” fitted on each tentacle, that specifically deal with movement.
 
The most recent study, carried out in the framework of Dr. German Sumbre’s doctoral research in Hochner’s lab and published in Nature, adds another piece to the puzzle. To their surprise, the scientists noted that a specific movement, again carried out within limited degrees of freedom, is repeated each time an octopus brings a piece of food to its mouth. What’s more, this movement looks intriguingly like the movement of a human arm performing the same task.
 
Flexible food grab
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Sophisticated computer analysis helped reveal that the tentacle, as it manipulates the captured food toward the mouth, becomes divided into three rigid segments and bends at the joints between them. The first segment, farthest from the body, functions much like a hand, while the other two appear to act as forearm and upper arm. These last two are always of equal length. The scientists think the tentacle’s “local brain” calculates the midpoint and divides the limb into segments. It then passes responsibility over to the central brain, which synchronizes the movements of the segments. It would appear, they say, that evolution has arrived at similar models of efficient, economic movement for both humans and octopi, the one through a rigid skeleton and the other through limiting the choice of movement patterns.
 
The researchers aim to apply what they have learned about tentacle movement to the world of robotics. Soft, flexible, yet easily controllable robotic arms might be advantageous in many situations for which robots are now being developed. Octopus-like limbs, for example, might allow a robot working in a disaster area to cover un-certain terrain; these robots would also be able to extend their appen-dages around corners, or reach into spaces where other types of tools or machine can’t fit. Such robots would be handy in a number of tasks, including helping out in rescue missions, neutralizing explosives, repairing ships underwater and even performing surgery - thin, flexible tentacles might one day be designed to navigate twisting intes-tines or blood vessels, or to probe small spaces and delicate tissues.
 
Prof. Tamar Flash’s research is supported by the Manfred D. Moross Laboratory for Vision Research and Robotics. Prof. Flash is the incumbent of the Dr. Hymie Moross Professorial Chair.
 
Prof. Tamar Flash. Calculated move
Math & Computer Science
English
  • Computer Science and Applied Mathematics
  • Robot
  • Tamar Flash

The Fat Factor

English

Prof. Michael Walker. Blood sugar and fat

 

Diabetes has become epidemic in the Western world: One out of 12 suffers from type 2 (adult onset) diabetes, and the number of diabetics (presently 150 million worldwide) is expected to double in the next 20 years. Though studies have laid the blame on the growing obesity scourge, the reasons for the strong correlation between excess body fat and diabetes have been puzzling scientists. New research at the Weizmann Institute and in Sweden has revealed exactly how one protein’s response to fat in the bloodstream contributes to the disease.
 
Type 2 diabetes is a complex disorder characterized by the body’s inability to utilize sugar efficiently. Two stages of the disease have been identified: In the first, “silent” stage, the body’s cells lose their ability to respond properly to the crucial hormone, insulin, responsible for moving sugar from the blood into cells. If sugar remains in the bloodstream, the insulin-producing beta cells in the pancreas compensate by stepping up production. Eventually this leads to beta cell exhaustion, reduced insulin output and the appearance of full-blown diabetes.
 
Elevated fat in the bloodstream appears to accelerate both stages of the disease. Exactly how does this happen? Beta cells are attuned to changes in blood sugar levels, responding to after-meal surges with a sharp increase in insulin production. But a recently discovered protein, a receptor on the surface of the beta cell called GPR40, responds not to sugar, but to fatty acids. When fat is present in addition to sugar, the GPR40 receptor causes an even higher spike in insulin output. If beta cells are frequently overstimulated and overworked, persistently elevated insulin levels may hasten the onset of the disease.
 
To investigate GPR40’s role, Prof. Michael Walker and students Nir Rubins and Reut Bartoov-Shifman of the Weizmann Institute’s Biological Chemistry Department teamed up with Prof. Helena Edlund and postdoctoral fellow Dr. Per Steneberg of the University of Umea in Sweden. Together, they developed two types of lab mice with modified GPR40 activity. In the first, the scientists used a technique known as gene knockout to prevent production of the GPR40 receptor. In the second type, overactive GPR40 genes created a surfeit of fat-signaling receptors that tricked the beta cells into sensing high fatty acid levels, even on a normal diet.
 
Throughout the trial, the GPR40 knockout mice remained healthy, apparently suffering no adverse effects from the deletion of the receptor, even when the fat content of their diet was raised substantially. In contrast, normal mice on a high-fat diet displayed typical symptoms of the first stage of diabetes. But strikingly, in the animals with extra GPR40 receptors, the disease progression was swift: They soon began to exhibit the classic symptoms of full-blown diabetes, including failure of the beta cells to produce adequate amounts of insulin.
 
Walker: “Our results establish GPR40 as an important link between obesity and diabetes. This gives us a new tool to combat the diabetes epidemic: It might be possible in the future to treat the condition using drugs that block the action of this receptor.”
 
Prof. Michael Walker’s research is supported by the Laufer Charitable Trust; Ellen Rosenthal; and Mitchell and Cynthia Caplan. Prof. Walker is the incumbent of the Marvin Myer and Jenny Cyker Professorial Chair for Diabetes Research.
Prof. Michael Walker. Linking fat to disease
Life Sciences
English
  • Biological Chemistry
  • Diabetes
  • Michael Walker
  • Obesity

Slow Release

English

Hundreds of potential drugs never make it to the clinic because they don’t stay in the body long enough to do their job. Small proteins shown to be effective against disease are often cleared by the kidneys within minutes and therefore cannot serve as drugs. Now Weizmann Institute scientists have developed a new strategy that could turn numerous small proteins and protein fragments into potent drugs.

 

Shechter, Tsubery and Fridkin. PEGs keep drugs in the body

The plan consists of dramatically increasing the protein’s mass. Like a sprinter weighed down by a heavy load, the modified protein finds its movement restricted; it is not whisked away by the kidneys and can stay in the bloodstream for hours. This approach is based on a method known as PEGylation: several chains of polyethylene glycol, or PEGs, are attached to the protein. PEGylation has been around for nearly two decades, but it hasn’t been widely used to turn small proteins into drugs because it comes with a catch: the same chains that make the protein heavy may also render it nearly useless; they take up its active sites, hindering its healing action in the body.

 

The new Weizmann Institute strategy, which can be described as “reversible PEGylation,” overcomes this problem. The protein is PEGylated with chainlike structures held in place by reversible chemical bonds that dissolve in the bloodstream. Once the chains fall off, the protein’s medicinal action is restored. Moreover, the chains do not all dissolve at once, so the active protein is released in a slow, continuous and predictable manner – an ideal way to provide a steady supply of the drug for optimal effect. The approach was developed by Prof. Yoram Shechter of the Biological Chemistry Department, Prof. Mati Fridkin of the Organic Chemistry Department and Dr. Haim Tsubery of both departments.
 

Potential protein drugs treated with the new approach have already been shown to be effective in laboratory animals. A single injection of a protein fragment drug that reduces blood glucose levels in rodents with Type 2 diabetes was effective for three days. A single injection of a reversibly PEGylated growth hormone, a small protein, corrected the effects of growth-hormone deficiency in rats over a period of four days. And the activity span of a short-lived protein fragment that may be extremely useful in the treatment of obesity and related disorders was extended dramatically following PEGylation by the new method.
 

Several companies with protein drugs in the pipeline have already expressed interest in the new strategy. Yeda Research and Development Co. Ltd., the Institute’s technology transfer arm, has filed a patent application for the approach.   

 

Prof. Mati Fridkin’s research is supported by the Helen and Martin Kimmel Center for Molecular Design; the Paul Godfrey Foundation; the Philip M. Klutznick Fund for Research; the Levine Institute of Applied Science; the Dr. Ernst Nathan Fund for Biomedical Research; and Mr. and Mrs. Luis Stillmann, Mexico. Prof. Fridkin is the incumbent of the Lester B. Pearson Professorial Chair of Protein Research.

 

Prof. Yoram Shechter’s research is supported by the Levine Institute of Applied Science and the Howard M. Siegler Foundation. Prof. Shechter is the incumbent of the Charles H. Hollenberg Professorial Chair of Diabetes and Metabolic Research.

 
Chemistry
English
  • Biological Chemistry
  • Drug
  • Mati Fridkin
  • Organic Chemistry
  • Yeda
  • Yoram Shechter

A-mazing Algorithm

English

Dr. Omer Reingold. Into the maze

People have been trying to find their way through mazes since ancient times. Consider the subjects of ancient Athens, forced each year to send seven youths and seven maidens to Minos, the king of Crete, as tribute. These 14 captives were then sent into an exitless maze that housed the youth-and-maiden-eating Minotaur at its center.
 

Theseus, son of Aegeus, king of Athens, with the help of the besotted Ariadne, daughter of Minos, put an end to the Minotaur and the maze’s notoriety. Just as he was about to enter, Ariadne slipped him a ball of thread. One end of the thread was tied to the maze entrance, and Theseus unwound the ball as he roamed the maze in search of the beast at its center. Of course, he managed to kill the Minotaur and, thanks to Ariadne’s thread, found his way out of the maze in safety.
 

The first lesson to be learned from this story is: don’t venture into a maze unprepared. If you’ve forgotten to bring a spool of thread from home, be ready to go to some trouble to get out. From ancient times, the best method for finding one’s way through a maze required leaving threads or signposts. Even for a computer, the only other approach that did not require a very large amount of memory was randomness. If every time you came to an intersecting path, you randomly decided (by flipping a coin, for example) which direction to take, you would eventually get to the point in the maze you were aiming for. Enter Dr. Omer Reingold of the Computer Science and Applied Mathematics Department. Reingold recently came up with a method that’s deterministic (not based on randomness) yet economical when it comes to memory use.

 

Maze for a modern-day Theseus

 

Why should a computer scientist care about mazes? Because a maze can be used as a model for a network – of computers, airline flight routes, roads, etc. In fact, the ability to find a path through a maze or network is a fundamental problem lying at the very heart of much of computer science. Many complex calculations contain deeply hidden mazes. Questions asked by computer scientists in this field are: How much time and how much memory are needed to calculate the steps needed to get from point A to point B in a maze or on a road map? The time question was solved decades ago, the memory question only partially. It’s known that the algorithm (a computer’s plan of action) for finding the way based on random turnings consumes a very small amount of memory. All that’s required is to remember the present position of the “captive” in the maze. In comparison, deterministic algorithms have been memory-hungry when it comes to solving mazelike problems.

 

Recently, Reingold managed to find a solution to this basic quandary, which has engaged many a computer scientist for the last 35 years. Reingold’s algorithm is both deterministic and able to keep memory use down to levels nearly as low as those of the randomness-based algorithms. Armed with the new algorithm, the modern Theseus can enter his maze equipped with an explicit set of navigating instructions -- for example: Turn right at the second intersection, pass three more intersections and turn left, and so on. What’s more, the same series of simple instructions works for every maze and every map.
 

How does the new algorithm work? Reingold’s method of reducing the memory load is as surprising as it is counterintuitive. His first step is to further complicate the maze, adding new paths and intersections. These are laid out in such a way as to convert the original maze into a type known to computer scientists as an “expander graph.” The algorithm for finding a route through an expander graph is known to be a simple one that uses little memory. Reingold’s technique conserves the basic layout of the original while building the enlarged maze. Thus, from the route that has been plotted through the expanded maze, it is possible to reconstruct the correct trail through the smaller one, again using minimal memory.
 

Reingold’s work will likely offer computer scientists a new approach to many problems awaiting solution. In particular, it contains vital clues that randomness may not be the only way to spare computer memory. Though randomness is convenient for planning algorithms, Reingold’s innovative work hints at the possibility that for each algorithm that uses randomness, one can find a deterministic one that will carry out the same tasks using a comparably low outlay of memory.

 

Dr. Omer Reingold’s research is supported by the Center for New Scientists. Dr. Reingold is the incumbent of the Walter and Elise Haas Career Development Chair.
 

 
Dr. Omer Reingold. Memory saver
Math & Computer Science
English
  • Algorithm
  • Computer Science and Applied Mathematics
  • Omer Reingold

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