Einstein researchers develop technique to count messages made by single genes

December 02, 2008

November 16, 2008 - In a study in the advance online edition of Nature Structural and Molecular Biology, researchers from Albert Einstein College of Medicine describe a technique for looking more precisely at a fundamental step of a cell's life - a gene, DNA, being read into a message, mRNA. The technique could provide a window into the process by which genes are switched on inappropriately, causing disease.

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.
-end-
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.html

To request a single reprint from the authors, contact:

Michael Heller
Manager Media Relations, Albert Einstein College of Medicine
Mheller@aecom.yu.edu
(718) 430-4186

About Albert Einstein College of Medicine of Yeshiva University
Albert Einstein College of Medicine of Yeshiva University is one of the nation's premier centers for research, medical education and clinical investigation. It is the home to some 2,000 faculty members, 750 M.D. students, 350 Ph.D. students (including 125 in combined M.D./Ph.D. programs) and 380 postdoctoral investigators. Last year, Einstein received more than $130 million in support from the NIH. This includes the funding of major research centers at Einstein in diabetes, cancer, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Through its extensive affiliation network involving five hospital centers in the Bronx, Manhattan and Long Island - which includes Montefiore Medical Center, Einstein's officially designated University Hospital - the College runs one of the largest post-graduate medical training program in the United States, offering approximately 150 residency programs to more than 2,500 physicians in training. For more information, please visit www.aecom.yu.edu.

Albert Einstein College of Medicine

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.