RNA editing and cancer

Genomic mutations in key genes are known to drive tumorigenesis and have been the focus of much attention in recent years. However, genetic content also may change farther downstream.

RNA editing alters the mRNA sequence from its genomic blueprint in a dynamic and flexible way. A few isolated cases of editing alterations in cancer have been reported previously.

Researchers provide a transcriptome-wide characterization of RNA editing across hundreds of cancer samples from multiple cancer tissues, and show that A-to-I editing and the enzymes mediating this modification are significantly altered, usually elevated, in most cancer types.

Increased editing activity is found to be associated with patient survival. As is the case with somatic mutations in DNA, most of these newly introduced RNA mutations are likely passengers, but a few may serve as drivers that may be novel candidates for therapeutic and diagnostic purposes.

http://www.cell.com/cell-rep…/abstract/S2211-1247(15)00993-6

A Surprise Source of Life’s Code

Emerging data suggests the seemingly impossible — that mysterious new genes arise from “junk” DNA.

Genes, like people, have families — lineages that stretch back through time, all the way to a founding member. That ancestor multiplied and spread, morphing a bit with each new iteration.

For most of the last 40 years, scientists thought that this was the primary way new genes were born — they simply arose from copies of existing genes. The old version went on doing its job, and the new copy became free to evolve novel functions.

Certain genes, however, seem to defy that origin story. They have no known relatives, and they bear no resemblance to any other gene. They’re the molecular equivalent of a mysterious beast discovered in the depths of a remote rainforest, a biological enigma seemingly unrelated to anything else on earth.

The mystery of where these orphan genes came from has puzzled scientists for decades. But in the past few years, a once-heretical explanation has quickly gained momentum — that many of these orphans arose out of so-called junk DNA, or non-coding DNA, the mysterious stretches of DNA between genes. “Genetic function somehow springs into existence,” said David Begun, a biologist at the University of California, Davis.

This metamorphosis was once considered to be impossible, but a growing number of examples in organisms ranging from yeast and flies to mice and humans has convinced most of the field that these de novo genes exist. Some scientists say they may even be common. Just last month, research presented at the Society for Molecular Biology and Evolution in Vienna identified 600 potentially new human genes. “The existence of de novo genes was supposed to be a rare thing,” said Mar Albà, an evolutionary biologist at the Hospital del Mar Research Institute in Barcelona, who presented the research. “But people have started seeing it more and more.”

Researchers are beginning to understand that de novo genes seem to make up a significant part of the genome, yet scientists have little idea of how many there are or what they do. What’s more, mutations in these genes can trigger catastrophic failures. “It seems like these novel genes are often the most important ones,” said Erich Bornberg-Bauer, a bioinformatician at the University of Münster in Germany.

The Orphan Chase

The standard gene duplication model explains many of the thousands of known gene families, but it has limitations. It implies that most gene innovation would have occurred very early in life’s history. According to this model, the earliest biological molecules 3.5 billion years ago would have created a set of genetic building blocks. Each new iteration of life would then be limited to tweaking those building blocks.
Yet if life’s toolkit is so limited, how could evolution generate the vast menagerie we see on Earth today? “If new parts only come from old parts, we would not be able to explain fundamental changes in development,” Bornberg-Bauer said.

The first evidence that a strict duplication model might not suffice came in the 1990s, when DNA sequencing technologies took hold. Researchers analyzing the yeast genome found that a third of the organism’s genes had no similarity to known genes in other organisms. At the time, many scientists assumed that these orphans belonged to families that just hadn’t been discovered yet. But that assumption hasn’t proven true. Over the last decade, scientists sequenced DNA from thousands of diverse organisms, yet many orphan genes still defy classification. Their origins remain a mystery.

In 2006, Begun found some of the first evidence that genes could indeed pop into existence from noncoding DNA. He compared gene sequences from the standard laboratory fruit fly, Drosophila melanogaster, with other closely related fruit fly species. The different flies share the vast majority of their genomes. But Begun and collaborators found several genes that were present in only one or two species and not others, suggesting that these genes weren’t the progeny of existing ancestors. Begun proposed instead that random sequences of junk DNA in the fruit fly genome could mutate into functioning genes.

Yet creating a gene from a random DNA sequence appears as likely as dumping a jar of Scrabble tiles onto the floor and expecting the letters to spell out a coherent sentence. The junk DNA must accumulate mutations that allow it to be read by the cell or converted into RNA, as well as regulatory components that signify when and where the gene should be active. And like a sentence, the gene must have a beginning and an end — short codes that signal its start and end.

In addition, the RNA or protein produced by the gene must be useful. Newly born genes could prove toxic, producing harmful proteins like those that clump together in the brains of Alzheimer’s patients. “Proteins have a strong tendency to misfold and cause havoc,” said Joanna Masel, a biologist at the University of Arizona in Tucson. “It’s hard to see how to get a new protein out of random sequence when you expect random sequences to cause so much trouble.” Masel is studying ways that evolution might work around this problem.

Another challenge for Begun’s hypothesis was that it’s very difficult to distinguish a true de novo gene from one that has changed drastically from its ancestors. (The difficulty of identifying true de novo genes remains a source of contention in the field.)

Ten years ago, Diethard Tautz, a biologist at the Max Planck Institute for Evolutionary Biology, was one of many researchers who were skeptical of Begun’s idea. Tautz had found alternative explanations for orphan genes. Some mystery genes had evolved very quickly, rendering their ancestry unrecognizable. Other genes were created by reshuffling fragments of existing genes.

Then his team came across the Pldi gene, which they named after the German soccer player Lukas Podolski. The sequence is present in mice, rats and humans. In the latter two species, it remains silent, which means it’s not converted into RNA or protein. The DNA is active or transcribed into RNA only in mice, where it appears to be important — mice without it have slower sperm and smaller testicles.

The researchers were able to trace the series of mutations that converted the silent piece of noncoding DNA into an active gene. That work showed that the new gene is truly de novo and ruled out the alternative — that it belonged to an existing gene family and simply evolved beyond recognition. “That’s when I thought, OK, it must be possible,” Tautz said.

A Wave of New Genes

Scientists have now catalogued a number of clear examples of de novo genes: A gene in yeast that determines whether it will reproduce sexually or asexually, a gene in flies and other two-winged insects that became essential for flight, and some genes found only in humans whose function remains tantalizingly unclear.
At the Society for Molecular Biology and Evolution conference last month, Albà and collaborators identified hundreds of putative de novo genes in humans and chimps — ten-fold more than previous studies — using powerful new techniques for analyzing RNA. Of the 600 human-specific genes that Albà’s team found, 80 percent are entirely new, having never been identified before.

Unfortunately, deciphering the function of de novo genes is far more difficult than identifying them. But at least some of them aren’t doing the genetic equivalent of twiddling their thumbs. Evidence suggests that a portion of de novo genes quickly become essential. About 20 percent of new genes in fruit flies appear to be required for survival. And many others show signs of natural selection, evidence that they are doing something useful for the organism.

In humans, at least one de novo gene is active in the brain, leading some scientists to speculate such genes may have helped drive the brain’s evolution. Others are linked to cancer when mutated, suggesting they have an important function in the cell. “The fact that being misregulated can have such devastating consequences implies that the normal function is important or powerful,” said Aoife McLysaght, a geneticist at Trinity College in Dublin who identified the first human de novo genes.
Promiscuous Proteins

De novo genes are also part of a larger shift, a change in our conception of what proteins look like and how they work. De novo genes are often short, and they produce small proteins. Rather than folding into a precise structure — the conventional notion of how a protein behaves — de novo proteins have a more disordered architecture. That makes them a bit floppy, allowing the protein to bind to a broader array of molecules. In biochemistry parlance, these young proteins are promiscuous.

Scientists don’t yet know a lot about how these shorter proteins behave, largely because standard screening technologies tend to ignore them. Most methods for detecting genes and their corresponding proteins pick out long sequences with some similarity to existing genes. “It’s easy to miss these,” Begun said.

That’s starting to change. As scientists recognize the importance of shorter proteins, they are implementing new gene discovery technologies. As a result, the number of de novo genes might explode. “We don’t know what things shorter genes do,” Masel said. “We have a lot to learn about their role in biology.”

Scientists also want to understand how de novo genes get incorporated into the complex network of reactions that drive the cell, a particularly puzzling problem. It’s as if a bicycle spontaneously grew a new part and rapidly incorporated it into its machinery, even though the bike was working fine without it. “The question is fascinating but completely unknown,” Begun said.

A human-specific gene called ESRG illustrates this mystery particularly well. Some of the sequence is found in monkeys and other primates. But it is only active in humans, where it is essential for maintaining the earliest embryonic stem cells. And yet monkeys and chimps are perfectly good at making embryonic stem cells without it. “It’s a human-specific gene performing a function that must predate the gene, because other organisms have these stem cells as well,” McLysaght said.
“How does novel gene become functional? How does it get incorporated into actual cellular processes?” McLysaght said. “To me, that’s the most important question at the moment.”

https://www.quantamagazine.org/20150818-a-surprise-source-…/

Parents’ bad habits can be passed on to their children genetically

There’s now overwhelming evidence that parents’ bad habits can be passed on to their children genetically, according to Australian researchers.

Image: Deva Studio/Shutterstock

Environmental factors and parents’ health before conception have more influence on a child’s future than previously thought, a paper published last week in Science by researchers from the University of Adelaide has found.

The authors conclude that there is now overwhelming evidence that sperm and eggs carry more than just genes - they are also coded with genetic memories that can affect the health of an embryo.

This means that parents' bad habits, such as poor diet or drinking too much alcohol, could be passed on to their children, even if they are healthy during pregnancy or shortly before conceiving.

"Many things we do in the lead up to conceiving is having an impact on the future development of the child - from the age of the parents, to poor diet, obesity, smoking and many other factors, all of which influence environmental signals transmitted into the embryo," Sarah Robertson, an author of the paper and Director of the University of Adelaide’s Robinson Research Institute,said in a press release.

"People used to think that it didn't matter, because a child represented a new beginning, with a fresh start. The reality is, we can now say with great certainty that the child doesn't quite start from scratch - they already carry over a legacy of factors from their parents' experiences that can shape development in the fetus and after birth. Depending on the situation, we can give our children a burden before they've even started life."

Over the past decade, scientists have been investigating the way that these memories and habits can be passed on to offspring, through a process known as epigenetics. This refers to the ability of environmental factors to turn the expression of genes on or off, without actually changing the DNA or genetic code. 

Now, the paper concludes, there is sufficient peer-reviewed research to claim that a baby’s health begins with parents long before conception.

Although, she stresses to Brad Crouch, from The Advertiser, genes are still the primary blueprint for a new child. “But this is at another level, it is the decoration of the gene, the icing on the cake if you like, a gift to offspring that gives them another layer of information about survival,” said Robertson.

Source: ScienceDaily

Mutations in a gene that helps to cope with stress could increase the risk of suicide

Researchers have found that mutations in a gene that helps to cope with stress could increase the risk of suicide. Now they will try to develop a blood test to predict the risk. 

Image: AfricaStudio/Shutterstock

Every 40 seconds someone in the world commits suicide. But a new discovery in the US by Johns Hopkins University researchers could help lower this statistic.

The researchers analysed 150 brain samples of deceased mentally ill and healthy people, including some of patients who had committed suicide. They discovered that all of those who had taken their lives had a mutation in the SKA2 gene.

This gene is expressed in the prefrontal cortex of the brain, and it determines how the brain reacts to stress hormones such as cortisol.

“If the gene’s function is impaired by a chemical change,” explains Caelainn Hogan from theWashington Post, “someone who is stressed won’t be able to shut down the effect of the stress hormone, which would be like having a faulty brake pad in a car for the fear centre of the brain, worsening the impact of even everyday stress.”

To confirm their results, the scientists analysed blood samples of 325 participants in the Johns Hopkins Center for Prevention Research Study, and found that those who had suicidal thoughts or had tried to commit suicide presented chemical alterations in the SKA2 gene.

And their blood test predicted with 80 to 90 percent accuracy whether a person had suicidal thoughts or had made an attempt to take their own life.

"We have found a gene that we think could be really important for consistently identifying a range of behaviours from suicidal thoughts to attempts to completions," psychiatrist and behavioural scientist Zachary Kaminsky, lead author of the study, said in a news release. "We need to study this in a larger sample but we believe that we might be able to monitor the blood to identify those at risk of suicide."

This study, which was published in the American Journal of Psychiatry, will help in the development of a blood tests that could predict if a person has mutations in the SKA2 gene and is prone to excess levels of stress and anxiety, which may lead to suicidal thoughts or attempts.

Sources: The Washington Post and ScienceDaily

The pursuit of happiness could be dictated by your genes

Financial stability, social connections and health have an impact on happiness levels, but scientists now say that your genes could play a key role too.

Image: Andresr/Shutterstock

A team of researchers led by economist Eugenio Proto from the University of Warwick in the UK wanted to know why Danes generally rank as the happiest people in the world. The 'happiness rankings' usually measure life-expectancy, living standartds, reported well-being and ecological footprint to assess which are the happiest countries on Earth.

In their study, published in the journal IZA as a discussion paper, they compared the genetic makeup of people in 131 countries to that of denizens of Denmark. And they have discovered that the greater the nation's genetic distance from Denmark, the lower their reported well-being,explains Kelly Dickerson from LiveScience. 

The researchers also looked at scientific literature that suggests there is a link between mental well-being and variations of the gene SLC6A4, which helps transport serotonin, a chemical that makes you feel good. Then they looked at genetic data from 30 countries to see which populations had more variations of this gene. 

“We looked at existing research which suggested that the long and short variants of this gene are correlated with different probabilities of clinical depression, although this link is still highly debated,” explains Proto in a press release. “The short version has been associated with higher scores on neuroticism and lower life satisfaction. Intriguingly, among the 30 nations included in the study, it is Denmark and the Netherlands that appear to have the lowest percentage of people with this short version.” 

To further prove their theory, Proto and his team looked at well-being surveys from a group of Americans and traced their genetic origins. Those who reported to be the happiest descended from immigrants from the happiest countries, including Denmark, the Netherlands, and Sweden.

The paper is controversial, but the researchers hope their data can help us and other scientists better understand why some countries consistently report high levels of happiness.

Last year Denmark, Norway, Switzerland, the Neatherlands and Sweden were ranked the top five happiest countries on Earth—Australia got the 10th place. 

Source: LiveScience via Business Insider

Estimating genetic influence on learning ability using DNA alone

"This is the first time we estimate genetic influence on learning ability using DNA alone. The study does not point to specific genes linked to literacy or numeracy, but rather suggests that genetic influence on complex traits, like learning abilities, and common disorders, like learning disabilities, is caused by many genes of very small effect size. The study also confirms findings from previous twin studies that genetic differences among children account for most of the differences between children in how easily they learn to read and to do maths. Children differ genetically in how easy or difficult they find learning, and we need to recognise, and respect, these individual differences. Finding such strong genetic influence does not mean that there is nothing we can do if a child finds learning difficult—heritability does not imply that anything is set in stone – it just means it may take more effort from parents, schools and teachers to bring the child up to speed."

Dr Chris Spencer (Oxford University), lead author said: "We're moving into a world where analysing millions of DNA changes, in thousands of individuals, is a routine tool in helping scientists to understand aspects of human biology. This study used the technique to help investigate the overlap in the genetic component of reading and maths ability in children. Interestingly, the same method can be applied to pretty much any human trait, for example to identify new links between diseases and disorders, or the way in which people respond to treatments."

DNA study on mummies suggests climate instability drove ancient Peruvians to migrate

"To gain a clearer understanding of early Nasca, Wari and Tiwanaku peoples living in various parts of what is now Peru, the researchers collected DNA samples from 207 mummies found in both coastal and mountainous parts of the region. Mitochondrial analysis and Bayesian modeling indicated that people that had been living near the coast began migrating to the mountains sometime around 640 BC. They also found evidence of a reverse migration as people from the mountains migrated towards the coast around 1200 AD."

How One Key Gene Could Cause Brain Disability In Children

Scientists first discovered that mutated TUBB5 genes may cause microcephaly in 2012 by manipulating brain development in unborn mice. They also examined three child patients with microcephaly. In a new study, published in the journal Human Molecular Genetics, the authors build upon the 2012 research, discovering the first direct evidence that the gene causes microcephaly in three human patients.

The work could have implications for disorders more common than microcephaly, such as autism or schizophrenia. "TUBB5 works like a type of scaffolding inside neurons, enabling them to shape their connections to other neurons, so it's essential for healthy brain development," said Dr. Julian Heng, of the Australian Regenerative Medicine Institute at Monash University, in a statement. "If the scaffolding is faulty, in this case of TUBB5 mutates, it can have serious consequences."

Gene editing could make humans resistant to HIV

A new genetic engineering tool can help give cells a rare mutation that prevents them from being infected with HIV.

Image: CDC

The technique, which is still in experimental stages, takes advantage of a rare mutation that makes one percent of people of European descent resistant to HIV.
Using a new “genome editing” tool, researchers are hoping to be able to insert the mutation into the cells of other people - and they’ve already proved the basic principles work using induced pluripotent stem cells (iPSCs), Peter Aldhous reports for New Scientist.
The new genome editing technique is much more precise than tradition forms of genetic engineering, as it places a sequence of gene into a pre-designated area of the genome, rather than at random locations.
By using this technique, researchers led by Yuet Kan from the University of California, San Francico, have managed to alter the genome of iPSCs, which can turn into any cell in the body. As predicted, when the scientists grew these iPSCs into white blood cells, they were resistant to HIV.
Their research is published in the Proceedings of the National Academy of Sciences.
The mutation they’re implanting causes people to carry two copies of a mutated gene for a protein called CCR5, which the HIV virus has to lock onto before it can invade white blood cells. The mutation prevents it from doing that.
The research was inspired by a man called Timothy Ray Brown, who was famously “cured” after receiving a bone marrow transplant from a naturally HIV-resistant person. This new technique would work in a similar way, but without the need for someone else’s bone marrow.
However, although it works in the lab, there is still a long way to go before the treatment could be used in humans. 
The researchers now plan to turn the iPSCs into blood-forming stem cells, which, when transplanted into a patient, would give rise to all the different types of blood cells - including the specific white blood cell attacked by HIV.
It’s a pretty exciting first step, and we can’t wait to see what happens next.

Source: New Scientist

People more likely to choose a spouse with similar DNA, research shows

Scientists already knew that people tend to marry others who have similar characteristics, including religion, age, race, income, body type and education, among others.
In the new study, published in the journal Proceedings of the National Academy of Sciences, scientists show that people also are more likely to pick mates who have similar DNA. While characteristics such as race, body type and even education have genetic components, this is the first study to look at similarities across the entire genome.
"It's well known that people marry folks who are like them," said Benjamin Domingue, lead author of the paper and a research associate at CU-Boulder's Institute of Behavioral Science. "But there's been a question about whether we mate at random with respect to genetics."
For the study, Domingue and his colleagues, including CU-Boulder Associate Professor Jason Boardman, used genomic data collected by the Health and Retirement Study, which is sponsored by the National Institute on Aging.
The researchers examined the genomes of 825 non-Hispanic white American couples. They looked specifically at single-nucleotide polymorphisms, which are places in their DNA that are known to commonly differ among humans.
The researchers found that there were fewer differences in the DNA between married people than between two randomly selected individuals. In all, the researchers estimated genetic similarity between individuals using 1.7 million single-nucleotide polymorphisms in each person's genome.
The researchers compared the magnitude of the genetic similarity between married people to the magnitude of the better-studied phenomenon of people with similar educations marrying, known as educational assortative mating. They found that the preference for a genetically similar spouse, known as genetic assortative mating, is about a third of the strength of educational assortative mating.
The findings could have implications for statistical models now used by scientists to understand genetic differences between human populations because such models often assume random mating.
The study also forms a foundation for future research that could explore whether similar results are found between married people of other races, whether people also choose genetically similar friends, and whether there are instances when people prefer mates whose DNA is actually more different rather than more similar.

Reconstructed ancient ocean reveals secrets about the origin of life

Researchers have published details about how the first organisms on Earth could have become metabolically active. The results permit scientists to speculate how primitive cells learned to synthesize their organic components -- the molecules that form RNA, lipids and amino acids. The findings also suggest an order for the sequence of events that led to the origin of life.

A reconstruction of Earth's earliest ocean in the laboratory revealed the spontaneous occurrence of the chemical reactions used by modern cells to synthesize many of the crucial organic molecules of metabolism (bottom pathway). Whether and how the first enzymes adopted the metal-catalyzed reactions described by the scientists remain to be established.

Credit: Molecular Systems Biology / Creative 

Your Low Tolerance For Pain Can Be Blamed On Your Genes

"Our study is quite significant because it provides an objective way to understand pain and why different individuals have different pain tolerance levels," study leader Tobore Onojjighofia said. "Identifying whether a person has these four genes could help doctors better understand a patient's perception of pain."

In the analysis, scientists found a greater prevalence of the DRD1gene variant among those who reported low pain perception, seen 33 percent more than otherwise. Likewise, the COMT and OPRK variants were found 25 percent and 19 percent more often among those with moderate pain compared to those with high pain. And the DRD2 variant appeared 25 percent more often among those with the highest pain perception compared to those with moderate pain. Onojjighofia presented the findings to the American Academy of Neurology’s annual meeting.

Zonkey, a lovely two-for-one hybrid of the zebra and the donkey

This is Ippo the zonkey, a lovely two-for-one hybrid of the zebra and the donkey. Ippo was born just four months ago at an animal reserve in Florence, Italy. Her parents’ unusual tryst occurred when her father, Martin the zebra, jumped the fence at his enclosure and entered an enclosure housing endangered Amiata donkeys. In the enclosure, Martin met Giada and, twelve months later, little Ippo was born!

Hybrids like Ippo are very rare. They combine various traits from both parent species – their overall appearance is more like that of the donkey, but they have striped legs and tummies and a wilder temperament than that of the donkey.

Unfortunately, like mules, hybrids like Ippo are often infertile because of different numbers of chromosome. However, there shouldn’t be any significant health issues that would prevent Ippo from living a long and fulfilling life. Given her unique story and appearance, she will probably be making a lot of new friends at her animal reserve in no time!

Breast stem cells could carry cancer

Researchers from Melbourne’s Walter and Eliza Hall Institute have discovered that breast stem cells and their ‘daughters’ have a much longer lifespan than previously thought, and are active in puberty and throughout life.
The longevity of breast stem cells and their daughters means that they could harbour genetic defects or damage that progress to cancer decades later, potentially shifting back the timeline of breast cancer development. The finding is also integral to identifying the ‘cells of origin’ of breast cancer and the ongoing quest to develop new treatments and diagnostics for breast cancer.
Breast stem cells were isolated in 2006 by Professor Jane Visvader and Professor Geoff Lindeman and their colleagues from the ACRF Stem Cells and Cancer division at the Walter and Eliza Hall Institute.
Now, in a project led by Dr Anne Rios and Dr Nai Yang Fu that tracked normal breast stem cells and their development the team has discovered that breast stem cells actively maintain breast tissue for most of the life of the individual and contribute to all major stages of breast development. The research was published in the journal Nature.
Professor Lindeman, who is also an oncologist at The Royal Melbourne Hospital, said discovering the long lifespan and programming of breast stem cells would have implications for identifying the cells of origin of breast cancers.
“Given that these stem cells – and their ‘daughter’ progenitor cells – can live for such a long time and are capable of self renewing, damage to their genetic code could lead to breast cancer 10 or 20 years later,” Professor Lindeman said. “This finding has important applications for our understanding of breast cancer. We hope that it will lead to the development of new treatment and diagnostic strategies in the clinic to help women with breast cancer in the future.”
Professor Visvader said understanding the hierarchy and development of breast cells was critical to identifying the cells that give rise to breast cancer, and how and why these cells become cancerous. “Without knowing the precise cell types in which breast cancer originates, we will continue to struggle in our efforts to develop new diagnostics and treatments for breast cancer, or developing preventive strategies,” Professor Visvader said.
Previous research from the institute team had already implicated some of these immature breast cells in cancer development. “In 2009, we showed that luminal progenitor cells, the daughters of breast stem cells, were the likely cell of origin for the aggressive BRCA1-associated basal breast cancers,” Professor Visvader said. “The meticulous work of Anne and Nai Yang, using state-of-the-art three-dimensional imaging, has significantly improved our understanding of normal breast development and will have future applications for breast cancer.”
The project should settle a debate that has been raging in the scientific field, confirming that breast stem cells were ‘true’ stem cells capable of renewing themselves and making all the cells of the mammary gland.
“Our team was amongst the first to isolate ‘renewable’ breast stem cells,” Professor Visvader said. “However the existence of a common stem cell that can create all the cells lining the breast ducts has been a contentious issue in the field. In this study we’ve proven that ancestral breast stem cells function in puberty and adulthood and that they give rise to all the different cell types that make up the adult breast.”
The research project was supported by the Australian National Health and Medical Research Council, Victorian Government, Australian Cancer Research Foundation, Qualtrough Research Fund, National Breast Cancer Foundation and Cure Cancer Australia.

Editor's Note: Original news release can be found here.

Scientists have created stem cells without using embryonic material AND without introducing genetic material!

Scientists have created stem cells without using embryonic material AND without introducing genetic material! 

While the testing has only included cells from mice, the approach could one day work for humans as well. 

The idea of taking individual cells to a point of near-death, either by subjecting them to acid or other unfavorable conditions, was inspired by other work with plants. Botanists have long been able to take injured plants and regrow them from a node.

How a living, beating heart is grown from stem cells.

Scientists are growing human hearts in laboratories, offering hope for millions of cardiac patients.

American researchers believe the artificial organs could start beating within weeks.

The experiment is a major step towards the first ‘grow-your-own’ heart, and could pave the way for  livers, lungs or kidneys to be made  to order.

The organs were created by removing muscle cells from donor organs to leave behind tough hearts of connective tissue.

Researchers then injected stem cells which multiplied and grew around the structure, eventually turning into healthy heart cells.

Dr Doris Taylor, an expert in regenerative medicine at the University of Minnesota in Minneapolis, said: ‘The hearts are growing, and we hope they will show signs of beating within the next weeks.

‘There are many hurdles to overcome to generate a fully functioning heart, but my prediction is that it may one day be possible to grow entire organs for transplant.’

Patients given normal heart transplants must take drugs to suppress their immune systems for the rest of their lives.

+2

This can increase the risk of high blood pressure, kidney failure and diabetes.

If new hearts could be made using a patient’s own stem cells, it is less likely they would be rejected. 

 

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The lab-grown organs have been created using these types of cells – the body’s immature ‘master cells’ which have the ability to turn into different types of tissue. The experiment follows a string of successes for researchers trying to create spare body parts for transplants.

In 2007, British doctors grew  a human heart valve using stem  cells taken from a patient’s  bone marrow. 

HOW TO GROW YOUR OWN HEART

• The donor heart is removed from the body; pig hearts may also be suitable.
• Detergents are then used to strip the cells from the heart leaving behind the protein skeleton or 'ghost heart'.
• Stem cells grown from cells taken from a patient are then added to the ghost heart.
• The stem cells then multiply and generate new heart cells. now all that is left is the hope that these will start beating.

A year later, scientists grew a beating animal heart for the first time.

Dr Taylor’s team have already created beating rat and pig hearts. Although they were too weak to be used in animals, the work was an important step towards tailor-made organs.

In their latest study, reported at the American College of Cardiology’s annual conference in New Orleans, researchers created new organs using human hearts taken from dead bodies.

The scientists stripped the  cells from the dead hearts with a powerful detergent, leaving ‘ghost heart’ scaffolds made from the protein collagen.

The ghost hearts were then injected with millions of stem cells, which had been extracted from patients and supplied with nutrients.

The stem cells ‘recognised’ the collagen heart structure and began to turn into heart muscle cells.

The hearts have yet to start beating – but if they do, they could be strong enough to pump blood.

However, the race to create a working heart faces many obstacles.

One of the biggest is getting enough oxygen to the organ through a complex network of blood vessels. Scientists also need to ensure the heart cells beat in time.

Dr Taylor told the Sunday Times: ‘We are a long way off creating a heart for transplant, but we think we’ve opened a door to building any organ for human transplant.’

Read more: http://www.dailymail.co.uk/health/article-1372938/Live-human-heart-grown-lab-using-stem-cells-potential-transplant-breakthrough.html#ixzz2sJyoUlKO

The world’s first genetically-modified humans have been created

The world’s first genetically-modified humans have been created, it was revealed on October 16, 2013
The disclosure that 30 healthy babies were born after a series of experiments in the United States provoked another furious debate about ethics.
So far, two of the babies have been tested and have been found to contain genes from three ‘parents’.
Fifteen of the children were born in the past three years as a result of one experimental program at the Institute for Reproductive Medicine and Science of St Barnabas in New Jersey.
The babies were born to women who had problems conceiving. Extra genes from a female donor were inserted into their eggs before they were fertilized in an attempt to enable them to conceive.
Genetic fingerprint tests on two one-year- old children confirm that they have inherited DNA from three adults –two women and one man.
The fact that the children have inherited the extra genes and incorporated them into their ‘germline’ means that they will, in turn, be able to pass them on to their own offspring.
Altering the human germline – in effect tinkering with the very make-up of our species – is a technique shunned by the vast majority of the world’s scientists.
Geneticists fear that one day this method could be used to create new races of humans with extra, desired characteristics such as strength or high intelligence.
Writing in the journal Human Reproduction, the researchers, led by fertility pioneer Professor Jacques Cohen, say that this ‘is the first case of human germline genetic modification resulting in normal healthy children’.
Some experts severely criticized the experiments. Lord Winston, of the Hammersmith Hospital in West London, told the BBC yesterday: ‘Regarding the treatment of the infertile, there is no evidence that this technique is worth doing . . . I am very surprised that it was even carried out at this stage. It would certainly not be allowed in Britain.’
John Smeaton, national director of the Society for the Protection of Unborn Children, said: ‘One has tremendous sympathy for couples who suffer infertility problems. But this seems to be a further illustration of the fact that the whole process of in vitro fertilisation as a means of conceiving babies leads to babies being regarded as objects on a production line.
‘It is a further and very worrying step down the wrong road for humanity.’ Professor Cohen and his colleagues diagnosed that the women were infertile because they had defects in tiny structures in their egg cells, called mitochondria.
They took eggs from donors and, using a fine needle, sucked some of the internal material – containing ‘healthy’ mitochondria – and injected it into eggs from the women wanting to conceive.
Because mitochondria contain genes, the babies resulting from the treatment have inherited DNA from both women. These genes can now be passed down the germline along the maternal line.
A spokesman for the Human Fertilization and Embryology Authority (HFEA), which regulates ‘assisted reproduction’ technology in Britain, said that it would not license the technique here because it involved altering the germline.
Jacques Cohen is regarded as a brilliant but controversial scientist who has pushed the boundaries of assisted reproduction technologies.
He developed a technique which allows infertile men to have their own children, by injecting sperm DNA straight into the egg in the lab.
Prior to this, only infertile women were able to conceive using IVF. Last year, Professor Cohen said that his expertise would allow him to clone children –a prospect treated with horror by the mainstream scientific community.
‘It would be an afternoon’s work for one of my students,’ he said, adding that he had been approached by ‘at least three’ individuals wishing to create a cloned child, but had turned down their requests.
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New obesity, height genes found

The University of Western Australia

The researchers discovered four new regions on chromosomes that affect height, and seven related to obesity.  Image: dream designs/Shutterstock Busselton residents and researchers from The University of Western Australia have helped a worldwide scientific collaboration identify new genes associated with height and obesity. The discovery of four new loci (the specific place on a chromosome where a gene is located) affecting height and seven related to obesity is described in a paper published online in Nature Genetics. The paper was authored by more than 300 researchers and is the result of a meta-analysis of dozens of studies around the world collating data from more than 263,000 individuals of European background. UWA contributors included Research Assistant Professor Gemma Cadby of the Centre for Genetic Origins of Health and Disease, who provided analysis of height and weight data from the long-running Busselton Health Study. Dr Cadby said the newly discovered genes represented further pieces in the puzzle as researchers sought to understand the genetic contributions to height and weight. "They already know of some genes likely to affect height and weight, but these genes only explain a limited amount of the contribution of genetics to these traits," Dr Cadby said.  "So a lot of genes still need to be identified, but this is an important step. "The ultimate goal for genetic studies is to further the understanding of human diseases and in doing so, to develop new treatments and ways of preventing disease.  Actually translating the results of studies such as this into providing intervention, management and treatments for people who are obese is a long way ahead, but in order to do those things you need to understand the genetics of the disease.  We have to get this bit of the puzzle before we can move to the next step." Other UWA researchers involved in the paper - Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture - included Clinical Professor Bill Musk, of the School of Medicine and Pharmacology at Sir Charles Gairdner Hospital, and Adjunct Professor John Beilby of the School of Pathology and Laboratory Medicine. The study was put together by the GIANT consortium - Genetic Investigation of Anthropometric Traits.  It focused primarily on BMI (Body Mass Index), which is a major risk factor for multiple chronic diseases and of important public health significance, but also examined height and waist-hip ratio adjusted for BMI. The Busselton Health Study (BHS) is one of the world's longest-running epidemiological research programs.  Since 1966, it has contributed to an understanding of many common diseases and health conditions.  The unique BHS database is compiled and managed by UWA's School of Population Health. Editor's Note: Original news release can be found here.

Scientists find healing 'switch'

Agency for Science, Technology and Research

Illustration of skin tissue. The newly discovered tiny micro-RNA switch controls the migration of skin cells necessary for wounds to close and heal. Image: mopic/Shutterstock Scientists from the Agency for Science, Technology and Research (A*STAR)’s Institute of Medical Biology (IMB) have identified a molecular “switch” that controls the migration of skin cells necessary for wounds to close and heal. This is especially significant for diabetics and other patients who suffer from chronic wounds, wounds that do not heal or take years to do so, which are vulnerable to infections and could lead to amputations. This switch mechanism may hold the key to developing therapeutics that will reduce or prevent chronic wounds. The scientists discovered that a tiny “micro-RNA” molecule, called miR-198, controls several different processes that help wound healing, by keeping them switched off in healthy skin. When skin is wounded, the manufacture of miR-198 quickly stops and the levels of miR-198 drop, switching on many wound healing processes. In the non-healing wounds of diabetics, miR-198 does not disappear and wound healing remains blocked. This therefore identifies miR-198 as a potential diagnostic biomarker for non-healing wounds. These findings were recently published in the prestigious journal Nature. The research leading to this discovery was carried out in collaboration with A*STAR’s Bioinformatics Institute (BII), National University Hospital (NUH), Singapore and Jnana Sanjeevini Diabetes Center, Bangalore, India. Chronic wounds in patients with diabetes are a major global health burden and the most common cause of lower extremity amputations. In Singapore, diabetes is the fifth most common medical condition diagnosed and one in nine people aged 18 to 69 has diabetes. Unfortunately, chronic wounds are currently poorly understood and insufficiently treated.  Chronic wounds also tend to affect the elderly and disabled patients, especially those confined to a wheelchair or bed-bound.  Dr. Prabha Sampath, principal investigator at IMB and lead author of the paper, said, "Moving forward, we hope to translate this research into improved patient outcomes. We can now build on this research, to see how we can modulate the defective switch in chronic wounds by targeting miR-198 and its interacting molecules, to develop new strategies for treating chronic wounds. Our research provides a comprehensive understanding of the mechanism of the wound healing process. Professor Birgitte Lane, Executive Director of IMB, said, “This switch appears to be an entirely new regulatory component in wound healing, and probably a very important one. Poor wound healing is a major healthcare burden, and this discovery is particularly timely in the face of aging populations and the sharp global rise in diabetes. The finding gives us a platform from which to develop therapies that could significantly reduce chronic wounds and improve healthcare." The information necessary to expressmicroRNA-198 (miR-198) and follistatin-like 1 (FSTL1) protein are found in a single “message” produced by the cell. However, miR-198 and FSTL1 protein cannot be produced at the same time – it can only be one or the other. These two molecules also have opposite roles: miR-198 (found in unwounded skin) inhibits skin cell migration and wound healing, whereas FSTL1 protein (expressed after injury) promotes skin cell migration and wound healing. A regulatory switch dictates their expression, and hence controls the “see-saw” between inactive resting skin cells and the cell migration necessary for wound healing. Dr. Sampath and her team showed that healthy unwounded skin contained high levels of miR-198 but no FSTL1 protein. They demonstrated that these high levels of miR-198 prevent skin cell migration by suppressing several genes, such as PLAU, LAMC2 and DIAPH1 [4], which are needed for different aspects of the wound healing process. However upon injury, miR-198 is switched off in the wound by a signal from transforming growth factor β1 (TGF-β1). This allows FSTL1 to now be made instead, and the skin migration genes to be unblocked, promoting migration of skin cells into the wound area to drive skin wound healing. The scientists further examined skin samples of chronic non-healing ulcer wounds from patients with diabetes mellitus. They observed that, unlike healthy skin that had been injured, there remained high levels of miR-198 (inhibiting skin cell migration and wound healing) and an absence of FSTL1 protein (promoting skin cell migration upon wounding), indicating that this “switch” is defective in chronic wounds. Editor's Note: Original news release can be found here.

Cheaper genetic test for diabetes

The University of Western Australia

Using advanced computational methods, the researchers have identified accurate genetic markers that indicate a risk of Type 1 diabetes.  Image: Nikita G. Sidorov/Shutterstock Work by Perth researchers could revolutionise testing for Type 1 diabetes around the world. The research by the Centre for Diabetes Research (CDR) at the Western Australian Institute for Medical research (WAIMR), led by Professor Grant Morahan, has been published in the top journal in the field, Diabetes. Lead author Cao Nguyen, said the new method would make testing much cheaper and quicker to determine what genetic risk factors have for Type 1 diabetes. In this disease, the person's own immune system destroys the cells that make insulin. The strongest genetic risk factors for Type 1 diabetes are the HLA genes known as HLA-DR3 and HLA-DR4. "Currently a blood sample is collected and sent to specialist laboratories where it can cost $300 per sample to test HLA types by the conventional method," Research Assistant Professor Nguyen said. "With this new method, it will cost less than $50 to find a person's HLA risk type. The process will be more affordable and will make it easier for more researchers to investigate type 1 diabetes." Asst. Professor Nguyen tested more than 200,000 genetic markers in the DNA of over 10,000 people as part of the international Type 1 Diabetes Genetics Consortium. Using advanced computational methods, Asst. Professor Nguyen discovered as few as three genetic markers can predict all the HLA risk types that are relevant to Type 1 Diabetes. The overall accuracy of his prediction method was 99.3% - which is more accurate than existing methods. Now that the research has been published, clinicians and researchers across the world can start using the method, providing faster results for people with a family history of Type 1 diabetes. Editor's Note: Original news release can be found here.