The new technique provides a detailed look into processes that until now were proven but never visualized. The more detailed view of DNA being made into RNA in a single cell will help answer questions about how much of a gene is made over time and how much that level varies from cell to cell. Insight into how genes work at a more precise level, ultimately advances understanding of disease mechanisms that trigger cancer, for example, which arise when genes no longer work at their correct capacity or time.
“The classic textbook cartoon illustration of a single strand of DNA with little mRNA pieces coming off it can now be shown with real photographs,” explained Daniel Zenklusen, Ph.D., an Einstein post-doctoral fellow and first author of the study. The technique was developed in the laboratory of Robert Singer, Ph.D., co-chair and professor of anatomy and structural biology at Einstein.
The new technology is a powerful refinement of fluorescent in-situ hybridization (FISH), developed in Dr. Singer’s laboratory more than 26 years ago. FISH is now a widely used research tool to study gene activation; that is how much a gene has been “turned on” in groups of cells. FISH is also used in genetic counseling to detect the presence of gene features that diagnose conditions including Down’s syndrome or Prader-Willi syndrome.
Advances in fluorescence, microscopy and data analysis enabled the more powerful FISH application described in the paper. Until this work, FISH could only be used to look at genes or their messages that are present at very high levels and only in tissues, not at the smaller level of the cell. However, this it the first time that all the individual mRNA molecules within single cells can be counted.
Dr. Singer’s “single RNA counting” technique has the potential to change some fundamental theories about how genes are regulated. As Dr. Singer explained, “our study using this new technique has already generated enough new ideas to keep students busy for the next 10 years.”
One of the most important findings of this study was that “housekeeping” genes, which all cells need to survive, are not always expressed at a constant level. Variability, however, is restricted to a narrow range that seems to be characteristic for housekeeping genes. Combining single molecule measurement with mathematical modeling allowed the team to precisely determine how variability is controlled. This showed that unlike the findings of previous studies, housekeeping genes are not transcribed by transcriptional bursts but at a fairly constant rate. Bursting expression, however, is found for special classes for genes where higher variability might be an advantage for the cell. The next step is to see if this continuous/non-bursting theory of housekeeping gene control applies also to human cells. The work from Dr. Singer’s group was performed in yeast cells.
Dr. Singer believes the approach of looking at biological processes in natural contexts (rather than in a test tube) at a single cell level reveals details that can advance the field of cancer and other disease research. “Cancer derives from a single cell. So current microarray technologies that are used on a tissue-wide level and are based on “grinding up a tumor” may be a good first step at directing us where to focus, but they may need to be combined with newer techniques that provide the precision to home in on single cells,” Dr. Singer said.The study, “Single-RNA Counting Reveals Alternative Modes of Gene Expression in Yeast,” by Daniel Zenklusen, Daniel R. Larson and Robert H. Singer appears in the November 16, 2008 online edition of Nature Structural and Molecular Biology.
http://www.nature.com/nsmb/journal/vaop/ncurrent/index.htmlAbout Albert Einstein College of Medicine of Yeshiva University
Michael Heller | Newswise Science News
Research team creates new possibilities for medicine and materials sciences
22.01.2018 | Humboldt-Universität zu Berlin
Saarland University bioinformaticians compute gene sequences inherited from each parent
22.01.2018 | Universität des Saarlandes
On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.
We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...
What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...
For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.
Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...
At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.
No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...
Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.
Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...
08.01.2018 | Event News
11.12.2017 | Event News
08.12.2017 | Event News
22.01.2018 | Materials Sciences
22.01.2018 | Earth Sciences
22.01.2018 | Life Sciences