Smelling Like a Rose

English
 
Is the distance between the smell of almonds and that of bananas greater than the distance between the smell of almonds and that of roses? A new method, developed by research student Rafi Haddad under the supervision of Prof. Noam Sobel of the Neurobiology Department and Prof. David Harel of the Computer Science and Applied Mathematics Department, accurately measures, for the first time ever, the distance between different types of odors. Thus, for example, the distance between the smell of almonds and that of bananas is one and a half times greater than the distance between the smell of almonds and that of roses.
 
The new Weizmann technique offers scientists an important research tool for selecting appropriate odorants in olfaction experiments. It also provides the first steps toward understanding the laws that govern the sense of smell.
 
In order to develop their method, the researchers chose about 250 odorants usually used in olfaction experiments and generated for each molecule a long list of chemical characteristics. They then created a multidimensional map of chemical characteristics and placed each odorant in the appropriate location on the map.
 
The scientists used the map to predict neural responses to the 250 odors and compared these predictions to published experimental data on the actual neural responses of various lab animals to these odors. The result: a striking similarity between the predicted calculation and the actual measured responses. These results suggest that the differences between smells are universal and depend on the chemical and physical characteristics of the odor, not on each person’s individual experience or preference – a finding that contradicts the widespread opinion that smell is subjective.  

Prof. Noam Sobel’s research is supported by the Nella and Leon Benoziyo Center for Neurosciences; the J&R Foundation; the Eisenberg-Keefer Fund for New Scientists; and Regina Wachter, New York, NY.

Prof. David Harel’s research is supported by the Arthur and Rochelle Belfer Institute of Mathematics and Computer Science; and the Henri Gutwirth Fund for Research. Prof. Harel is the incumbent of the William Sussman Professorial Chair of Mathematics.
Life Sciences
English
  • Computer Science and Applied Mathematics
  • David Harel
  • Noam Sobel
  • Smell

Order Through Chaos

English

intriguing nanotube shapes

 
Thanks to the rising trend toward miniaturization, carbon nanotubes – being about 100,000 times thinner than a human hair and possessing unique mechanical, electronic, optical and thermal properties – have become the ideal candidates for use as building blocks for nanoelectronic and mechanical devices. But their minuteness and a tendency to clump together make it difficult for scientists to manipulate nanotubes for integration into such nanodevices.

Dr. Ernesto Joselevich, together with Ph.D. student Ariel Ismach and former M.Sc. student Noam Geblinger of the Materials and Interfaces Department, are developing techniques to coax the nanotubes to self-assemble into disentangled, orderly structures – essentially making the nanotubes do the hard work for them.

By applying the universal principle of “order through chaos,” the team has produced nanotubes that are strikingly more ordered and complex than those ever observed before. Their intriguing new type of nanotube structures, which they have termed “serpentines” due to their self-assembly into snake-like and looped configurations, has recently been featured on the cover of the journal Nature Nanotechnology.

Serpentines are common structures on the macroscale in such functional systems as antennae, radiators and cooling elements. Analogously, nanotube serpentines could find a wide range of nanodevice applications – for example, in cooling elements for electronic circuits, optoelectronic devices and power-generating single-molecule dynamos. “But the feature I find most intriguing about these serpentines,” says Joselevich, “is their beauty.”  

An animated movie explaining nanotube serpentine formation can be seen at :

 Dr. Ernesto Joselevich’s research is supported by the Helen and Martin Kimmel Center for Nanoscale Science; the Gerhardt Schmidt Minerva Center on Supramolecular Architectures; and the Wolfson Family Charitable Trust. Dr. Joselevich is the incumbent of the Dr. Victor L. Ehrlich Career Development Chair.
 
A nanotube serpentine observed by scanning electron microscopy
Chemistry
English
  • Carbon nanotubes
  • Ernesto Joselevich
  • Materials and Interfaces

Ancient Throwback: New Technology

English
Unknown Object
 
 
biosensor reveals riboswitch activity
 
 
 
 
Today the management “posts” in the cell are occupied by proteins; but eons ago, when single-celled organisms were beginning to make their mark on Earth and life was simple, the living world might have been an “RNA world.” Recent findings suggest that RNA molecules, single strands of nucleic acids that are far less sophisticated than proteins, are capable of performing many of the cell’s main regulatory functions.
 
Riboswitches, discovered several years ago in bacteria, are segments of RNA that can bind to certain substances, thereby regulating the levels of these substances in the cell. Only one riboswitch has so far been found in higher organisms: The thiamin (vitamin B1) riboswitch regulates thiamin biosynthesis in numerous organisms that produce this vitamin – from the most ancient bacteria to highly developed plants. Dr. Asaph Aharoni and Samuel Bocobza of the Plant Sciences Department investigated this lone plant riboswitch. The scientists revealed the mechanism by which the riboswitch senses the presence of thiamin in the cell nucleus and makes sure the levels of this essential vitamin are neither too high nor too low by turning its production on or off as needed.
 
They may be ancient mechanisms, but riboswitches could be the basis of sophisticated future biotechnologies. Aharoni and Bocobza engineered reporter genes – genes that glow in fluorescent colors under the microscope when activated – that responded to thiamin levels as the riboswitches did. When inserted into plants, these reporters lit up whenever thiamin levels fell. This sort of reporter gene-riboswitch combination could pave the way to the design of live biosensors for all sorts of applications.  
 
Dr. Asaph Aharoni’s research is supported by the Sir Charles Clore Research Prize; the William Z. and Eda Bess Novick New Scientists Fund; the Henry S. and Anne Reich Family Foundation; Sir Harry Djanogly, CBE; Mrs. Louise Gartner, Dallas, TX; Mr. and Mrs. Mordechai Segal, Israel; and the estate of Fannie Sherr, New York, NY. Dr. Aharoni is the incumbent of the Adolpho and Evelyn Blum Career Development Chair of Cancer Research.
 
Biosensor makes the plant glow (right) when thiamin levels drop
Environment
English
  • Asaph Aharoni
  • Plant Sciences
  • RNA
  • Sensor

Deadly Repeats

English
Huntington’s disease is a genetic time bomb. Programmed in the genes, it appears at a predictable age in adulthood, causing a progressive decline in mental and neurological function, and finally death. There is, to date, no cure. Huntington’s, and a number of diseases like it, collectively known as trinucleotide repeat diseases, are caused by an unusual genetic mutation: A three-letter piece of gene code is repeated over and over in one gene. By the number of these DNA repeats, one can predict, like clockwork, both the age at which the disease will appear and how quickly it will progress. But what is the mechanism behind this remarkable precision?
 
Shai Kaplan in Prof. Ehud Shapiro’s lab in the Biological Chemistry, and Computer Science and Applied Mathematics Departments, realized the answer might lie in the buildup of mutations that occurs in our cells throughout our lives. The scientists realized that the longer the initial disease sequence, the greater the chance of additional mutations. In this manner, the genes carrying the disease code might accumulate more and more DNA repeats over time, until some critical threshold is crossed.
 
Shapiro, Kaplan and Dr. Shalev Itzkovitz of the Computer Science and Applied Mathematics Department have created a computer simulation that predicts, from the given number of genetic repeats, both the age of onset and the disease progression. The new disease model appears to fit all of the facts and to provide a good explanation for the onset and progression of all of the known trinucleotide repeat diseases. This explanation may, in the future, point researchers in the direction of a possible prevention or cure. 
 
Prof. Ehud Shapiro’s research is supported by the Clore Center for Biological Physics; the Arie and Ida Crown Memorial Charitable Fund; the Cymerman - Jakubskind Prize; the Fusfeld Research Fund; the Phyllis and Joseph Gurwin Fund for Scientific Advancement; the Henry Gutwirth Fund for Research; Ms. Sally Leafman Appelbaum, Scottsdale, AZ; the Carolito Stiftung, Switzerland; the Louis Chor Memorial Trust Fund; and the estate of Fannie Sherr, New York, NY. Prof. Shapiro is the incumbent of the Harry Weinrebe Chair of Computer Science and Biology.
Math & Computer Science
English
  • Biological Chemistry
  • Computer Science and Applied Mathematics
  • DNA
  • Ehud Shapiro
  • Genetic disease

One Hundred Times Stronger

English
Natural interferon is widely used to treat a number of different cancers, but its effectiveness is rather modest. Weizmann Institute scientists have now succeeded in engineering a new version of interferon whose activity is 100 times stronger than that of the natural molecule.
 
Prof. Gideon Schreiber of the Institute’s Biological Chemistry Department was originally interested in a basic research question concerning interferons: How do these proteins produce two different kinds of effects inside the cell – either serving as the body’s first line of defense against viral infection or inducing programmed cell death, called apoptosis? Schreiber revealed that the different types of activity stem from the way interferon binds to its receptor. Moreover, his team identified the precise amino acids and structural features that affect the binding.
 
The scientists then created versions of interferon with different degrees of binding ability and different types of activity: They manipulated the interferon-receptor bond by replacing various amino acids in the interferon’s binding site and then testing the resulting interferon versions. Using this approach, they managed to create an interferon molecule, called YNS, that binds to cellular receptors much more strongly and, in a laboratory dish, is 100 times more effective than natural interferon at triggering the death of cancer cells. The scientists then found that the YNS molecule effectively eliminated human breast cancer cells in laboratory mice, while the natural interferon did not.
 
 
Yeda Research and Development Company, the Institute’s technology transfer arm, has patented the YNS molecule. If the new interferon proves sucessful ateliminating cancer cells in humans, it could be developed into an effective anti-cancer drug.  
 
Prof. Gideon Schreiber’s research is supported by the Clore Center for Biological Physics; the Helen and Milton A. Kimmelman Center for Biomolecular Structure and Assembly; and Mr. and Mrs. Yossie Hollander, Israel.
Life Sciences
English
  • Biological Chemistry
  • Cancer
  • Gideon Schreiber
  • Interferon
  • Yeda

The Weak Link

English
MMP-9 structure reveals flexible link

 

When cancer cells metastasize or tissues become damaged through inflammation, it’s likely that enzymes called matrix metalloproteinases (MMPs) are involved. This family of enzymes cuts through various bodily materials, including the tough collagen fibers that hold our tissues together.
 
One member of the family in particular – MMP-9 – is often produced by migrating cancer cells and in certain autoimmune diseases, and scientists have long believed that finding a way to inhibit its activities might be useful for treating these diseases. A team led by Prof. Irit Sagi of the Structural Biology Department in the Faculty of Chemistry has now employed an unconventional combination of techniques to reveal the structure of the entire MMP-9 protein. The team included Gabriel Rosenblum of the Structural Biology Department, Drs. Phillippe Van den Steen and Ghislain Opdenakker of the University of Leuven, Belgium, and Dr. Sidney Cohen of the Institute’s Chemical Research Support.
 
Their findings revealed a linker whose extreme flexibility and contortions “would impress even a swami yogi,” in the words of a scientific reviewer. The distinctive MMP-9 linker may turn out to be its Achilles’ heel: The team has already designed a molecule that binds directly to this domain to neutralize its activity, and Yeda, the business arm of the Weizmann Institute, has applied for a patent for this molecule.  
 
Prof. Irit Sagi’s research is supported by the Avron-Wilstaetter Minerva Center; Mr. and Mrs. Michael Ambach, Boca Raton, FL; and the estate of David Turner. Prof. Sagi is the incumbent of the Maurizio Pontecorvo Professorial Chair.
Structural model of an MMP-9 enzyme
Chemistry
English
  • Enzyme
  • Irit Sagi
  • Protein structure
  • Structural Biology
  • Yeda

Two-Way Stretch

English
cells react to stretch
 
 
Biomaterials combine living cells with an artificial gel-like medium. Such materials are being explored for use, among other things, in synthetic replacement tissues and organs. But some traits of biomaterials have been puzzling scientists for many years. Prof. Samuel Safran and Dr. Rumi De of the Institute's Materials and Interfaces Department, together with Dr. Assaf Zemel, formerly a postdoc in Safran's group and now at the University of California, Davis, have proposed a solution to one of those puzzles.
 
When the gel is stretched, say by pulling on either end, the cells respond by reducing the stress on their connections to the medium. But the timing of that stretch affects the way the cells orient themselves: When the gel is stretched slowly, the cells align parallel to the direction of the externally imposed stretch, but if it's stretched quickly, that alignment is nearly perpendicular.
 
What causes the difference? The scientists propose that in both cases a cell adjusts itself to maintain an optimal amount of stretch in the medium. In slow stretching, the cells, which tend to contract, have time to align themselves and take the steps needed to counteract the external stretch, as though steeling themselves for a tug-of-war. When the stretching is quick, however, they don't have enough time to develop this careful balancing of forces. Turning about 90 degrees effectively takes them out of the game of tug-of-war, since the medium cannot pull on the cells in this position.
 
This research, which appeared recently in Nature Physics, may aid in designing and processing biomaterials with specific properties, and may have implications for research in wound healing and muscle growth, as well as elucidating the behavior of cancer cells and more.
 
Prof. Samuel Safran's research is supported by the estate of David Turner. Prof. Safran is the incumbent of the Fern and Manfred Steinfeld Professorial Chair.
 
Top: The cell pulls to maintain a fixed stretch in the gel. Middle: If the gel is externally stretched, the cell can reduce the force it exerts. Bottom: If the gel is alternately stretched and relaxed, the frustrated cell cannot "decide" how much force to exert. This results in the cell orienting perpendicular to the stretch direction
Chemistry
English
  • Biophysics
  • Cell
  • Materials and Interfaces
  • Samuel Safran

Help on the Way

English
In infection, the body calls out the "paramedics" – the white blood cells, or leukocytes – to come to the rescue. Chemical substances called chemokines put through the emergency call and direct leukocytes to the right location.
 
Leukocytes maneuver their way through the body's transport system – the blood vessels – but they must be able to exit at the site of the infection. The chemokines help out by activating molecules on the leukocyte surface called integrins – sticky proteins that act as brakes on the circulating cells and guide them out of the blood vessels.
 
Prof. Ronen Alon of the Immunology Department has now discovered some previously unidentified links in this process. One of these is a biochemical switch that acts on the integrins, stabilizing them in a configuration that enhances their adhesiveness. Another is the mechanical force created by the blood flowing against the vessel wall, otherwise known as shear force. Alon, postdoctoral researcher Dr. Eilon Woolf and colleagues discovered that shear force, which, intuitively, should disrupt cell adhesion, is in fact crucial to initiating the series of events in which the sticky integrin molecules bring the leukocytes to a halt and facilitate their exit from the blood vessels. In research published recently in Nature Immunology, the team showed that if either of these links is missing, the leukocytes can't make their way from the blood to the scene of the infection.
 
Several years ago, a rare disease caused by a defective gene for leukocyte adhesion, called LAD-III, was identified by Dr. Sara Feigelson and Ronit Pasvolsky of Alon's lab, in collaboration with Prof. Amos Etzioni, Head of the Pediatrics Department of the Meyer Children's Hospital in Haifa. This severe immunodeficiency syndrome is associated with a higher than usual white blood cell count in the blood and severe bleeding disorders. Alon's team, together with colleagues in the Molecular Genetics Department and Biological Services unit recently conducted a genetic analysis on samples from LAD-III patients, and their research revealed that one single protein is faulty in this disease. This protein, found in many cell types, determines the biochemical switch that's turned on by the chemokines to activate integrin adhesiveness on all white blood cells – substantiating the team's earlier findings on the importance of each link in the chain of events that directs the white blood cells out of the blood vessels to the sites of infection.
 
Prof. Ronen Alon's research is supported by the Belle S. and Irving E. Meller Center for the Biology of Aging. Prof. Alon is the incumbent of the Linda Jacobs Chair in Immune and Stem Cell Research.
Life Sciences
English
  • Immunology
  • Ronen Alon
  • White blood cell

Keeping the Memories Alive

English
Are our memories recorded in a one-time physical change, like writing permanently on a clay tablet? Prof. Yadin Dudai, Head of the Weizmann Institute's Neurobiology Department, and his colleagues recently discovered that the process of storing long-term memories is highly dynamic, sustained by a molecular machine that must run constantly. They showed that stopping the machine even briefly can erase some types of long-term memories. These findings, which appeared recently in Science, may pave the way to future treatments for memory problems.
 
Dudai and research student Reut Shema, together with Todd Sacktor of the SUNY Downstate Medical Center, trained rats to avoid certain tastes. They then injected a drug to block a specific protein into the taste cortex – an area of the brain associated with taste memory. They believe that this protein acts as a miniature "machine" that keeps memory running by actively maintaining physical, learning-induced changes in the synapses – the conduits for signals between nerves. The scientists reasoned that blocking the protein would reverse those changes. Regardless of the taste the rats were trained to avoid, they forgot their learned aversion after a single application of the drug into the brain, and the signs so far indicate that the unpleasant memories of the taste had indeed disappeared. This is the first time that memories were shown to be susceptible to erasure long after their formation.
 
"This drug is a molecular version of jamming the operation of the machine," says Dudai. "When the machine stops, the memories stop." These findings raise the possibility of developing future, drug-based approaches for boosting and stabilizing memory.
 
Prof. Yadin Dudai's research is supported by the Norman and Helen Asher Center for Brain Imaging; the Nella and Leon Benoziyo Center for Neurological Diseases; the Carl and Micaela Einhorn-Dominic Brain Research Institute; the Irwin Green Alzheimer's Research Fund; and the Sylvia and Martin Snow Charitable Foundation. Prof. Dudai is the incumbent of the Sara and Michael Sela Professorial Chair of Neurobiology.
Life Sciences
English
  • Learning and memory
  • Yadin Dudai