Life's Twists and Turns

English
 
Prof. Joel Stavans. "Technology has brought biology closer to physicists"
 

 

 

 

 

 

 

 

 

The Tower of Babel. That's what you often find when you put biologists and physicists together. Biologists, possessing a rich vocabulary of molecular nomenclature and conditions, are regarded by physicists with bewilderment. And the physicist's minimalistic terminology, which strives to describe the universe and everything in it in terms of a few forces and particles, seems to biologists incomprehensibly sparse.
 
But communicative sparks between the two groups can, at times, be observed. Take Prof. Joel Stavans, a physicist, and Dr. Opher Gileadi, a biologist. They are working side by side to decipher a language that is equally enigmatic to both: the DNA molecule's secret code of life.
 
Unlike biologists who have focused mainly on identifying the genes lodged in the DNA, Stavans of the Physics of Complex Systems Department and Gileadi of the Molecular Genetics Department peer at DNA from a different angle. What happens when you stretch a DNA molecule, when does the DNA fold, and what effect does this have on gene expression?
Biologists have found that a molecule in our body that is a motor, scanner and printer all in one, plays an important role in gene expression. Called RNA polymerase, this multitalented molecule seats itself on one end of a gene. It then travels along the gene, producing a "print-out" of the genetic sequence. This printout is in fact a molecule called RNA. It is carried from the DNA to a "protein factory" which, reading the printout, manufactures the proper protein.
 
But what is it that determines on which gene the machine will seat itself, i.e., what determines which gene will be expressed at a particular time? DNA contains certain sections that are "instruction manuals": they specify when and where RNA polymerase should start its work. These sections (called regulatory sequences) are placed in between the genes, which themselves constitute only a small portion of the DNA.
 
At times, an instruction manual can be positioned at a great distance from the gene that it wants to activate. To cause the gene's activation, it must get closer to the gene. Biologists have found that this often occurs by the looping of intervening DNA (much like the "loop" that is formed when bringing our forehead to our otherwise faraway knees). Naturally, the forces and factors that can influence DNA looping are of critical importance for the function of genes.
 
In the loop
"To study looping, we are looking for ways to induce the DNA to loop," says Stavans. One known method is to introduce a special protein into the DNA's environment. It is a DNA-binding protein, meaning that it binds to the DNA at certain sites. Stavans and Gileadi inserted into the DNA two sites for which the protein has an affinity. The protein, spotting two sites that it "liked," simultaneously attached itself to both sites and brought them together in a loop.
 
Though scientists cannot see the looping itself since it is much too small, they have developed a method providing them with evidence of looping. One end of the DNA strand is attached to a surface and the other to a bead large enough to be detected using a microscope. When a loop is formed, a decrease in the distance between the bead and the surface can be observed. Stavans and Gileadi are using this method to understand the physical rules that govern looping and the factors that affect it in living cells.
 
Says Stavans: "Technology has brought biology closer to physicists. Now it is possible to analyze one strand of DNA, a concept attractive to a physicist, who usually strives to reduce complex systems to their simple components."
 
Life Sciences
English
  • DNA
  • Joel Stavans
  • Molecular Genetics
  • Physics of Complex Systems

Lost in Cyberspace? Take GeneCards

English

Yaar, Chalifa-Caspi and Safran. Intelligent interface

Even the most experienced cyberscientist can easily get lost in the vast labyrinth of data on human genes available on the Internet thanks to the international Human Genome Project. Now Weizmann Institute scientists have created GeneCards, a new on-line database and software tool that provides scientists, biotechnologists, physicians and teachers with fast and convenient access to the genetic information they need.

GeneCards is updated on an ongoing basis by software "robots" ­ intelligent computer programs that search relevant genomic databases and websites, then organize and present the data in a concise and easy-to-read format. This automatic procedure, known as data mining, guarantees that when you access GeneCards, you're always looking at the most up-to-date information.

GeneCards was created by a team that included postdoctoral fellows Drs. Michael Rebhan and Vered Chalifa-Caspi and doctoral student Gustavo Glusman. The team is headed by Prof. Doron Lancet of the Molecular Genetics Department, head of the Institute's Genome Center, and Dr. Jaime Prilusky of the Biological Services, head of Weizmann's Bioinformatics Unit. Currently, it also includes postdoctoral fellow Dr. Liora Yaar and engineer Marilyn Safran.

GeneCards features a page, or card, for every human gene. Each card contains a particular gene's vital statistics, such as its official name, the protein it encodes, its functions in the cell, its location on a chromosome, and information about the diseases caused by its mutations. It may also list similar genes found in organisms other than humans or provide links to other relevant sites based on bioinformatics, the dynamic new discipline that combines biology with computer science.

One of GeneCards' most striking features is its "intelligent interface" which helps searchers reach more efficiently the data they need. For instance, if a query produces no results, the database may suggest a way to reformulate the question, correct a spelling error, or provide tips on where else to look for information.

Currently, GeneCards contains information on over 7,000 human genes that have already been clearly identified and named by scientists deciphering the human genome. It is now being augmented to include tens of thousands of new genes that have been identified, but whose function is not yet known. By the time the Human Genome Project is completed (probably around the year 2002), the database will encompass all 80,000-100,000 human genes.

By fall 1998, the GeneCards site averaged about 22,000 hits per month from around the globe. It's generated special interest among Israeli and foreign biotechnology firms interested in developing new drugs based on human gene information.

Visit the GeneCards website at: http://www.genecards.org/
Life Sciences
English
  • Data bank
  • Doron Lancet
  • Gene
  • Molecular Genetics

Centers of Excellence: Gene Targeting

English

The Israel Science Foundation has recently initiated the establishment of Centers of Excellence at the country's leading academic institutions. The goal of this program -- to provide recognition and support for the work of outstanding groups of local scientists engaged in research at the highest international level. Ten Centers have been created to date, six of them headed by Weizmann Institute professors. Interface describes the activities of three Weizmann-led Centers of Excellence.

Prof. Peter Lonai. Major implications for medical research

How does a complex, three dimensional embryo develop from a single cell without major mistakes occurring in the process? What causes tissues to grow uncontrollably in certain types of cancer? These are the kinds of questions tackled by the Center of Excellence for the study of genes headed by Prof. Peter Lonai

The Center takes advantage of the Weizmann Institute's expertise in the technique known as gene targeting, in which specific defects are introduced into genes in order to clarify their function. The method has been hailed as one of the most important advances in molecular genetics and is expected to have major implications for medical research.

Lonai, who played a leading role in introducing gene targeting to Israel, uses the technique to clarify embryonic development. The commonly held theory is that this process is entirely predetermined by a genetic code or DNA program. Lonai disagrees.

"A living organism does not take shape like a fighter plane, in which the instructions for every single component are programmed in advance. In living organisms, messages are constantly being sent back and forth between cells, with each cell helping to define what will happen to the others," says Lonai.

"We know a lot about embryonic development in flies and worms, but very little about how this process occurs in mammals. In fact, we don't usually give much thought to this crucial stage of life. It is only when we notice a mutation, like a little finger twice as long as it should be, that we start to appreciate how amazing it is that the body's countless components usually come out just right."

Gene targeting makes it possible to perform sophisticated studies in mammals that until now were possible only with much simpler organisms. "It will soon become the primary method for analyzing cloned genes," says Lonai.

Since breakdowns in intracellular signals controlling the growth of tissues are known to cause certain types of malignancies, this study also is expected markedly to advance cancer research.

The new Center of Excellence, which provides expertise in gene targeting to scientists throughout the country, includes four research groups -- three led by Weizmann Institute scientists and one by a Bar-Ilan University researcher. In addition to heading the new Center, Lonai, a member of the Immunology Department, is in charge of the three Institute teams. The other two are led by Profs. David Givol and Yosef Yarden of the Molecular Cell Biology Department.
 
 
Life Sciences
English
  • David Givol
  • Gene
  • Immunology
  • Molecular Cell Biology
  • Yosef Yarden›Yosef Yarden

Greater Role for Weizmann Institute in Human Genome Project

English

 

Pilusky and Esterman. big in bioinformatics
 

The Weizmann Institute is slated to play an increasingly important role in the Human Genome Project, which is expected to provide researchers with a molecular "encyclopedia" of human genes and yield new possibilities for diagnosing, preventing and treating numerous disorders.


This enhanced participation, which will significantly upgrade Israel's genetic research infrastructure, was made possible by major grants received by the Weizmann Institute and Tel Aviv University from Israel's council for Higher Education, on the recommendation of the Israel Academy of Sciences and Humanities. The funds will aid the establishment of the Israel National Genome Project, which will encompass a Bioinformatics Genome Resource Core (BIGROC) at the Weizmann Institute and a National Laboratory for Israel Population Genetics at Tel Aviv University.

These facilities will enable local scientists to become full partners in the Human Genome Project, the 15-year $3-billion undertaking that was launched by the world scientific community in 1989 on the initiative of the U.S. government. At the Weizmann Institute, the Council for Higher Education grant, together with a parallel major grant provided by the Israel Ministry of Science and the Arts, will help improve the country's bioinformatics infrastructure. This includes the computers and on-line connections operated by the Institute's Biological Computing Division, which provide scientists with access to daily updated, international biology databases and the ability to interact with researchers abroad. In addition, the Institute's Biological Services Unit, which already has three automated DNA sequencing machines and other necessary ancillary equipment, will be further expanded to better serve the country's genetic researchers and dozens of investigations going on at the Institute itself. New DNA sequencing technologies are currently being implemented.

The Weizmann contingent of the Genome Resource Core will also receive support from UNESCO in order to assist other countries in setting up their own biological information banks. Such bioinformatics collaboration with Poland is already under way.

The Bioinformatics and Genome operations at the Weizmann Institute of Science are supervised by a committee headed by Prof. Doron Lancet of the Department of Membrane Research and Biophysics and includes Prof. Marvin Edelman of the Department of Plant Genetics, Dr. Levy Ulanovsky of the Department of Structural Biology and Prof. David Givol, Department of Chemical Immunology. Operations are carried out by Prof. Menachem Rubinstein, Head of Biological Services; Mr. Leon Esterman, an engineer who heads the Biological Computing Division; and Dr. Jaime Prilusky, Head of the Bioinformatics Unit.

Prof. Edelman holds the Sir Siegmund Warburg Chair of Agricultural Molecular Biology; Prof. Givol, the Oscar H. And Anne Altshuler Chair of Immunochemistry; and Prof. Rubinstein, the Maurice and Edna Weiss Chair of Interferon Research.
 
 
Life Sciences
English
  • Bioinformatics
  • David Givol
  • Doron Lancet
  • Gene code
  • Human Genome Project
  • Marvin Edelman
  • Menachem Rubinstein

Joining the Race to Decipher the Human Genome

English

Mehlman, Rubinstein and in new DNA lab

Israeli molecular biologists can now participate fully in the international quest to decipher the human genome, thanks to a $500,000 automated DNA Analysis Laboratory that opened last year at the Institute. The Human Genome Project, a 15-year multinational endeavor to sequence man's entire genetic storehouse, will make it possible to pinpoint the genetic origins of all five thousand human genetic diseases, hopefully leading to improved understanding of the function and formation of complex organs, including the brain.

Within the first six months of Laboratory operation, nearly all Institute molecular biologists had abandoned their own non-automated genetic sequencing procedures and started submitting samples to the new facility, which is part of the Institute's Biological Services Unit. Its expertise is also available to the wider Israeli scientific community.

According to Prof. Menachem Rubinstein of the Department of Molecular Genetics and Virology and Head of the Institute's Biological Services Unit, benefits have already been realized in Institute projects bearing on Down syndrome, human reproduction, the basis of odor detection, nerve repair and function, natural cancer protective mechanisms, and autoimmune diseases, among others.

DNA, the coded plan used by all living organisms to construct their various proteins, is a long chain-like molecule built from four different nucleotide bases tied together like a string of beads. The kingpin of the new Laboratory is a state-of-the-art DNA sequence analyzer, which accepts a gel loaded with as many as 36 different samples of specially prepared DNA and supplies a complete base sequence analysis in as little as eight hours.

Three other vital Laboratory components are soon to be added. One is a robot for liquid handling that will be able to automatically work up the DNA sample for insertion into the analyzer. The second component is a dedicated work station that will accumulate all data generated by the sequencer, reconstruct DNA chains too long to be handled by a single DNA analysis, and provide improved comparisons to known DNA sequences. The third instrument is a DNA fragment analyzer, which enables detection of genetic defects by separating, identifying and comparing large genetic segments.

Establishment of the automated sequencer facility was initiated by the Institute's Human Genome Committee, which supervises the Laboratory's integration into DNA-sequencing activities elsewhere. Its members are Profs. David Givol, Yoram Groner, Doron Lancet and Menachem Rubinstein. Equipping the Laboratory was made possible by a contribution from the Forchheimer Foundation and grants from the Planning and Budgeting Committee of the Israel Council for Higher Education and the Wolfson Family Charitable Trust.
 
Gene readout
 
 
 
Life Sciences
English
  • DNA
  • David Givol
  • Doron Lancet
  • Human Genome Project
  • Menachem Rubinstein
  • Molecular Genetics
  • Yoram Groner

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