Alcohol Damages DNA In Stem Cells

Scientists have shown how alcohol damages DNA in stem cells, which may help to explain how drinking alcohol is linked to an increased risk of cancer, according to research led by scientists from the MRC Laboratory of Molecular Biology (UK)  and part-funded by Cancer Research UK. Much previous research looking at the precise ways in which alcohol causes cancer has been done in cell cultures. But in this study, published in Nature, researchers used mice to show how alcohol exposure leads to permanent genetic damage.

The scientists gave diluted alcohol, chemically known as ethanol, to mice. They then used chromosome analysis and DNA sequencing to examine the genetic damage caused by acetaldehyde, a harmful chemical produced when the body processes alcohol. They found that acetaldehyde can break and damage DNA within blood stem cells leading to rearranged chromosomes and permanently altering the DNA sequences within these cells. It is important to understand how the DNA blueprint within stem cells is damaged, because when healthy stem cells become faulty they can give rise to cancer.

Some cancers develop due to DNA damage in stem cells. While some damage occurs by chance, our findings suggest that drinking alcohol can increase the risk of this damage,” said Professor Ketan Patelopens in new window, lead author of the study and scientist, part-funded by Cancer Research UK, at the MRC Laboratory of Molecular Biology.

The study also examined how the body tries to protect itself against damage caused by alcohol. The first line of defence is a family of enzymes called aldehyde dehydrogenases (ALDH). These enzymes break down harmful acetaldehyde into acetate, which our cells can use as a source of energy.

Worldwide, millions of people, particularly those from South East Asia, either lack these enzymes or carry faulty versions of them. So, when they drink, acetaldehyde builds up which causes a flushed complexion, and also leads to them feeling unwell.

In the study, when mice lacking the critical ALDH enzyme ALDH2 – were given alcohol, it resulted in four times as much DNA damage in their cells compared to mice with the fully functioning ALDH2 enzyme.


How To Read DNA Sequences In One Second

Despite having a diameter tens of thousands of times smaller than a human hair, nanopores could be the next big thing in DNA sequencing. By zipping DNA molecules through these tiny holes, scientists hope to one day read off genetic sequences in the blink of an eye. Now, researchers from Brown University have taken the potential of nanopore technology one step further. They have combined a nanopore with a tiny cage capable of trapping and holding a single DNA strand after it has been pulled through the pore. While caged, biochemical experiments can be performed on the strand, which can then be zipped back through the nanopore to look at how the strand has changed.

Nanopore1How the nanoscale cage works? An electrical field draws a strand of DNA in by the smaller hole, bottom, but the curled DNA cannot exit through the larger hole, top. After experimental procedures, a reversed electrical field draws the DNA strand back out of the lower hole, allowing before and after comparison

We see this as a very interesting enabling technique,” said Derek Stein, associate professor of physics and engineering at Brown, who helped develop the technology with his graduate students. “It allows you for the first time to look at the same molecule before and after any kind of chemical reaction that may have taken place.”

A paper describing the device is published in Nature Communications.


How To Read DNA At High-Speed

Berkeley Researchers Create Unique Graphene Nanopores with Optical Antennas for DNA Sequencing.
High-speed reading of the genetic code should get a boost with the creation of the world’s first graphene nanoporespores measuring approximately 2 nanometers in diameter – that feature a “built-inoptical antenna. Researchers with Berkeley Lab and the University of California (UC) Berkeley have invented a simple, one-step process for producing these nanopores in a graphene membrane using the photothermal properties of gold nanorods.
graphene nanopore
Schematic drawing of graphene nanopore with self-integrated optical antenna (gold) that enhances the optical readout signal (red) of DNA as it passes through a graphene nanopore

With our integrated graphene nanopore with plasmonic optical antenna, we can obtain direct optical DNA sequence detection,” says Luke Lee, the Arnold and Barbara Silverman Distinguished Professor at UC Berkeley. “We believe our approach opens new avenues for simultaneous electrical and optical nanopore DNA sequencing and for regulating DNA translocation,” says Zettl, who is also a member of the Kavli Energy Nanoscience Institute (Kavli ENSI).


Fast DNA Sequencing Under A Thousand Dollars

Gene-based personalized medicine has many possibilities for diagnosis and targeted therapy, but one big bottleneck: the expensive and time-consuming DNA-sequencing process. Now, researchers at the University of Illinois at Urbana-Champaign have found that nanopores in the material molybdenum disulfide (MoS2) could sequence DNA more accurately, quickly and inexpensively than anything yet available.
One of the big areas in science is to sequence the human genome for under $1,000, the ‘genome-at-home,’” said Narayana Aluru, a professor of mechanical science and engineering at the U. of I. who led the study. “There is now a hunt to find the right material. We’ve used MoS2 for other problems, and we thought, why don’t we try it and see how it does for DNA sequencing?” As it turns out, MoS2 outperforms all other materials used for nanopore DNA sequencing – even graphene.
A nanopore is a very tiny hole drilled through a thin sheet of material. The pore is just big enough for a DNA molecule to thread through. An electric current drives the DNA through the nanopore, and the fluctuations in the current as the DNA passes through the pore tell the sequence of the DNA, since each of the four letters of the DNA alphabet – A, C, G and T – are slightly different in shape and size.

DNA through nanopores

A DNA molecule passes through a nanopore in a sheet of molybdenum disulfide, a material that researchers have found to be better than graphene at reading the DNA sequence
The ultimate goal of this research is to make some kind of home-based or personal DNA sequencing device,” Barati Farimani said. “We are on the path to get there, by finding the technologies that can quickly, cheaply and accurately identify the human genome. Having a map of your DNA can help to prevent or detect diseases in the earliest stages of development. If everybody can cheaply sequence so they can know the map of their genetics, they can be much more alert to what goes on in their bodies.


Get Your DNA In 3 Minutes

Take a swab of saliva from your mouth and within minutes your DNA could be ready for analysis and genome sequencing with the help of a new device. Now University of Washington engineers and NanoFacture, a Bellevue, Wash., company, have created a device that can extract human DNA from fluid samples in a simpler, more efficient and environmentally friendly way than conventional methods. The device will give hospitals and research labs a much easier way to separate DNA from human fluid samples, which will help with genome sequencing, disease diagnosis and forensic investigations.

Hand-held device for extracting DNA
It’s very complex to extract DNA,” said Jae-Hyun Chung, a UW associate professor of mechanical engineering who led the research. “When you think of the current procedure, the equivalent is like collecting human hairs using a construction crane.”
The small, box-shaped kit now is ready for manufacturing, then eventual distribution to hospitals and clinics.


Entire Genome Sequencing in Minutes?

The claim that nanopore technology is on the verge of making DNA analysis so fast and cheap that a person’s entire genome could be sequenced in just minutes and at a fraction of the cost of available commercial methods, has resulted in overwhelming academic, industrial, and global interest. But a review by Northeastern University – Boston – physicist Meni Wanunu, published in a special issue on nanopore sequencing in Physics of Life Reviews, questions whether the remaining technical hurdles can be overcome to create a workable, easily produced commercial device.

Earlier this year Oxford Nanopore Technologies, one of the pioneering companies of sequencing discoveries, announced that they expect nanopore strand sequencing to achieve a 15-minute genome by 2014 at a cost of $1,500. This is a far cry from the $10 million it cost to sequence an entire genome just 5 years ago. Since the idea of nanopore sequencing was first proposed in the mid 1990s, huge advances have been made. The basic idea is exceedingly simple: a single thread of DNA is passed through a tiny molecule-sized hole—or nanopore—and the various DNA bases are identified in sequence as they move through the pore.

But according to Wanunu, the reality of manipulating technology based on pores so tiny that 25,000 of them can fit side by side on a human hair has proved a daunting task. The main challenge has been to slow the process down and control the movement of the DNA strand through the pore at a rate slow enough to make individual DNA bases readable and usable. A new approach using enzyme-controlled movement, developed to overcome this problem, has its own drawbacks including poor enzyme activity resulting in limited processivity and uncontrolled forward-reverse motion.