A Short Day on Saturn

English
If you could jump a spaceship out past Mars and Jupiter to Saturn, pass by its rings and somehow park on the planet’s gaseous surface, how long would your day be there? This question, surprisingly, has not been precisely answered until now. The measurements – including those from the NASA Cassini spacecraft that is currently orbiting Saturn – have disagreed with one another, so they could be off by as much as a whopping 15 minutes. That range, says Dr. Yohai Kaspi of the Weizmann Institute’s Earth and Planetary Sciences Department, is a relatively large discrepancy for a giant planet with a day length – the planet’s rotation period – of just around ten and a half hours. Kaspi and his colleagues have now introduced a new method, which was published this week in Nature, that they used to accurately fix this fundamental value. Among other things, it can help scientists better understand the physical processes that shape Saturn and other planets like it. 

 

A day on Saturn
 
Determining the exact rotation period of Saturn has been problematic because two of the more common methods are useless there. The planet is mostly gas, so its surface features – windy streams that move at varying speeds – conceal the turning of the planet’s solid core. Another method, used for planets like Earth and Jupiter, is to measure how the magnetic pole rotates around the true pole; but on Saturn these two poles are aligned, so that rotation can’t be measured. Until now the measurements of Saturn’s rotation period have relied on radio emissions tracked by nearby spacecraft.

Kaspi and research scientist Dr. Eli Galanti, working together with Dr. Ravit Helled of Tel Aviv University, devised a way to calculate the planet’s rotation period based on measurements of its gravitational fields. “This method,” says Kaspi, “basically works backwards from the gravitational field and shape of the planet.”  As a large body, eg., a planet, spins, its shape flattens out a bit, gaining a sort of “belly” at its middle, he explains. The faster it spins, the more pronounced this belly will be. The resulting redistribution of the planet’s mass, in turn, creates fluctuations in the gravitational field of the planet. The gravitational field has been well measured and calculated, both by planetary missions and by telescope data; thus the gravitational field measurements could be used to uncover the missing figures for the rotation that produced them.  
 
 
The difficulty, says Galanti, was in the math. The equations originally contained too many variables to yield useful answers. So the team worked out a statistical method that reduced the uncertainties in the numbers. They then tested their method using figures for the gravitational field of Jupiter – a planet for which the rotational period has already been precisely calculated by the magnetic pole rotation method. When the gravitational field method yielded a number that precisely matched the known length of a day on Jupiter, the team applied it to Saturn’s rotation.
Dr. Yohai Kaspi
 
The figure they came up with matched the faster measurement, fixing the length of a day on Saturn at ten hours, 32 minutes. The uncertainty is now around 45 seconds – compared to the previous 15 minutes. Having a precise figure for Saturn, says Kaspi, will help researchers create models of how the planet formed and what goes on deep beneath its cloudy outer surface; but it will also provide another tool to help fix the rotation periods of other, farther out planets in the solar system and even beyond.
 
Dr. Yohai Kaspi's research is supported by the the Helen Kimmel Center for Planetary Science.
 
 
Illustration of Saturn
Space & Physics
English

The Coral Sweepstakes

English

04-11-2014

 

coral sweeping
Vortical ciliary flows enhance the exchange of oxygen and nutrients between corals and their environment. Paths of tracer particles between two adjacent polyps of the reef coral Pocillopora damicornis, spaced about 3 mm apart, are color coded to reflect local flow velocity

 

 
 

Corals get their oxygen and nutrients from the water that flows around them. Research in the group of Dr. Assaf Vardi of the Weizmann Institute’s Plant and Environmental Sciences Department and Prof. Roman Stocker of the Massachusetts Institute of Technology (MIT) now reveals a surprise dimension of reef-bound coral life: The polyps (corals are actually a symbiotic combination of polyp and alga) use their cilia – tiny hairs covering their surface – to sweep the surrounding water. This sweeps in nutrients as well as sweeping away waste products.

 

 

 

 

The motion of tracer particles (1m diameter, imaged by dark field microscopy; 4x magnification) reveals the rapid vortical flows driven by cilia covering the surface of a reef-building coral. By actively mixing their boundary layer, corals enhance the exchange of oxygen and nutrients with the environment

 

By adding tracer particles to the corals’ environment and filming them with high speed videography and powerful microscopy techniques, Dr. Orr Shapiro of Vardi’s lab – at the time a guest of Stocker’s group – and Dr. Vicente Fernandez of Stocker’s lab captured, for the first time, the polyps’ cilia in action.


The findings, which appeared in the Proceedings of the National Academy of Sciences (PNAS), help explain the long evolutionary success of corals and give some hope for their future.

 

 

 

Coral Cilia. Cilia covering the surface of reef-building corals beat synchronously to drive rapid vortical flows (150x magnification)

 

 

 

Dr. Assaf Vardi’s research is supported by the Human Frontiers Science Program (HFSP); Roberto and Renata Ruhman, Brazil; Selmo Nussenbaum, Brazil; the Brazil-Israel Energy Fund; the Lord Sieff of Brimpton Memorial Fund; the European Research Council; and the estate of Samuel and Alwyn J. Weber. Dr. Vardi is the incumbent of the Edith and Nathan Goldenberg Career Development Chair.

Environment
English

The Scanners’ Story

English
 
Scanning, circa 1963. Image: Weizmann Institute Archives
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Once upon a time, before the days of computers on every desktop and in every bag, there were scanners. These were people, up to twenty at a time, who worked at scanning the results of physics experiments conducted in the particle accelerators of the US and Europe. From the 1960s until 1980, the scanners, mostly women, toiled day and night in the physics department of the Weizmann Institute of Science. Their job: to help discover and study the properties of subatomic particles and the forces that act between them.

“We all started out as young single women,” says Helen Katz, “and by the time we finished, we were all married and mothers. Now, as we are retiring from the Institute, many of us are grandmothers.” “It wasn’t that men weren’t hired,” according to Nitzhona Akshuti. “It was just that the women were the ones who stayed.” The story of the Weizmann scanners is more than the story of a group of hired workers who were trained to identify the tracks of elusive particles in image after image. It is also the story of a group of women who became fast friends over the years, celebrating marriages and births together and helping one another through hard times. As some point, they gave themselves the name “the scanners” (scanneriot in “Hebrish”). Even today, they are happy for an excuse to get together to exchange news and talk about their scanning days.
 
 
Find the event: bubble chamber frame
 

Beginning of an era


Scanning, as a job, began in the 1950s, when particle physicists began using a new apparatus to uncover the secrets of the particles locked up inside atoms: the bubble chamber. The late Prof. Gideon Yekutieli of the Weizmann Institute wrote in 1963: “Now, the era of the photographic plate is over, and a new one has begun: that of the bubble chamber. The laboratory landscape has changed accordingly. Microscopes and photographic emulsions have vanished. In their place have appeared scanning tables and special apparatus for measuring photographs, cine-camera spools and IBM punch-cards.”

Bubble chambers were large containers of liquid – usually hydrogen – kept under pressure just below the boiling point. The containers were attached to accelerators – for example, the SLAC linear accelerator at Stanford. In these accelerators, beams of such particles as electrons were shot at high energies through a target, causing new particles to come into existence. Those particles left tracks of tiny bubbles of heated gas as they sped through the liquid hydrogen. Each particle left a signature track, depending on its energy, mass and lifetime. Most of the particles were unstable: Some broke down into other particles within mere fractions of nanoseconds. So a new particle might be identified by the tracks of its secondary particles.

The bubble chambers produced moving films of the particle events in 3-D – that is, special high-speed cameras filmed the experiments from three angles. The results were then shipped to the Weizmann Institute in giant rolls of film that had to be analyzed, frame by frame, from all three angles, often two or three times to be sure that any findings were correct.
 

 

Fermilab bubble chamber
 

A demanding task


To be a scanner, one had first to travel to Jerusalem and pass a series of tests in the Hadassah Institute. “With all the tests they gave us, we thought we were being tested for air force pilot training,” says Anat Shaibin. Hand-eye coordination was important, as was attention to detail, good eyesight and the ability to work well in a team. Tova Presman remembers applying for the job when she was a new immigrant and still having difficulty with the Hebrew instructions. Helen, who was also undergoing the tests, helped her out.

Scanning was conducted in a darkened room; the scanners viewed their frames on special tables or, later, screens. Operating the apparatus took some skill and a certain amount of coordination: foot pedals and stick controls were needed to move the frames along, and coordinates had to be carefully noted. In less than a second, a practiced scanner could determine whether there were any particle tracks of interest among the patterns of lines and swirls on the image and move on. Some 35 years later, they can still hear the swooshes and clicks of the frames spooling past.

Yekutieli reported in the summer of 1963 that the Weizmann team had received 30,000 frames. The scanning capacity of one table, he said, was 200 pictures a day. Three days’ worth of experimental results – some 60,000-100,000 images – translated, back then, into two years of work for the scanners. With time, new equipment improved the scanners’ efficiency, and extra shifts were added to speed up the process and make better use of the equipment. By the time that Yaffa Berko was hired – in 1975 – some of the measuring was no longer done by hand but passed on to the computer operators. Still, the main job – scanning frame after frame for signs of the desired particle trace – remained a demanding yet repetitive task.

 

Prof. Uri Karshon, 1983
 
For many years, Prof. Yehuda Eisenberg headed the Weizmann physics group that employed the scanners. “He always treated us with respect, as a part of the team,” say the women. “We never felt that we had a different status than those with more education.” In fact, education and learning were no less important to the scanners than to the top physicists. Every Thursday the scanners would stop their work for a few hours and meet for lectures, including talks on the physics that produced the lines and circles on the frames.


The particle zoo


Prof. Uri Karshon began his career in physics around that time, getting his PhD at the Weizmann Institute in 1967. In that period, he recalls, the field seemed to be a “zoo of particles.” The underlying theory that would hold them together – now known as the Standard Model of Particle Physics – was still being hammered out. The Israeli scientists, as members of small international research groups, would travel to Stanford, Brookhaven in New York, Fermilab near Chicago and CERN in Europe to conduct the particle-beam experiments. In time the Standard Model solidified and became accepted. “In all the physics experiments done since, including the recent ones conducted at the giant LHC facility at CERN, nothing has been discovered that contradicts or disproves that model,” says Karshon. Among the theorists working on the Standard Model was Israel’s Prof. Yuval Neeman, who played a major role in laying the foundations of modern particle physics.

The particles that popped up in the Institute scans included such particles as pi- and K- mesons – particles made up of a quark and an antiquark; and resonances – particles that are extremely short-lived, even for the subatomic products of particle collisions. Karshon credits the scanners with exceptionally good work. As an example, he points to his own doctoral research, supervised by Prof. Gideon Alexander, which involved the collision of a neutral particle with a proton. Since neutral particles do not leave tracks in the bubble chamber, the resulting trace in the images was a very brief, tiny blip “appearing out of nowhere,” produced by the scattered proton, followed by two charged particles that decayed from the neutral one. These were very hard to see; but the resulting work, he says, was important. That paper is still cited today – a rarity in a scientific field that has seen so many changes. “It’s safe to say that without the work of the scanners, what I accomplished in my PhD research would not have been possible,” he says.  
 
(l-r) Tova Presman, Anna Weisman, Helen Katz, Gila Udi, Yaffa Berko, Anat Shaibin, Nitzhona Akshuti and Geula Issachar

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Sisters


In 1971, Hana Goldshtein was 19 years old. That was the year she came with her parents to Israel from Lithuania, which was then a part of the USSR. She had dreamed of becoming a musical conductor and had even started her studies, but now she needed to work and help support her family. Her parents’ only daughter, she recalls feeling isolated and lonely in her new home. But a short time after Hana began working in the scanning room, Nitzhona, whose family originally came from Yemen, “told me she was going to adopt me as a sister. This group of women has been family to me ever since. We helped one another through all sorts of hard times, and we are still close – sometimes closer than our real families,” says Goldshtein.

Anna Weisman also came to Israel from the former Soviet Union. Although she had an advanced degree in biochemistry, the only work she could find in the beginning was scanning. The women in the group, however, decided that she should have a job in her profession, and encouraged her to move on. Together, they found her a position in one of the Weizmann Institute labs, where she continued to work until recently.
 
 
(l-r) Hana Goldshtein, Anat Shaibin and Prof. Giora Mikenberg building detectors for CERN
 

Marvelous machines


Yekutieli wrote, back in 1963: “One day we hope to scan automatically… When we can teach the computer to detect forms and distinguish efficiently among them, a new chapter will open in data-processing… With the merest flick of a finger, we will start the operation, and after days, weeks or months, our marvelous machine will eject a completely finished work – all set for print.”
 
Indeed, during the 1970s, not only were computers starting to replace humans in jobs such as scanning, but particle accelerator technology was also changing. Instead of beams of particles aimed at a target, the new accelerators held two beams traveling in opposite directions, generating high-speed particle collisions. Instead of bubble chambers and film, new types of particle detectors were connected directly to computers that could automatically record collision events. This collider design is basically the same as the one used to build the LHC – the Large Hadron Collider – at CERN under the France-Switzerland border, which recently gave us proof for the existence of the Higgs boson, the final “missing piece” of the Standard Model.

As the scanning room was closing down in 1980, new opportunities were opening. The LEP – Large Electron-Positron Collider – a 27-km-long underground ring for particle physics experiments – was being planned. The Weizmann Institute was in on the project from the beginning, taking on the design and construction of the particle detectors. The scanning team members were offered jobs building the detectors.

Hana and Anat were the first to make the move, helping to build the prototypes. They were later joined by several of the others. “I started as a scanner, but I became a welder and ‘engineer’,” says Geula, with some pride. Other members of the group spread out over the Weizmann Institute, many of them going on to various administrative positions. Now, most of them have retired, but they still feel the Weizmann Institute is their second home. They speak of a sense of belonging – both to the Institute and to the work. Through the long hours of scanning, they say, they took pride in the importance of the work – in the contribution they were making to the advancement of science. Nitzhona has even, on a trip to the US, gone to visit the SLAC facility at Stanford, to see where all those frames she scanned originated. And they point out that the experience of scanning had some positive effects on their daily lives. “For instance, we are all better drivers,” says Geula. “We immediately pick out the important details in our field of vision.”

Today, says Karshon, another era may be closing for particle physics, with the final piece of the Standard Model in place, but a new one will be opening, maybe even when the LHC starts up again. “We know there are other particles out there – beyond those in the Standard Model – that we can’t yet see,” he says. Hana Goldshtein is one of the few former scanners remaining at the Institute. She still works in the Mexico building on campus, where particle detectors are today being assembled for the LHC, which replaced the LEP collider in its tunnel – though she has moved on from assembly to administration. Among other things, she is helping work out the details for a new type of detector they are building. “But that,” she says, “is another story. When I think back on my days as a scanner, even with all of the hard parts – those were the best days of my life.”  
scanners- then and now
 
 
 
 
 
(l-r) Tova Presman, Anna Weisman, Helen Katz, Gila Udi, Yaffa Berko, Anat Shaibin, Nitzhona Akshuti and Geula Issachar
Space & Physics
English

Someone to Operate It and a Place to Put It

English

 The first electron microscope (Saul, RCA – EMU - 2A). (l-r) John Fany, Prof. David Danon and Dr. Yehuda Marikovsky, 1956

      

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Danon and Marikovsky


On January first, 1955, two new employees showed up at the Weizmann Institute. The two were fresh out of the air force, having served at the Tel Nof air base near Rehovot. Prof. David Danon, a medical doctor, had been the first commander of the air force medical rescue unit and Dr. Yehuda Marikovsky had been in charge of the clinic’s lab.

Marikovsky was born in Czechoslovakia in 1924 with the name Yehuda Morganbesser. During World War II, he was sent to the Zilina concentration camp in Slovakia, where he worked in the clinic. Afterward, he was transferred to the Vyhne work camp, which was liberated by the partisans in 1944. Yehuda joined the partisans, obtaining forged documents with the name Marikovsky – a name that helped him survive the war. When the State of Israel was founded, Marikovsky heeded the call for volunteers to build the new country’s air force. He first trained in Czechoslovakia, arriving in Israel in February, 1949, with his new wife Tzipora.

Danon and Marikovsky met in Tel Nof: Danon was called up in 1953. He had been obliged to leave Palestine (he had immigrated at age four from Bulgaria) because of his prominent role in the Lehi anti-British activities. His parents, both doctors, registered him for medical school in Geneva, putting an end to his dreams of becoming a painter. Danon turned to biomedical research; in Switzerland he began working with electron microscopes, inventing a device to slice samples very thinly for observation. He completed his studies with honors, and his doctoral thesis was awarded first prize from the Faculty of the University of Geneva Medical School.    

Word of the talented young air-force doctor reached the ears of the Weizmann Institute’s Prof. Ephraim Katzir. Katzir invited Danon to get the Institute’s electron microscope unit up and running. Danon agreed and asked Marikovsky to join him there.
 
 
Second electron microscope (Bathsheba, RCA-EMU-3G). (l-r) Yael Frei, Oded Grenberg, Miriam Shamir, Rita Aronov, Joseph Binder and Dr. Yehuda Marikovsky, 1963

Saul and Bathsheba


In a letter written by Chaim Weizmann to Prof. Ernst Bergmann in 1945, he listed two conditions necessary for an electron microscope: someone who knows how to operate and maintain it, and a place to put it.
 
The original microscope was donated by William S. Paley, CEO of CBS, who obtained it from David Sarnoff, CEO of RCA. Both of them were old acquaintances of Weizmann’s from his days as president of the World Zionist Organization. In 1952, Sarnoff would be named an Honorary Fellow of the Weizmann Institute of Science.
 
The minutes of planning committee for the Chaim Weizmann Institute in December, 1945, reveal that 600 sq m of space in the Ziskind building would be allotted to the electron microscope. The microscope, itself, arrived in Israel in 1949. It was the first commercial model sold by RCA; and it had an angular separation of 50 angstrom. The microscope fell under the aegis of Prof. Ephraim Frei; it was used, among other things, to research the “Weizmann microbe.”  

Danon called the microscope “Saul,” after the first king of Israel. And, indeed, the microscope was a bit of a despot, making demands on the scientists’ skills, not to mention their work hours. For example, when instruments in the lab of Prof. Gerhard Schmidt created magnetic fields that disturbed the operation of the microscope’s vacuum pumps, Danon and Marikovsky found themselves working at night. In his free time, between preparing samples, Danon would play his guitar, sometimes accompanied by Schmidt on a flute.

When Danon and Marikovsky needed new bell jars for the vacuum, they conscripted the electrician, Yaakov Lipkin, to help jury-rig glass containers. They replaced the thin gold wire needed for the process of shadow casting with nickel-chrome wire from an iron. This substitution worked so well, they ended up publishing three technical papers on the subject. Meanwhile, Danon was building an even better device for thinly slicing the samples.
 
 
 
electron microscope moving day, 1963
 
With the advance of time and science, the Institute needed a newer model. William S. Paley once again donated the microscope, also manufactured by RCA. It was named Bathsheba, a play on the Hebrew word for “seven,” because the resolution of the new microscope was a mere seven angstrom.

When the Ullman building was completed in 1963, Bathsheba was moved there. Photos of the move reveal that the electron microscope – the height of technology – was borne to its new home by an old-fashioned but dependable horse and cart. Bathsheba, of course, has been replaced several times over by newer and younger models, but she was the last to be named. Nowadays, the electron microscopes are the responsibility of the Chemical Research Support Department.

Marikovsky enrolled in the Feinberg Graduate School in 1967, completing his doctorate in 1973 with work under Danon on the aging process in red blood cells. After a stint at Tufts University Medical School in Boston, he returned to the Weizmann Institute in 1977 to work with Danon. Danon’s research into the function of macrophages in healing would lead to the development of a treatment for pressure wounds in geriatric patients.

Though he has retired, Marikovsky is still engaged in active research, advising and working with the lab group of Prof. Yechiel Shai. His son, Moshe, has followed in his father’s footsteps, completing a PhD in the lab of Prof. Ruth Arnon. His daughter, Ita Hebel, is a child therapist and educational consultant.  
 
 
 
 The first electron microscope (Saul, RCA – EMU - 2A). (l-r) John Fany, Prof. David Danon and Dr. Yehuda Marikovsky, 1956
Life Sciences
English

Remembering in Time

English

Dr. Yaniv Ziv

If you try to recall the details of yesterday’s dinner, they are probably still vivid in your mind. But recalling the dinner you had a few days ago takes much more effort, even if you’d been dining in the same place and in the same company. What neural mechanisms make the newer memory clearer and the older ones vague and harder to retrieve? In more general terms, what happens to memories stored in the brain over time, sometimes over a lifetime? How are they affected by the passage of time, new experiences or disease?


These are the kinds of questions investigated by Dr. Yaniv Ziv, who recently joined the Weizmann Institute’s Neurobiology Department as a senior scientist. Ziv is focusing on the hippocampus, the brain structure that forms and stores the memories of events – episodic memory – as well as playing a central role in spatial orientation. This structure, located deep inside the brain under the cortex, has recently been the site of one of the most fascinating discoveries in modern neuroscience: Contrary to accepted dogma, new neurons are born in the adult human brain all the time. In fact, new neurons are estimated to be generated in the human hippocampus at the rate of about 700 a day. One of Ziv’s research goals is to clarify the role that these neurons play in the processing of memory.


To investigate memory over the long term, Ziv is taking advantage of optical imaging, an advanced technique that involves recording brain activity on video via a microscope.  During his postdoctoral research at Stanford University, he developed an optical imaging approach that has for the first time made it possible to accomplish a challenging task: monitoring the activity of large numbers of neurons deep within a living brain over a long period of time. The approach combines three novel technologies: a miniaturized fluorescence microscope that can be mounted like a helmet on the head of a freely-moving mouse; ultra-thin, rod-shaped implantable lenses that serve as micro-endoscopes for imaging deep-brain structures; and genetically engineered neurons that emit fluorescent light, whose varying intensity serves as an indicator of neuronal activity.
 

neurons

 

While at Stanford, Ziv used the system to perform a study in which he tracked the activity of thousands of so-called “place cells” in the hippocampus of mice over the course of several weeks as they explored a maze. As reported in Nature Neuroscience, the study produced a surprising finding: Even as the mice covered the same route in the maze day after day, the route was represented each time in their brain by a different subset of neurons – there was only about a 20 percent overlap among the subsets. This finding is consistent with the idea that events occurring in the same place at different times could be encoded differently in the memory. It would explain why we are able to distinguish between memories – for example, between the memory of the walk in the park we took yesterday from that of the same walk a day earlier.


In his new lab at Weizmann, Ziv applies his experimental system to continue examining long-term memory circuits in the hippocampus and study how these circuits are altered by experience and time. In one study, he is exploring how memories are clustered in time, which enables us, for example, to recall all of yesterday’s events as taking place during the same day. He also intends to look into the decline of memory that occurs in neurodegenerative diseases, particularly Alzheimer’s. A great deal has been learned in the past few decades about the genetic mutations and abnormal proteins involved in Alzheimer’s, but it is unknown how these defects affect the storage of information and memory by the brain. Ziv will address the connection between the molecular basis of neural degeneration and alterations in memory processing.


Shared interest


Dr. Yaniv Ziv and his wife Michal share a fascination with the brain: Yaniv seeks to decipher the neural code, Michal is a clinical psychologist. They met while conducting undergraduate studies in biology at the Hebrew University of Jerusalem. Yaniv, who earned his Ph.D. from the Weizmann Institute in 2007, under the guidance of Prof. Michal Schwartz, has joined the Weizmann faculty after conducting postdoctoral research at Stanford University for six years. He and his wife live on the Weizmann campus with their two daughters, aged seven and three.

 

Dr. Yaniv Ziv’s research is supported by the Irving I Moskowitz Foundation.
 

 


 

 
Dr. Yaniv Ziv
Life Sciences
English

A Bridge to Peace

English
 Profs. Lia Addadi and Hasan Dweik
 
 
 
The shortest distance between eastern Jerusalem and Rehovot is not necessarily a straight line; sometimes, it turns out, the optimal route passes through Malta. At least, that has been the experience of Prof. Hasan Dweik, Vice President for Science and Society at Al-Quds University in eastern Jerusalem: He has come to spend a sabbatical at the Weizmann Institute of Science in Rehovot after attending scientific meetings in Malta.

Dweik, a Jerusalem-born polymer chemist educated in the UK, is currently taking part in the development of biomolecular sensors in the laboratory of Prof. Ron Naaman of the Weizmann Institute’s Chemical Physics Department. He had established contacts with Weizmann Institute scientists about ten years ago at one of the international meetings known as the Malta Conferences or, more formally, “Frontiers of Science: Research and Education in the Middle East.” Held every two years, these gatherings bring together about a hundred scientists from more than a dozen Middle Eastern countries, including Israel, Jordan, Iran, Egypt and Saudi Arabia. Topics range from materials science, nanotechnology and medicinal chemistry to environmental issues of concern to the entire region, such as freshwater scarcity, alternative energy and air pollution.

But the goals of the meetings go beyond science. “The idea is for Israelis and Arabs to meet directly without political pressure, using science as a bridge,” says Prof. David Cahen of the Weizmann Institute’s Materials and Interfaces Department, who has participated in all six Malta Conferences to date. “At first I was surprised by the atmosphere of openness, which allowed us to meet scientists from all the countries in the region,” says Prof. Lia Addadi of Weizmann’s Structural Biology Department, another veteran Malta Conference participant.

The Conferences have resulted in long-lasting contacts among scientists, joint Israeli-Arab projects related to water resources and half a dozen students from universities in the Palestinian Authority coming for graduate studies at the Weizmann Institute.
 
Prof. Hasan Dweik of Al-Quds University (left), Dr. Ami Shalit, Director of the Feinberg Graduate School (left, upper row) and students from Al-Quds and Weizmann, participants in the Social Sciences and Humanitarian Affairs Master’s Program of the Sapienza University of Rome, at the Weizmann Institute of Science several years ago
 

 

 
At Dweik’s initiative, a former chemistry student from Al-Quds earned a PhD under the guidance of Prof. Avi Hofstein and Dr. Rachel Mamlok-Naaman of Weizmann’s Science Teaching Department; two other Al-Quds graduates, one in physics the other in computer science, are currently enrolled in the Department. “We want to build up a core of scientists who are good educators in order to create our own faculty of science education,” explains Dweik, who founded the Chemistry and Chemical Technology Departments at Al-Quds and in the past served as the University’s Dean for Science as well as Executive Vice President. Before coming to Rehovot on a sabbatical, he himself had worked with Weizmann Institute scientists on projects in science education, developing informal high-school curricula, textbooks and online courses.  

The inspiration for the Malta meetings came from the Pugwash Conferences, which had facilitated communication between the Western and Eastern blocs during the Cold War, says Dr. Zafra Lerman, President of the Malta Conferences Foundation. A Weizmann Institute graduate in chemistry, Lerman had originally organized the meetings under the aegis of the American Chemical Society, choosing Malta as the venue because of its neutrality and the safety it offers as an island.

To attract participants, Lerman came up with a unique formula: Plenary lectures at the Malta Conferences are given by as many as five or six Nobel laureates in chemistry, physics or medicine. Spouses are not allowed to join, so as not to “dilute” the interactions among the participants. “It’s known in chemistry that if you dilute the solution, the rate of the chemical reaction is reduced,” says Lerman.


Scientists’ responsibility


Weizmann Institute scientists have formed a significant portion of the Israeli contingent at all the Malta Conferences. In addition, at the latest meeting, Malta VI, held in November 2013, one of the Nobel laureate speakers was the Weizmann Institute’s Prof. Ada Yonath.

“I’m a big believer that peace must come from the inside, and scientists have a special responsibility in this respect,” Lerman says. “They enjoy a high status in society, both because governments need them to develop weapons and because they improve humanity’s well-being. They can accomplish so much more than politicians.”

Lerman’s dream is to find sponsors for holding the Malta Conferences more frequently. “Billions of dollars are being spent on weapons of mass destruction,” she says. “A small fraction of that could go so far to engage more Israeli and Arab scientists in collaborative projects in order to create a critical mass that will bring about peace.”

Even though universities from the Palestinian Authority maintain no official contacts with Israeli institutions of higher learning, Palestinian and Israeli scientists can and do collaborate on an individual level. In fact, Dweik believes such contacts are extremely beneficial. “I think that as scientists, we have an important role to play in bringing peace to the region,” he says. “We have this piece of land on which we must live together, and we need to cooperate as neighbors. After all, science knows no borders. No matter where you are studying cancer, developing a new drug or solving an environmental problem, you are working for humanity.”

For Dweik himself, the conflict is anything but abstract: It exacted a tragic toll from him and his family. In 1971, when terrorists threw a bomb at the Jewish-owned “Dolphin” restaurant in eastern Jerusalem, Dweik and his younger brother Hussein, both teenagers at the time, were standing nearby on the pavement outside their father’s Modern Bakery. Hussein was killed in the explosion; Dweik sustained multiple shrapnel wounds all over his body. “That’s the price we pay for failing to resolve the issue,” he says. “As long as the conflict persists, human lives will continue to be lost on both sides.”
 
 
 
Prof. Hasan Dweik of Al-Quds University (left), Dr. Ami Shalit, Director of the Feinberg Graduate School (left, upper row) and students from Al-Quds and Weizmann, participants in the Social Sciences and Humanitarian Affairs Master’s Program of the Sapienza University of Rome, at the Weizmann Institute of Science several years ago
Chemistry
English
Yes

Where Lab and Clinic Meet

English

 

In the midst of a combined clinical and postdoctoral fellowship in the lab of Prof. Brendan Lee in Baylor College of Medicine, in Texas, Dr. Ayelet Erez encountered a case that would set her on her present research path: A child was admitted to the hospital with high blood pressure that did not respond to treatment. That child suffered from a genetic disease; his body lacked an enzyme responsible for the production of a particular amino acid, called arginine. But the connection between the missing enzyme, known for short as ASL, and the symptoms of the disease was a riddle that left the doctors helpless. What took place next illustrates what can happen when science and medicine get together: Erez, who was on a double medical and research track, combined her knowledge from both fields to create a mouse model of the disease.

Dr. Ayelet Erez
 

 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
That is how she discovered a previously unknown function for this enzyme: It is structurally required for the production of nitrous oxide (NO), a biological messenger that plays a role, among other things, in dilating blood vessels and the functioning of the nervous system. She showed that the child’s symptoms were caused by low NO levels in his body – the result of the lack of ASL enzymes. In this case, the path from lab bench to bedside was a short one: The child was treated with a drug supplement containing NO. His blood pressure returned to normal and has remained so until now – for more than three years – and his cognitive abilities eventually began to improve as well. Erez received the William K. Bowes Jr. Award in Medical Genetics, awarded by Harvard Medical School, for this work. “The combination of clinical experience and research enabled me to succeed,” she says, “and it gave me a lot of personal satisfaction – as a doctor, a scientist and a mother.”

Nitrous oxide research goes back to 1846, the year an Italian chemist invented the explosive nitroglycerin. One hundred years later, Ferid Murad, Louis J. Ignarro and Robert F. Furchgott, who received the 1998 Nobel Prize in Medicine for their work, discovered that the body can break down nitroglycerin into NO molecules and that this substance dilates the blood vessels. Since then, mounting evidence points to an important role for this molecule in maintaining blood vessel and nervous system health, but both the mechanisms by which it works and those that regulate its activities have remained unknown. Among the obstacles to research in this area is the fact that three different enzymes are known to produce NO. Results of experimental attempts to genetically manipulate these enzymes, in order to create disease models, for instance, have been inconclusive.

Erez’s solution to this problem is to focus on an earlier stage in the NO metabolic pathway – in which the enzyme she researched at Baylor comes into play. ASL is responsible for arginine production; this amino acid is the raw material that all three NO enzymes process to produce nitrous oxide. Erez later discovered that ASL is also vital for the assembly of the protein complexes needed to produce NO – a role that ranks it as a top regulatory factor for controlling crucial NO levels in the body.
 
bridging the gap
Now, in her Weizmann Institute lab, Erez plans, among other things, to delve deeper into the workings of the ASL enzyme, as well as the metabolic cycles of arginine and NO. The diseases in which disruptions in these metabolic pathways figure include degenerative nerve diseases, kidney failure and cancer, and Erez hopes her findings will contribute to the development of new ways to treat them.


Relevance for real patients


Once a week, Erez forgoes her lab work in the Institute’s Biological Regulation Department to go to the Chaim Sheba Medical Center, in Ramat Gan (near Tel Aviv). There, she spends half a day working in pediatric genetics with families of children whose cancer has a genetic origin. Her work there ties in with another kind of metabolic process she intends to investigate: that which turns a healthy cell into a cancerous one. She believes that by taking both clinical and scientific approaches to fighting disease, the two will end up complementing and strengthening one another. To further this strategy, she and Dr. Eran Elinav of the Immunology Department have started organizing on-campus meetings between researchers and clinical physicians to discuss different topics. “As an MD-Ph.D., my starting and ending point is always the human being; it is important to me that my research questions have relevance for real patients. At the end of the day, over and above the satisfaction of my scientific curiosity, is the fulfillment that comes from understanding a disease mechanism and optimizing its therapy.”


Double studies


Dr. Ayelet Erez was born in Haifa and completed her medical studies at the Technion there. She undertook a residency in pediatrics at Chaim Sheba Medical Center and her doctoral research in cancer genetics was completed at Tel Aviv University while she worked in a pediatric clinic. Her postdoctoral research was conducted at Baylor College of Medicine, in Houston, Texas – a school that allowed her to pursue a medical sub-specialization in clinical genetics along with her postdoctoral work. In 2012, she joined the Weizmann Institute’s Biological Regulation Department.

Erez, her husband, who is a veterinarian, and their two daughters, live on Moshav Bnei Zion, north of Tel Aviv.
 
Dr. Ayelet Erez's research is supported by the Adelis Foundation; Joseph Piko Baruch, Israel; the Dukler Fund for Cancer Research; the Paul Sparr Foundation; and the estate of Fannie Sherr. Dr. Erez is the incumbent of the Leah Omenn Career Development Chair.
 
 

 

 
 
Where Lab and Clinic Meet- Dr. Ayelet Erez Work
Life Sciences
English

A Fossil Comes to Life

English
 
 Hula painted frog. Image: Frank Glaw
       
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The story started with a dead frog. This was no ordinary dead frog, however – it was a preserved specimen of the first species of amphibian ever to have been declared extinct by the International Union for Conservation of Nature (IUCN), back in 1996. After four decades of searching for the Hula painted frog – whose home range had been limited to the boggy Hula Valley of northern Israel – researchers decided the polka-dotted frog had probably been a victim of habitat loss from Israel’s extensive swamp-draining activities in the early to mid-20th century.

When, several years ago, Rebecca Biton and Dr. Rivka Rabinovich of the Hebrew University of Jerusalem wanted to examine the Hula painted frog specimen that had been in their natural history collection since the 1950s, they turned to Dr. Vlad Brumfeld of the Weizmann Institute’s Chemical Research Support. Brumfeld’s lab has advanced micro CT equipment that was suitable for revealing the skeletal structure of the frog in minute detail.
 
 
In the meantime, Dr. Sarig Gafny of the Ruppin Academic Center at Michmoret and Yoram Malka, a park ranger for the Israel Nature and Parks Authority, had refused to believe reports of the Hula painted frog’s demise, and had continued to search for it. In 2011, they found their first living specimen of the supposedly extinct frog, and several more soon followed. A few of the frogs that had died a natural death more recently than the 1950s gave Biton, Brumfeld and their co-workers in Israel, France and Germany additional samples to complete analyzing the morphology of the frog’s skeleton, as well as to investigate the frog’s DNA.
Dr. Vlad Brumfeld
 
The researchers were in for a surprise: In examining the structure of the Hula painted frog skeletons – especially the structure of the head – along with the DNA, they realized that the frog had been wrongly classified when it was first observed by investigators in the 1940s. In fact, the frog is more closely related to fossil amphibians than to any living species. Rather than belonging to the genus of painted frogs Discoglossus, which includes species ranging from Spain to Morocco, it was the sole surviving member of another genus known as Latonia. Its last relatives in the Latonia genus died out around 15,000 years ago. These findings appeared in Nature Communications.
 
 
Since the Hula painted frog was declared extinct, dozens of amphibian species have officially gone extinct and hundreds more are endangered or feared to be extinct. Thus the discovery and identification of the Hula painted frog made it an instant icon – a symbol of hope in the face of the generally bleak outlook for many amphibians around the planet. Not only had it seemingly come back from extinction, but the Hula painted frog turned out to be a true living fossil.
3-D reconstruction of the frog's skull reveals its lineage. Image: Renaud Boistel and Vlad Brumfeld
 

Seeing skeletons


The X-ray microtomography machine in Dr. Vlad Brumfeld’s lab is state-of-the-art, enabling researchers to obtain detailed 3-D images of everything from animal skeletons to microscopic bacteria. The improvement over older models, says Brumfeld, lies in the addition of extra scintillators used to convert X-rays into visual information. These enable scientists to image a range of samples, each at the desired resolution. Recording images while rotating the sample in the chamber of the machine makes it possible to produce 3-D images of thick, opaque objects, thus revealing tiny details – down to just a few microns – not seen through other methods.

To obtain the detailed, 3-D image of the Hula painted frog skeleton, Brumfeld used a technique he had developed together with Gili Naveh, a research student in the group of Prof. Stephen Weiner of the Structural Biology Department. During long exposure to the X-rays inside the machinery, such delicate samples as biological specimens are generally submerged in liquid (usually ethanol or water), but such immersion significantly reduces the quality of the images. Naveh and Brumfeld developed a method of saturating the air surrounding the sample with vapor, thus preserving the specimens’ structure while leaving a clear path for the X-rays to penetrate.

The microtomography instrument in Brumfeld’s lab has been used by Institute scientists to reveal, among other things, the internal structure of developing bone, the microstructure of the soft tissue inside teeth, soil infiltration, tiny defects in diamonds, particles of minerals and silica in plant tissue, the shape of micromachinery tools and more.

 
 
 
 
 

 

 
 Hula painted frog. Image: Frank Glaw
Chemistry
English

When Material Worlds Unite

English

 

Profs. David Cahen, Leeor Kronik and Ron Naaman

 
 
 
An emerging class of materials and devices – organic electronics – has attracted much attention in the past two decades.  In this world, such traditional inorganic semiconductors as silicon are combined with organic (carbon-based) materials. In combining desirable properties from both worlds – a nearly infinite choice of possible combinations – organic-inorganic materials offer a number of advantages over conventional inorganic semiconductors. Many can be produced at low cost; they can be light and easy to produce; and they can be designed with mechanical and chemical flexibility in mind.

In fact, such materials as organic light-emitting diodes (OLEDs) are already in use today in digital displays for TV screens, computer monitors and smartphones.
 
Often overlooked when combining two materials is the interface – the area in which they meet. That thin boundary turns out to be crucial for the properties of new materials, especially for those used in electronic devices. “The interface is so important, it is essentially what makes or breaks our ability to use an electronic material,” says Prof. David Cahen of the Materials and Interfaces Department.

At the Weizmann Institute, various groups are conducting cutting-edge research into organic-inorganic interfaces from all angles – from theory to experiments. This has led to highly fruitful collaborations both within Weizmann and beyond; an Israel Science Foundation grant, awarded to them together with scientists from Bar-Ilan and Tel Aviv universities, designates this research a scientific “Center of Excellence.”  
 
inorganic-organic interface
 
 
 

Guided intuition


Prof. Leeor Kronik, Head of the Institute’s Materials and Interfaces Department, focuses his research on the theoretical: the novel electronic, optical and magnetic properties of organic-inorganic interfaces. His main tools are so-called first principles calculations – calculations based on the laws of quantum physics, in which a material’s properties are predicted from nothing more than the type of atoms of which it is made up.

“Although we have well-developed models for both organic and inorganic materials,” says Kronik, “combining these two different worlds creates a truly new class of materials, bringing with it novel, unexpected phenomena.” One striking example is the observation of magnetism at the interface between two non-magnetic materials – a discovery of Prof. Ron Naaman of the Chemical Physics Department. “Building new theories on traditional models can be misleading; but a bottom-up approach, using first principles calculations, can guide us to understanding such unique phenomena,” says Kronik.

To predict the electronic structure and properties of atoms and molecules making up a material, scientists use density functional theory (DFT), currently the only practical way of conducting first principles calculations of systems with many thousands of electrons. DFT calculations are exact – in principle – but their practical application is always approximate. So Kronik and his group are developing new theoretical methods and equations to refine DFT, in hopes of gaining a more accurate understanding of these new materials.
 

Control, control, control

Much of materials research revolves around the control of structure, since it is a material’s molecular structure that ultimately determines its properties. The idea of using organic materials at interfaces is attractive precisely because it is easier to manipulate their structure and composition than those of inorganic materials.

 
An electron-transmission microscope (TEM) image of a methyl-styrene monolayer (“white stripe”) about 1 nm thick at the interface between silicon (Si) and lead (Pb). The superimposed schemes of molecules are in scale with the molecular monolayer
 
Prof. David Cahen, who helped pioneer the  field together with Prof. Abraham Shanzer of the Institute’s Organic Chemistry Department, is finding ways to optimize conventional electronic materials by adding organic materials at their surface, specifically to the silicon in solar cells.
 
The use of silicon – the ubiquitous semiconductor material found in most electronic devices today – became possible only once industry figured out a way to “tame” its “messiness” through the process of oxidation: A thin oxide layer is grown on its surface. This offers a controlled decrease in defects at the interface between the silicon and the oxide, as well as adding a protective layer to the silicon. But oxidation is a difficult process; placing a thin layer – one to three atoms thick – of organic molecules at the interface leads to better control and opens up the potential for obtaining new properties.
 
Why is this important for solar cells? The best conventional solar cells are close to their theoretical limit (about 30%), but most are much less efficient; much of the avoidable energy loss is the result of less-than-optimal control at the interface. “Though solar cells made with organic materials are not yet in commercial use, the example of organic LEDs, which are already being manufactured and used, gives us hope that it’s only a matter of time before organic photovoltaics will mature into a viable technology,” says Cahen. “Along the way, we are learning the fascinating science of these interfaces.”

 

Putting a spin on it

Experimental system for measuring spin specific electron transfer through DNA
 
In another area of organic electronics known simply as molecular electronics, single molecules or one-molecule-thick layers of an organic compound are the active elements of electronic devices. This branch is being explored by Prof. Ron Naaman. More specifically, his research focuses on spin electronics or “spintronics.” Spintronic devices take advantage of an electron’s spin – a quantum property – and Naaman is trying to figure out, among other things, how spin can be used for memory devices and computing. Such computers would harness the power of atoms and molecules to perform calculations significantly faster than any silicon-based computer. Although they are mostly a “sci-fi” notion at present, Naaman is making some interesting strides toward turning this notion into reality.

An electron’s spin has two possible states, either “up” or “down,” and changing the ratio of spins in a material can change its properties. Controlling electron spin within a device is usually achieved with magnetic layers; but the use of these is complex, and they are sensitive to heat and cold.

Naaman discovered that spin direction can be controlled with organic, biological molecules, especially helical, double-stranded DNA. He based this discovery on a well-known property of organic molecules: They exist in either “left-” or “right-handed” forms that cannot be superimposed on one another. When Naaman exposed DNA to mixed groups containing electrons with both directions of spin, the DNA “preferred” electrons with one particular spin over the other.

Naaman: “DNA has turned out to be a superb ‘spin filter,’ and this concept has opened up new avenues in using organic materials for spintronics.”
 

 

Joining forces
 

“The overwhelming response we received from students and postdocs around the world is testament: This field is alive and well,” says Prof. Leeor Kronik, co-organizer of the 7th International Conference on Electronic Structure and Processes at Molecular-Based Interfaces (ESPMI VII), recently hosted at the Weizmann Institute of Science. The conference brought together some of the best minds in the field, providing a platform for sharing the latest research results as well as the opportunity to consolidate old collaborations and forge new ones. To make the conference more useful to those at the beginning of their career, mainly students, a workshop with tutorials was organized by Weizmann Institute students in the days before the actual meeting.
 
The conference was attended by more than 150 scientists; some 42 acknowledged experts in the field – from the USA, through Europe, to Japan – were invited to speak. Kronik: “The decision to hold the conference in Israel this year is recognition that important and interesting research on organic-inorganic interfaces is being conducted here.”
 
Interfaces conference
 
 

 

 
Prof. David Cahen's research is suppored by the Mary and Tom Beck Canadian Center for Alternative Energy Research,  which he heads; the Leona M. and Harry B. Helmsley Charitable Trust; the Nancy and Stephen Grand Center for Sensors and Security; the Ben B. and Joyce E. Eisenberg Foundation Endowment Fund; the Monroe and Marjorie Burk Fund for Alternative Energy Studies; the Carolito Stiftung; the Wolfson Family Charitable Trust; the Charles and David Wolfson Charitable Trust; the estate of Theodore E. Rifkin; and Martin Kushner Schnur, Mexico. Prof. Cahen is the incumbent of the Rowland and Sylvia Schaefer Professorial Chair in Energy Research.   

Prof.  Leeor Kronik's research is supported by the Wolfson Family Charitable Trust; the Carolito Stiftung; the European Research Council; the Leona M. and Harry B. Helmsley Charitable Trust; and Antonio and Noga Villalon, Winnetka, IL.
 
Prof. Ron Naaman's research is supported by the Nancy and Stephen Grand Research Center for Sensors and Security, which he heads; and the estate of Theodore Rifkin. Prof. Naaman is the incumbent of the Aryeh and Mintzi Katzman Professorial Chair.
 
Prof. Abraham Shanzer is the incumbent of the Siegfried and Irma Ullmann Professorial Chair.

 
ontrol, control, control
Profs. David Cahen, Leeor Kronik and Ron Naaman
Chemistry
English
Yes

Cancer at a Breaking Point

English
 
 
Drs. Yotam Drier (left) and Gad Getz at the Broad Institute

 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Like police detectives using DNA fingerprinting in their effort to eradicate crime, cancer researchers are building a DNA profile of malignancy in an attempt to eradicate cancer. One of their greatest challenges is that they are not dealing with a single criminal: There are at least 200 forms of cancer, and many more subtypes. The goal is to “fingerprint” each one of these subtypes so that, ultimately, people with cancer can be treated with genetically matched personalized therapies.

Important strides in bringing this vision to reality have emerged recently from a collaboration between the Weizmann Institute of Science, on the one hand, and the Eli and Edythe L. Broad Institute of Harvard University and the Massachusetts Institute of Technology, on the other. Both sides of this collaboration are linked to the laboratory of Prof. Eytan Domany in Weizmann’s Physics of Complex Systems Department: Some three years ago, Domany’s former Ph.D. student Dr. Gad Getz, today Director of Cancer Genome Computational Analysis at the Broad Institute, joined forces with Dr. Yotam Drier, then Domany’s student, at Weizmann.
 
 
A cancer genome is the full set of DNA in the tumor’s cells, each tumor type being characterized by its own genomic abnormalities. Getz’s team at the Broad Institute – numbering some 30 biologists, biochemists, physicists and software engineers – is participating in the Cancer Genome Atlas, a collaborative effort led by the U.S. National Institutes of Health, as well as in other studies aimed at the same goal: deciphering the genomes of all major tumor types.

These ambitious projects have been made possible by the relatively recent advent of high-throughput sequencing, in which numerous DNA segments are “read out” in parallel. By dramatically speeding up the sequencing process, this technology has led to an equally dramatic drop in costs: from $30,000 per million DNA bases in 1999 to a mere 10 cents in 2011. As a result, scientists can now rapidly sequence hundreds of whole tumor genomes, each genome comprising billions of DNA base pairs. But the sequencing alone is not enough: making sense of these mounds of genomic data is no less of a challenge.
 
DNA structural rearrangements and copy number alterations detected in a colorectal tumors displayed as a CIRCOS plot. Source: Nature Genetics
 
Getz’s group at Broad is developing computational tools for analyzing such data. When Getz, on a visit to the Weizmann Institute in December 2008, asked his former thesis adviser Domany if someone in his team would be interested in taking part in this work, Domany suggested Yotam Drier. Getz and Drier's similar backgrounds promised a fruitful collaboration: Both had done their army service through the prestigious Talpiot program, during which each obtained a university degree in math and other exact sciences, Getz majoring in physics, Drier in computer science.

Indeed, Drier soon developed BreakPointer, a computer algorithm that scans the whole human genome for a hallmark of cancer: faulty DNA repair resulting in structural rearrangements that differ from the normal DNA sequence. It was the first algorithm to detect the exact break points in DNA at which such rearrangements occur. “This tool is now a major part of our effort to map out all the genes and other phenomena that contribute to cancer,” says Getz.
 
 
Incorporated into all cancer genome analyses at the Broad Institute, BreakPointer has since helped scientists make a number of significant discoveries, including the uncovering of the crucial cancer-related defects after which the algorithm was named: DNA rearrangement break points.  As reported in Nature, BreakPointer has helped reveal a previously unknown pattern of chromosomal rearrangements in prostate cancer: complex chains of rearrangements that occur within or adjacent to known cancer genes. Moreover, the scientists discovered a relationship between the location of break points and the condition of chromatin, a major component in the protective packaging of chromosomes, suggesting that genomic rearrangements may be related not only to genes but to epigenetic factors – that is, factors not directly encoded in the genome. 
 
In a study of colorectal cancer reported in Nature Genetics, the scientists used BreakPointer to discover 11 DNA rearrangements leading to abnormally fused genes. Among these was the first “recurrent” gene – so called because it recurs in different tumors – to be described in colorectal cancer.  Abnormally fused genes produce abnormal proteins, which may serve as potential drug targets – not only because they are required for the cancer to thrive, but also because these proteins don’t exist in healthy cells – which means that the drug can be specifically directed at the tumor cells, sparing healthy tissues.
Prof. Eytan Domany
 
"BreakPointer identifies the precise location of break points in the cancer genome by looking for 'suspicious' sequences and comparing them to relevant areas in a reference genome,” says Drier, who now conducts postdoctoral research at Harvard Medical School and the Broad Institute. “When we applied the algorithm, we found correlations between DNA rearrangements and other features of the genome, such as point mutations and the condition of the chromatin.” Such correlations and their biological significance in different cancers are to be described in an upcoming issue of Genome Research.

The mapping of all the major cancer genomes will enable researchers to better understand the molecular processes that drive cancer, facilitating the search for drugs tailored to each tumor’s unique genetic defects. Such targeted therapies already exist for a limited number of cancers, and their number is constantly growing. One day in the future, doctors will be routinely mapping the genome of the cancer of each individual patient and prescribing genetically tailored drugs, maximizing the effectiveness of treatment and minimizing its side effects.  
 
Prof. Eytan Domany's research is supported by the Kahn Family Research Center for Systems Biology of the Human Cell, which he heads; the Leir Charitable Foundations; and Mordechai Segal, Israel. Prof. Domany is the incumbent of the Henry J. Leir Professorial Chair.
 
 
 
 
Drs. Yotam Drier (left) and Gad Getz at the Broad Institute
Math & Computer Science
English

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