Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers create DNA ’nanocircles’ to probe the mystery of aging in human cells

20.11.2002


A new form of nanotechnology developed at Stanford University may lead to a better understanding of the life and death of human cells.



Writing in the Nov. 18 Proceedings of the National Academy of Sciences (PNAS), Stanford researchers described how newly created circles of synthetic DNA - called "nanocircles" - could help researchers learn more about the aging process in cells.

"In the long run, we have this dream of making laboratory cells live longer," said Eric Kool, a professor of chemistry at Stanford and co-author of the PNAS study. "We thought of this pie-in-the-sky idea several years ago, and we’ve been working toward it ever since."


All cells carry chromosomes - large molecules of double-stranded DNA that are capped off by single-strand sequences called telomeres. In their study, the research team successfully used synthetic nanocircles to lengthen telomeres in the test tube.

"The telomere is the time clock that tells a cell how long it can divide before it dies," Kool noted. "The consensus is that the length of the telomere helps determine how long a cell population will live, so if you can make telomeres longer, you could have some real biological effect on the lifespan of the cell. These results suggest the possibility that, one day, we may be able to make cells live longer by this approach."

Cellular death

Human telomeres consist of chemical clusters called "base pairs" that are strung together in a specific sequence known by the initials TTAGGG. This sequence is repeated several thousand times along the length of the telomere. But each time a cell divides during its normal lifecycle, its telomeres are shortened by about 100 base pairs until all cell division finally comes to a halt.

"Suddenly there’s a switch in the cell that says, ’It’s time to stop dividing,’" Kool explained. "It’s still not completely clear how that works, but it is clear that once telomeres reach the critically short length of 3,000 to 5,000 base pairs, they enter senescence and die."

In nature, a chromosome can be lengthened by the enzyme telomerase, which adds new TTAGGG sequences to the end of the telomere. But because telomerase is difficult to produce in the lab, Kool and his co-workers decided to create synthetic nanocircles that mimic the natural enzyme.

Each nanocircle consists of DNA base pairs arranged in a sequence that is complementary to the telomere. When placed in a test tube, the nanocircles automatically lengthen the telomeres by repeatedly adding new TTAGGG sequences.

"Nanocircles are so simple they’re amazing," Kool observed. "Each nanocircle acts like a template that says, ’Copy more of that sequence.’ In the test tube, we start with very short telomeres and end up with long ones that are easy to see under the microscope with fluorescent labeling. This suggests the possibility that one day we may be able to make cells live indefinitely and divide indefinitely, so they essentially become refreshed, as if they were younger."

Aging and cancer

Kool pointed out that most cells have a limited lifespan, which is part of the normal aging process.

"The link between organism aging and cell aging is less clear, but there very likely is a link," he noted. "On the other hand, it is pretty clear that telomere length governs how long an individual cell lives."

In some diseases, such as premature aging (progeria) and cirrhosis, patients have cells with unusually short telomeres, Kool said. Cancer is another disease closely associated with telomere size.

"In order for a cell to become cancerous, one of the things it has to do is switch on the telomerase gene which makes the telomeres longer," he said. "The body has decided that the best way to keep an organism alive is to keep telomerase turned off, because otherwise you can get mutations and cancer too easily."

Because researchers need to study cells that live a long time, many labs rely on tumor-derived cells, which continuously divide and therefore are immortal. Kool predicted that nanocircle technology could one day provide an alternative method that would allow researchers to use healthy cells in their experiments instead of cancerous ones.

"If you could study normal cells in a convenient way, it would be a major boon for biomedical research," he noted. "You could go to the store and buy liver cells, pancreatic cells and skin cells and have them live indefinitely - if you could find a way to refresh their telomeres every couple of weeks or so. That has been our dream for this project: to find a way to refresh telomeres but without permanently turning on telomerase, which may increase the likelihood of cancer."

Transplantation medicine
Kool thinks nanocircle technology may prove useful in transplantation science and organogenesis.

"Perhaps some day researchers could grow new livers, new pancreas cells, new skin for burn victims," he said. "Instead of waiting for new donors to die, we could grow normal tissue in the lab. Maybe we wouldn’t need stem cells; we wouldn’t need to get into the controversy of where stem cells come from, if you could just take normal cells and grow them."

Kool and his colleagues also have begun research into the structure of single-strand telomeres, which are strikingly different from double-stranded DNA found in the rest of the chromosome.


The lead author of the PNAS study is Ulf M. Lindstrom, a former postdoctoral fellow in the Stanford Department of Chemistry now at Lund University in Sweden. Other Stanford co-authors are former Stanford undergraduate Ravi A. Chandrasekaran, now at the University of California-Berkeley; Stanford graduate students Lucian Orbai, Sandra A. Helquist and Gregory P. Miller; and Emin Oroudjev and Helen G. Hansma of the University of California-Santa Barbara Department of Physics. The study was supported by grants from the National Science Foundation and the Swedish Research Council.

COMMENT: Eric Kool, Chemistry: (650) 724-4741, kool@stanford.edu

Mark Shwartz | EurekAlert!
Further information:
http://www.stanford.edu/news/
http://news.stanford.edu
http://www.stanford.edu/dept/news/html/releases.html

More articles from Life Sciences:

nachricht Newly designed molecule binds nitrogen
23.02.2018 | Julius-Maximilians-Universität Würzburg

nachricht Atomic Design by Water
23.02.2018 | Max-Planck-Institut für Eisenforschung GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Attoseconds break into atomic interior

A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.

In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...

Im Focus: Good vibrations feel the force

A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.

By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...

Im Focus: Developing reliable quantum computers

International research team makes important step on the path to solving certification problems

Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Basque researchers turn light upside down

23.02.2018 | Physics and Astronomy

Finnish research group discovers a new immune system regulator

23.02.2018 | Health and Medicine

Attoseconds break into atomic interior

23.02.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>