Posts belonging to Category genetics



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.

Source: https://www.mrc.ac.uk/

How To Detect Cancer With a Urine Test

Researchers centered at Nagoya University (Japan) develop a nanowire device able to detect microscopic levels of urinary markers potentially implicated in cancerCells communicate with each other through a number of different mechanisms. Some of these mechanisms are well-known: in animals, for example, predatory threats can drive the release of norepinephrine, a hormone that travels through the bloodstream and triggers heart and muscle cells to initiate a “fight-or-flight” response. A far less familiar mode of cellular transport is the extracellular vesicle (EV). EVs can be thought of as small “chunks” of a cell that are able to pinch off and circulate throughout the body to deliver messenger cargo to other cells. These messengers have become increasingly recognized as crucial mediators of cell-to-cell communication.

In a new study reported in Science Advances, researchers centered at Nagoya University have developed a novel medical device that can efficiently capture these EVs, and potentially use them to screen for cancer.

CLICK ON THE IMAGE TO ENJOY THE VIDEO

EVs are potentially useful as clinical markers. The composition of the molecules contained in an EV may provide a diagnostic signature for certain diseases,” lead author Takao Yasui explains. “The ongoing challenge for physicians in any field is to find a non-invasive diagnostic tool that allows them to monitor their patients on a regular basis–for example, a simple urine test.”

Among the many molecules EVs have been found to harbor are microRNAs, which are short pieces of ribonucleic acid that play diverse roles in normal cellular biology. Critically, the presence of certain microRNAs in urine might serve as a red flag for serious conditions such as bladder and prostate cancer. While this important cargo could therefore theoretically aid physicians in cancer diagnoses, there are still many technological hurdles that need to be overcome. One such hurdle: finding a feasible method to capture EVs in sufficient quantities to analyze them in a routine clinical setting.

The content of EVs in urine is extremely low, at less than 0.01% of the total fluid volume. This is a major barrier to their diagnostic utility,” Yasui notes. “Our solution was to embed zinc oxide nanowires into a specialized polymer to create a material that we believed would be highly efficient at capturing these vesicles. Our findings suggest that the device is indeed quite efficient. We obtained a collection rate of over 99%, surpassing ultracentrifugation as well as other methods that are currently being used in the field.

Source: http://en.nagoya-u.ac.jp/

Paraplegic Rats Walk After Stem Cell Treatment

Engineered tissue containing human stem cells has allowed paraplegic rats to walk independently and regain sensory perception. The implanted rats also show some degree of healing in their spinal cords. The research, published in Frontiers in Neuroscience, demonstrates the great potential of stem cellsundifferentiated cells that can develop into numerous different types of cells—to treat spinal cord injury.

CLICK ON THE IMAGE TO ENJOY VIDEO

Spinal cord injuries often lead to paraplegia. Achieving substantial recovery following a complete tear, or transection, is an as-yet unmet challenge.

Led by Dr. Shulamit Levenberg, of the Technion-Israel Institute of Technology, the researchers implanted human stem cells into rats with a complete spinal cord transection. The stem cells, which were derived from the membrane lining of the mouth, were induced to differentiate into support cells that secrete factors for neural growth and survival.

The work involved more than simply inserting stem cells at various intervals along the spinal cord. The research team also built a three-dimensional scaffold that provided an environment in which the stem cells could attach, grow and differentiate into support cells. This engineered tissue was also seeded with human thrombin and fibrinogen, which served to stabilize and support neurons in the rat’s spinal cord.

Rats treated with the engineered tissue containing stem cells showed higher motor and sensory recovery compared to control rats. Three weeks after introduction of the stem cells, 42% of the implanted paraplegic rats showed a markedly improved ability to support weight on their hind limbs and walk. 75% of the treated rats also responded to gross stimuli to the hind limbs and tail.

In contrast, control paraplegic rats that did not receive showed no improved mobility or sensory responses.

In addition, the lesions in the spinal cords of the treated rats subsided to some extent. This indicates that their spinal cords were healing.

Source: https://medicalxpress.com/

How To Trap DNA molecules With Your Smartphone

Researchers from the University of Minnesota College of Science and Engineering have found yet another remarkable use for the wonder material graphenetiny electronictweezers” that can grab biomolecules floating in water with incredible efficiency. This capability could lead to a revolutionary handheld disease diagnostic system that could be run on a smart phoneGraphene, a material made of a single layer of carbon atoms, was discovered more than a decade ago and has enthralled researchers with its range of amazing properties that have found uses in many new applications from microelectronics to solar cells. The graphene tweezers developed at the University of Minnesota are vastly more effective at trapping particles compared to other techniques used in the past due to the fact that graphene is a single atom thick, less than 1 billionth of a meter.

The physical principle of tweezing or trapping nanometer-scale objects, known as dielectrophoresis, has been known for a long time and is typically practiced by using a pair of metal electrodes. From the viewpoint of grabbing molecules, however, metal electrodes are very blunt. They simply lack the “sharpness” to pick up and control nanometer-scale objects.

Graphene is the thinnest material ever discovered, and it is this property that allows us to make these tweezers so efficient. No other material can come close,” said research team leader Sang-Hyun Oh, a Professor at the University of Minnesota. “To build efficient electronic tweezers to grab biomolecules, basically we need to create miniaturized lightning rods and concentrate huge amount of electrical flux on the sharp tip. The edges of graphene are the sharpest lightning rods.

The team also showed that the graphene tweezers could be used for a wide range of physical and biological applications by trapping semiconductor nanocrystals, nanodiamond particles, and even DNA molecules. Normally this type of trapping would require high voltages, restricting it to a laboratory environment, but graphene tweezers can trap small DNA molecules at around 1 Volt, meaning that this could work on portable devices such as mobile phones.

The research study has been published  in Nature Communications.

Source: https://cse.umn.edu/

Artificial Intelligence Chip Analyzes Molecular-level Data In Real Time

Nano Global, an Austin-based molecular data company, today announced that it is developing a chip using intellectual property (IP) from Arm, the world’s leading semiconductor IP company. The technology will help redefine how global health challenges – from superbugs to infectious diseases, and cancer are conquered.

The pioneering system-on-chip (SoC) will yield highly-secure molecular data that can be used in the recognition and analysis of health threats caused by pathogens and other living organisms. Combined with the company’s scientific technology platform, the chip leverages advances in nanotechnology, optics, artificial intelligence (AI), blockchain authentication, and edge computing to access and analyze molecular-level data in real time.

In partnership with Arm, we’re tackling the vast frontier of molecular data to unlock the unlimited potential of this universe,” said Steve Papermaster, Chairman and CEO of Nano Global. “The data our technology can acquire and process will enable us to create a safer and healthier world.”

We believe the technology Nano Global is delivering will be an important step forward in the collective pursuit of care that improves lives through the application of technology,” explained Rene Haas, executive vice president and president of IPG, Arm. “By collaborating with Nano Global, Arm is taking an active role in developing and deploying the technologies that will move us one step closer to solving complex health challenges.”

Additionally, Nano Global will be partnering with several leading institutions, including Baylor College of Medicine and National University of Singapore, on broad research initiatives in clinical, laboratory, and population health environments to accelerate data collection, analysis, and product development.
The initial development of the chip is in process with first delivery expected by 2020. The company is already adding new partners to their platform.

Source: https://nanoglobal.com/
AND
www.prnewswire.com

New Genetic And Stem-Cell Technology To Grow Sheets Of Skin

Somewhere in Germany’s Ruhr valley, a nine-year-old boy is doing what children do: playing football, joking around with friends and going to school. Two years ago, he was confined to a hospital bed, dying of a rare and cruel genetic skin disease. The boy had junctional epidermolysis bullosa, or JEB. He, like other people with the disease, carried a mutation in a gene that controls the integrity of the skin. Doctors could only try to ease his suffering as some 80% of his skin simply fell away.

A team of Italian researchers came to his aid by combining stem-cell techniques with gene therapy. As a young scientist at Harvard Medical School in Boston, Massachusetts, in the 1980s, Michele De Luca — the lead author of the new study — watched pioneers in skin regeneration learn to grow small sheets of skin from cells taken from burns patients, and to use them in grafts. He extended the work in Italy, applying new genetic and stem-cell technologies. He developed ways to generate stem cells from human skin, replace disease-causing genes in them and grow sheets of healthy skin on scaffolds in the lab.

He chose JEB for his first clinical trial, which he registered with the Italian Medicines Agency in 2002. Four years later, he reported his first success, in which he created healthy skin patches from biopsies to replace small areas of sloughed-off skin on the legs of a patient with a form of JEB (F. Mavilio et al. Nature Med. 12, 1397–1402; 2006). New European Commission regulations introduced in 2007 required him to pause the project while he created facilities adhering to ‘good manufacturing practices’ (GMPs) and a spin-off company to meet the demands for strengthened oversight of cell-based therapies.

Having a company refocused his team’s attention on a different type of stem-cell therapy, one likely to yield a product for the market faster. Holoclar, a treatment that replaces the eye’s cornea in a form of blindness, became the world’s first commercial stem-cell therapy in 2015.

A few months later, at the University of Modena, De Luca got a call out of the blue from doctors in Germany who were trying to treat the little boy. Because the therapy had been in a clinical trial, albeit one on hold at the time, and because De Luca could provide GMP services, German regulatory authorities quickly approved the one-off compassionate use of the JEB therapy. Surgeons in Germany sent a skin biopsy to Modena, and two major skin transplants followed. Six months after the initial biopsy, the boy returned to school. During the many months since, he has not had so much as a blister, and loves to show off his ‘new skin’. By their nature, highly personalized treatments using gene therapies and products derived from an individual’s stem cells are likely to be applicable to only a subset of patients.

Scientists and clinicians have presented the details of the recovery in Nature (T. Hirsch et al.Nature http://dx.doi.org/10.1038/nature24487; 2017). This major clinical development was based on decades of basic research. The clinical data gathered during 21 months of follow-up after the boy’s treatment have also led to major insights into human skin biology, as discussed in an accompanying News & Views (M. Aragona and C. Blanpain Naturehttp://dx.doi.org/10.1038/nature24753; 2017). For example, normal regeneration of the epidermis is directed by only a few stem-cell clones that can self-renew.

Source: http://www.nature.com/

Acupuncture And Nanotechnology Married To Cure Cancer

DGIST (Daegu Gyeongbuk Institute of Science and Technology) in South Korea announced that Professor Su-Il In’s research team from the department of Energy Science and Engineering has presented the possibility of cancer treatment, including colorectal cancer, using acupuncture needles that employ nanotechnology for the first time in the world.

The research team of Professor Su-Il In, through joint research with Dr. Eunjoo Kim of Companion Diagnostics & Medical Technology Research Group at DGIST and Professor Bong-Hyo Lee’s research team from the College of Oriental Medicine at Daegu Haany University, has published a study showing that the molecular biologic indicators related to anticancer effects are changed only by the treatment of acupuncture, which is widely used in oriental medicine.

In oriental medicine, treatment using acupuncture needles has been commonly practiced for thousands of years in the fields of treating musculoskeletal disorders, pain relief, and addiction relief. Recently, it has emerged as a promising treatment for brain diseases, gastrointestinal disorders, nausea, and vomiting, and studies are under way to use acupuncture to treat severe diseases.

SURFACE IMAGES OF (A) CONVENTIONAL ACUPUNCTURE NEEDLE (CN) AND, (B) THE NANOPOROUS ACUPUNCTURE NEEDLE (PN) WITH ITS (C AND D) HIGH RESOLUTION IMAGES

Not only that, Professor In’s team discovered that acupuncture needles can be used for cancer treatment which is difficult to treat in modern medicine. In this study, the researchers developed nanoporous needles with microscopic holes in the surface of the needles ranging from nanopores (nm = one billionth of a meter) to micrometers (μm = one millionth of a meter) by applying relatively simple electrochemical nanotechnology. By increasing the surface area of the needle by a factor of ten, the nanoporous needles doubled the electrophysiological signal generation function by needle stimulus.

As a result of AOM administration in rats, the rats receiving periodic acupuncture treatment with nanoporous needles were found to have a much lower incidence of abnormal vascular clusters as a precursor to colorectal cancer in the initiation stage than those in the control group.

Source: https://www.eurekalert.org/

Editing Genes In Human Embryos

Two new CRISPR tools overcome the scariest parts of gene editing.The ability to edit RNA and individual DNA base pairs will make gene editing much more precise. Several years ago, scientists discovered a technique known as CRISPR/Cas9, which allowed them to edit DNA more efficiently than ever before.
Since then, CRISPR science has exploded; it’s become one of the most exciting and fast-moving areas of research, transforming everything from medicine to agriculture and energy. In 2017 alone, more than 14,000 CRISPR studies were published.

But here’s the thing: CRISPR, while a major leap forward in gene editing, can still be a blunt instrument. There have been problems with CRISPR modifying unintended gene targets and making worrisome, and permanent, edits to an organism’s genome. These changes could be passed down through generations, which has raised the stakes of CRISPR experiments — and the twin specters of “designer babies” and genetic performance enhancers — particularly when it comes to editing genes in human embryos.
So while CRISPR science is advancing quickly, scientists are still very much in the throes of tweaking and refining their toolkit. And on Wednesday, researchers at the Broad Institute of MIT and Harvard launched a coordinated blitz with two big reports that move CRISPR in that safer and more precise direction.
In a paper published in Science, researchers described an entirely new CRISPR-based gene editing tool that targets RNA, DNA’s sister, allowing for transient changes to genetic material. In Nature, scientists described how a more refined type of CRISPR gene editing can alter a single bit of DNA without cutting it — increasing the tool’s precision and efficiency.

The first paper, out Wednesday in Science, describes a new gene editing system. This one, from researchers at MIT and Harvard, focuses on tweaking human RNA instead of DNA.

Our cells contain chromosomes made up of chemical strands called DNA, which carry genetic information. Those genes have recipes for proteins that lead to a bunch of different traits. But to carry out the instructions in any one recipe, DNA needs another type of genetic material called RNA to get involved.

RNA is ephemeral: It acts like a middleman, or a messenger. For a gene to become a protein, that gene has to be transcribed into RNA in the cell, and the RNA is then read to make the protein. If the DNA is permanent — the family recipe book passed down through generations — the RNA is like your aunt’s scribbled-out recipe on a Post-It note, turning up only when it’s needed and disappearing again.

With the CRISPR/Cas9 system, researchers are focused on editing DNA. (For more on how that system works, read this Vox explainer.) But the new Science paper describes a novel gene editing tool called REPAIR that’s focused on using a different enzyme, Cas13, to edit that transient genetic material, the RNA, in cells. REPAIR can target specific RNA letters, or nucleosides, that are involved in single-base changes that regularly cause disease in humans.

This is hugely appealing for one big reason: With CRISPR/Cas9, the changes to the genome, or the cell’s recipe book, are permanent. You can’t undo them. With REPAIR, since researchers can target single bits of ephemeral RNA, the changes they make are transient, even reversible. So this system could fix genetic mutations without actually touching the genome (like throwing away your aunt’s Post-It note recipe without adding it to the family recipe book).

Source: https://www.vox.com/

Gene Researchers Have Created Green Mice

These are no Frankenstein mice. Their green feet come courtesy of a fluorescent green jelly fish gene added to their own genome. This allows a team of British scientists to test out gene editing using CRISPR-Cas9 technology.

CLICK ON THE IMAGE TO ENJOY THE VIDEO

“We take what were or would have been green embryos and we make them into non-green embryos, so it’s a really great way of demonstrating the method“, said Dr. Anthony Perry, reproductive biologist at the University of Bath.

The technique uses the ribonucleic acid molecule CRISPR together with the Cas9 protein enzyme. CRISPR guides the Cas9 protein to a defective part of a genome where it acts like molecular scissors to cut out a specific part of the DNA. This could revolutionise how we treat diseases with a genetic component, like sickle cell anaemia. The technique is being pioneered in the U.S.
We now have a technology that allows correction of a sequence that would lead to normally functioning cells. And I think you know the opportunities with this are really exciting and really profound. There are many diseases that are have known genetic causes that we now have in principle a way to cure,“explains Jennifer Doudna, Professor of cell biology at the University of Berkeley.
Last year two teams of U.S. based scientists used CRISPR-Cas9 technology in mice to correct the genetic mutation that causes sickle cell disease. Although researchers aren’t yet close to using CRISPR-Cas9 to edit human embryos for implantation into the womb – some are already warning against it.

Dr David King, Director of  Human Genetics Alert, comments: “It will immediately create this new form of what we call consumer eugenics, that’s to say eugenics driven by the free market and consumer preferences in which people choose the cosmetic characteristics and the abilities of their children and try to basically enhance their children to perform better than other people’s children.” Other potential applications of the technology could be to make food crops and livestock animal species disease-resistant. The British team say CRISPR-Cas9 presents a golden opportunity to prevent genetic disease.

Source: http://www.reuters.com/
A
ND
http://www.bath.ac.uk/

How To Fix Duchenne Muscular Dystrophy

Scientists at the University of California, Berkeley, have engineered a new way to deliver CRISPR-Cas9 gene-editing technology inside cells and have demonstrated in mice that the technology can repair the mutation that causes Duchenne muscular dystrophy, a severe muscle-wasting disease. A new study shows that a single injection of CRISPR-Gold, as the new delivery system is called, into mice with Duchenne muscular dystrophy led to an 18-times-higher correction rate and a two-fold increase in a strength and agility test compared to control groups.

Since 2012, when study co-author Jennifer Doudna, a professor of molecular and cell biology and of chemistry at UC Berkeley, and colleague Emmanuelle Charpentier, of the Max Planck Institute for Infection Biology, repurposed the Cas9 protein to create a cheap, precise and easy-to-use gene editor, researchers have hoped that therapies based on CRISPR-Cas9 would one day revolutionize the treatment of genetic diseases. Yet developing treatments for genetic diseases remains a big challenge in medicine. This is because most genetic diseases can be cured only if the disease-causing gene mutation is corrected back to the normal sequence, and this is impossible to do with conventional therapeutics.

CRISPR/Cas9, however, can correct gene mutations by cutting the mutated DNA and triggering homology-directed DNA repair. However, strategies for safely delivering the necessary components (Cas9, guide RNA that directs Cas9 to a specific gene, and donor DNA) into cells need to be developed before the potential of CRISPR-Cas9-based therapeutics can be realized. A common technique to deliver CRISPR-Cas9 into cells employs viruses, but that technique has a number of complications. CRISPR-Gold does not need viruses.

In the new study, research lead by the laboratories of Berkeley bioengineering professors Niren Murthy and Irina Conboy demonstrated that their novel approach, called CRISPR-Gold because gold nanoparticles are a key component, can deliver Cas9 – the protein that binds and cuts DNA – along with guide RNA and donor DNA into the cells of a living organism to fix a gene mutation.

CRISPR-Gold is the first example of a delivery vehicle that can deliver all of the CRISPR components needed to correct gene mutations, without the use of viruses,” Murthy said.

The study was published in the journal Nature Biomedical Engineering.

Source: http://news.berkeley.edu/

Nanogels For Heart Attack Patients

Heart disease and heart-related illnesses are a leading cause of death around the world, but treatment options are limited. Now, one group reports in ACS Nano that encapsulating stem cells in a nanogel could help repair damage to the heart.

Myocardial infarction, also known as a heart attack, causes damage to the muscular walls of the heart. Scientists have tried different methods to repair this damage. For example, one method involves directly implanting stem cells in the heart wall, but the cells often don’t take hold, and sometimes they trigger an immune reaction. Another treatment option being explored is injectable hydrogels, substances that are composed of water and a polymer. Naturally occurring polymers such as keratin and collagen have been used but they are expensive, and their composition can vary between batches. So Ke Cheng, Hu Zhang, Jinying Zhang and colleagues wanted to see whether placing stem cells in inexpensive hydrogels with designed tiny pores that are made in the laboratory would work.

The team encapsulated stem cells in nanogels, which are initially liquid but then turn into a soft gel when at body temperature. The nanogel didn’t adversely affect stem cell growth or function, and the encased stem cells didn’t trigger a rejection response. When these enveloped cells were injected into mouse and pig hearts, the researchers observed increased cell retention and regeneration compared to directly injecting just the stem cells. In addition, the heart walls were strengthened. Finally, the group successfully tested the encapsulated stem cells in mouse and pig models of myocardial infarction.

Source: https://www.acs.org/
A
ND
https://global.ncsu.edu/

Rapid, Cheap Liver Cancer Test

University of Utah researchers say they are designing a diagnostic method that will be able to accurately identify signs of liver cancer within minutes, saving critical time for patients of the stealthy disease. The new type of test could forever change how people screen for the disease, said Marc Porter, a U. chemical engineering and chemistry professor who is leading the research along with Dr. Courtney Scaife, a surgeon who both practices and teaches surgery for the university. Porter said the long-term vision is for the tool itself to become as automatic and portable as a pregnancy test, though additional technology — called a spectrometer — is currently needed to precisely measure the results of the test.

A small domino-sized cartridge holds a membrane for a new field test for liver cancer developed by researchers from the University of Utah. The test doesn’t involve sending a specimen to a blood lab and cuts the wait time for results from two weeks to two minutes. It can be administered wherever the patient is, which will be valuable for developing nations with little access to hospitals.

It’s really compact, it’s simple and low cost,” he said of the test kit.

Liver cancer is difficult to survive because typically it is highly developed by the time symptoms show up, Porter said. It is the second deadliest form of cancer worldwide, resulting in about 788,000 deaths in 2015, according to the World Health Organization. “All too often, the cancer is diagnosed past when you can actually have surgical intervention,” Porter said.

Currently, a blood test taken to determine the presence of liver cancer is usually sent to a lab offsite, where it takes days or even up to two weeks to test and return, said Vincent Horiuchi, spokesman for the U.’s College of Engineering. Those days are precious time that is lost in the fight against the disease, he said.

Source: https://unews.utah.edu/