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Latest RESEARCH Latest RESEARCH

CHAOS RESEARCH BIOCHEMISTRY that there is an “anti-sense ma-


chine” in each cell, which possibly
Chemists Control the Hurricane Silencing Specific Genes wards off viruses and transposable
elements. A protein complex, which
Spontaneous structure for- carbon dioxide which immedi- Scientists from the Max Planck defects. The latter is particularly still remains largely unknown, evi-

PHOTOS: FRITZ-HABER-INSTITUTE OF THE MAX PLANCK SOCIETY


mation and complex chaos ately leaves the surface again. Institute for Biophysical Chem- interesting for therapeutic applica- dently checks all mRNA molecules
are some of nature’s most In certain conditions, the prod- istry, Göttingen, have developed tions. in the cell that it comes across.
fascinating phenomena. Now, uct flow is not constant and a relatively simple and universal How does the “RNA interference” mRNAs containing the same se-
for the very first time, scien- self-organized patterns form method of silencing individual method work? Genes are made up quence as the delivered RNA dou-
tists led by Prof. Gerhard Ertl on the surface. Ertl and his col- genes. This method has now been from a string of nucleotide build- ble strand are cleaved, while mR-
at the Fritz Haber Institute leagues therefore took a closer successfully tested for the very ing blocks (DNA). These chains of NAs with a different sequence re-
of the Max Planck Society, look at what goes on here. first time in human cell cultures. nucleotides are transcribed into main unchanged. Through the syn-
Berlin, have succeeded in not They are able to view the The concept of “RNA interfer- so-called messenger RNAs (mRNA) thesis of sequence-specific RNA

FIG.: MPI FOR BIOPHYSICAL CHEMISTRY


only observing, but also con- process using the special “pho- The results of ence” is simple and can be ap- which supply the cell with the double strands, researchers are able
trolling chaotic structures in toelectron emission micro- requires further opening or experiments on plied in principle to any RNA building instructions for the re- to determine which particular tar-
CO oxidation (left)
a chemical reaction. They scope” also developed by the closure. This takes place with a sequence. It represents an ideal spective proteins. If so-called siRNA get mRNA is to be destroyed.
and its mathe-
have managed to transform a Fritz Haber Institute. What is specific time delay that can be tool for functional genome molecules are locked into the cell, The siRNA-based knockdown pro-
matical modelling
chaotic system into an or- noticeable is that the spatial varied along with the intensity (right). Space-time analysis and could open up this leads to the destruction of the cedure is much more reliable than
dered one (SCIENCE, 18 May covering patterns are accom- of the feedback signal. diagrams are given new therapeutic perspectives target mRNA. This is broken up conventional anti-sense methods
2001). Scientists had previ- panied by temporal fluctua- Under these experimental con- for two different in the long term. (NATURE, into small fragments, thereby los- because standard anti-sense tech-
ously predicted the new tions (oscillations) within a cy- ditions, the new patterns were patterns in each 24 May 2001). ing its ability to provide the build-
structures through mathe- cle of only a few seconds. The able to develop in a self-orga- case along a cut ing instructions for a specific
matical modelling. oxygen and carbon monoxide nized manner. The Max Planck surface – above Ever since the discovery of genes, protein. The new method does
fronts appear in different researchers have thereby pro- chaotic ring struc- scientists have been interested in not eliminate the gene but only its
When the smallest of changes colours in the video image. We vided evidence that high-di- tures, below isolating individual genes in order functional product – the messen-
regular domains.
in the initial state have enor- can see that they form spiral- mension chaos can be con- to understand how they function ger RNA is “intercepted”, so to
mous consequences on the shaped turbulence, similar to a trolled using simple methods. or to prevent the development speak. The construction of the ap-
product, scientists talk of hurricane. The scientists con- “The principles that we con- of genetic defects and diseases. propriate siRNA molecules is so
chaos. This includes the cli- verted this hurricane into an ceived for this simple system However, it often took years of specific that, in each case, they de-
mate, the creation of turbu- ordered pattern of coverage. can be applied to other prob- hard work to silence just one single stroy only the messengers of a sin-
lence in liquid flows, and the Using mathematical model lems,” says Gerhard Ertl. The gene. The new procedure now gle gene. “RNA interference is simi-
aggregation of bacteria in calculations, theorists working scientists are now working on seems capable of achieving this lar in principle to the anti-sense
biological systems. However, with Alexander Mikhailov have the development of more com- within a much shorter time scale method”, says Thomas Tuschl. “An
chemical reactions can also predicted that it is possible to plex feedback systems which and is suitable for all types of RNA sequence complementary to
take place in a chaotic manner. suppress the chaotic structures would enable them to synchro- genes. Thomas Tuschl devised the the messenger RNA is also used
Scientists at the Fritz Haber using a feedback loop. New nize systems consisting of more procedure at the Massachusetts here. However, we add in the anti- In order to demonstrate the silencing of a specific
Institute chose the catalytic patterns, previously hidden in than two partners. “In this way Institute of Technology in Boston sense RNA in the form of a double- gene expressed in a human cell, an RNA double strand
conversion of carbon monoxide the chaos, would thereby it may be possible for the yield (USA) and put it into practice last stranded RNA.” was directed against a segment selected from the cod-
Various patterns into carbon dioxide for their emerge. Harm Hinrich Roter- of a desired product to be en- year together with Sayda Elbashir A decisive factor in this scientific ing sequence of the lamin A/C gene which encodes a
in the oxidation component of the inner cell membrane (a). The effect
investigations. The reaction mund is the scientist in charge hanced, and the formation of in his working group at the Max breakthrough was the discovery
reaction of carbon is demonstrated by means of immunofluorescence
monoxide on a
takes place on a platinum (110) of these experiments. He and unwanted byproducts to be Planck Institute for Biophysical that trapped nucleotide chains
microscopy: in most cases, the corresponding protein
platinum surface, single crystal catalyst and is a his group have gradually creat- suppressed during a chemical Chemistry, Göttingen. In collabora- must consist of 21 nucleotide
did not continue to form. In a control experiment,
captured using type of model reaction. The ed chequered patterns, stripes, reaction,” explains Ertl. ● tion with Jens Harborth and Klaus building blocks. RNA molecules of whereby one RNA double strand was used against
special microscopic atoms formed from gaseous and uniformly oscillating Weber, both scientists succeeded in this length can recruit proteins in one sequence which does not exist in a human cell,
technology. The oxygen molecules are securely waves. They were able to silencing specific individual genes the cell that have so far remained no effect can be observed (b). In the lower sequence
blue areas are cov- attached to the surface of the achieve this by feeding the @ Further information in human cells. This procedure unknown. These proteins then form (c+d), the influence of both RNA double strands was
ered mainly with platinum and wait here for information coming from the can be obtained from: therefore offers a new and highly a complex which carries out the investigated in each case on a different gene with
oxygen and the DR. HARM HINRICH ROTERMUND
their reaction partner – a car- microscope back to the reac- specific method of examining the recognition and cleavage of the a different sequence. In this particular case, no reduc-
red areas with Fritz Haber Institute of the
bon monoxide molecule. This tion vessel. A computer re- functioning of human genes. This cognate mRNA molecule. Observa- tion was observed. The effect is therefore specific.
carbon monoxide. Max Planck Society, Berlin
moves freely and jumps, so to ceives the current and continu- tel.: +49-30/8413-5129 is of particular interest as the se- tions in the fruit fly Drosophila
Left to right:
chaotic spiral
speak, across the surface. When ously carries out new calcula- fax: +49-30/8413-5106 quence of most genes encoded in melanogaster have further assisted nology normally requires the test-
waves and ring it finds an oxygen atom, the tions to determine whether or e-mail: the human genome have now been the scientists in this area: when ing of thousands of anti-sense se-
structures created two can join together to form not the carbon monoxide valve rotermun@fhi-berlin.mpg.de identified. Yet, their function still extremely long double-stranded quences in order to find one that
artificially by remains largely unknown. Using RNA sequences were introduced specifically blocks the expression
means of feed- this new method, it will now be into the cells, these were split by of a given gene. In contrast, almost
back, regular possible to carry out the specific an enzyme into double-stranded any siRNA cognate to the targeted
domains, and and selective isolation of different RNA with a length of predomi- gene is believed to work. The re-
stripe patterns. RNA variants, which make up the nantly 21 nucleotides. The individ- searchers therefore regard this
complexity of the human genome. ual stages of the silencing process as a breakthrough for functional
In the long-term, it may also be in the cell are still not understood. genome analysis. To find out about
possible to eliminate gene-specific However, the scientists suspect the functions of the 30,000 or

12 M A X P L A N C K R E S E A R C H 4 / 2 0 0 1 4/2001 M A X P L A N C K R E S E A R C H 13

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