Category Archives: Genome

New capabilities for genome-wide engineering of yeast Science Daily "The goal of the work was really to develop a genome-scale engineering tool for yeast . . . traditional metabolic engineering focused on just a few genes and the few existing genome-scale engineering tools are only applicable to bacteria, not ...

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New capabilities for genome-wide engineering of yeast - Science Daily

May 5, 2017 by Jessica Sieff By understanding how species of Daphnia respond to toxic elements like industrial contaminants, toxic algae blooms or thermal stress, scientists can look at how environmental changes caused by agriculture and road runoff or warming temperatures and climate change could impact populations in lakes, rivers and standing bodies of water. Credit: Matt Cashore/University of Notre Dame

For many, experience with Daphnia, commonly known as water fleas, ends in high school. The organism is often used for science experiments exploring water toxicity, because of its sensitivity to environmental factors. But the tiny, transparent microcrustaceans have been studied intensively for more than 150 years, and new research published and featured on the cover of the journal G3 reveals scientists can now take a closer look at its genome.

Researchers have completed a new and improved genome sequence of Daphnia pulex (D. pulex), providing a clearer roadmap of the organism's genome so they can identify the genes and pathways that make this organism so successful in freshwater ecosystems.

Populations of Daphnia, barely visible to the naked eye, can be found in virtually every standing body of water on the planet, including Antarctica. They evolve quickly and are masters of responding to the conditions in their environment. Sensing the chemical cues of nearby predators, some species of Daphnia develop elaborate defensive structures such as spines and helmets that make them harder to eat. While scientists have gained a thorough understanding of what these tiny water fleas do to adapt to varying conditions, they don't yet know how they do it.

"That's why a system like this is so powerful," said Michael E. Pfrender, director of the Genomics & Bioinformatics Core Facility and associate professor in the Department of Biological Sciences and the Environmental Change Initiative at the University of Notre Dame. "We need this genomic infrastructure to add to the ecological context we already have to gain a better understanding of how Daphnia adapt. Because we have an improved genome sequence, we can get a more accurate catalog of genes and when thinking about response to the environment and chemical cues, it's the turning on and off of genes and pathways that's important. The picture is much more complete than it was before."

Calling it the "Portland Arch" genome after the Indiana Nature Preserve where the Daphnia was collected, the new assembly comes six years after the first sequence of D. pulex in 2011. The current study describes how scientists used the latest technology as part of a thorough and methodical process the result of which led to the identification of 18,440 genes.

D. pulex plays a vital role in Earth's ecology. Feeding off of algae and phytoplankton in standing freshwaters, they are the primary grazer in those environments, the "cows of lakes," said Pfrender. They're also primary forage, transferring all of that energy to the fish that eat them. By understanding how species of Daphnia respond to toxic elements like industrial contaminants, toxic algae blooms or thermal stress, scientists can look at how environmental changes caused by agriculture and road runoff or warming temperatures and climate change could impact populations in lakes, rivers and standing bodies of water.

"What happens to this vital part of the ecosystem when conditions change very rapidly? What genes allow some populations to cope with these changes while others fail?" Pfrender said. "That's what we want to find out. This genome sequence provides the toolkit."

Explore further: Study of the evolution of the micro-crustacean group Cladocera

More information: Zhiqiang Ye et al. A New Reference Genome Assembly for the Microcrustacean, G3: Genes|Genomes|Genetics (2017). DOI: 10.1534/g3.116.038638

Scientists of the Senckenberg Institute have studied the evolutionary history of the so-called "water fleas." These tiny crustaceans from the order Cladocera form the basis of the trophic pyramid and therefore play an important ...

Water fleas can thwart their enemies by growing defensive structures such as helmets and spines. What's more, this predator-induced 'arming' process is not a one-size-fits-all approach - they can even tailor their defensive ...

A common species of zooplanktonthe smallest animals in the freshwater food webcan evolve genetic tolerance to moderate levels of road salt in as little as two and a half months, according to new research published online ...

The key to helping animals evolve quickly in response to climate change could actually be their predators, according to a new UBC study.

A University of Michigan biologist combined the techniques of "resurrection ecology" with the study of dated lake sediments to examine evolutionary responses to heavy-metal contamination over the past 75 years.

There are many different kinds of crustaceans, ranging from the shellfish Swedish people eat at traditional crayfish parties every August to tiny relatives found in their millions in both freshwater and saltwater. One of ...

Much is known about flu viruses, but little is understood about how they reproduce inside human host cells, spreading infection. Now, a research team headed by investigators from the Icahn School of Medicine at Mount Sinai ...

For many, experience with Daphnia, commonly known as water fleas, ends in high school. The organism is often used for science experiments exploring water toxicity, because of its sensitivity to environmental factors. But ...

Researchers in dermatology at Lund University in Sweden believe they have cracked the mystery of why we are able to quickly prevent an infection from spreading uncontrollably in the body during wounding. They believe this ...

Vladimir Lukhtanov, entomologist and evolutionary biologist at the Zoological Institute in St. Petersburg, Russia, made a startling discovery: what people had thought was a population of a common species, turned out to be ...

(Phys.org)A team of researchers with the Howard Hughes Medical Institute has found that a ring of cells in the middle of the fruit fly brain acts as a compass, helping the insect understand where it is, where it has been ...

New research helps answer a long-standing mystery of how honeybees sense the size and strength of their colony, a critical cue for the bees to switch from investing solely in survival to also investing in reproduction.

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Scientists reveal new and improved genome sequence of Daphnia pulex - Phys.Org

From a single species of plant comes many teas. The tea tree, a shrub called Camellia sinensis, produces white, green, black and oolong teas. The tea's destiny is a matter of variables.

The final drink reflects the tea cultivar, the growing environment and how the leaves are processed - dried, crushed, steamed, blended. Farmers pluck 'baby' leaves, as one Snapple commercial put it in the mid-2000s, to begin making white tea.

And yet scientists in China, South Korea and the United States say there is another way to further tea's potential, beyond altering the dirt or the stages of harvest or processing.

DNA analysis could lead to "a more diversified set of tea flavours" by tracing the genes responsible for taste, according to Lizhi Gao, a botany professor at the Chinese Academy of Sciences' Kunming Institute of Botany.

He and colleagues have completed the "first high-quality" genome of the tea tree shrub, published this week in the journal Molecular Plant.

The plant took five years to analyse, thanks to the sheer number of DNA sequences involved.

"The tea tree genome is extremely large," Gao wrote in an email to The Washington Post - counting 3 billion base pairs, about four times the size of coffee's genome.

Of hot and invigorating drinks, coffee gets most of the buzz, at least in the United States: this country is home to 140 million daily coffee drinkers and the Starbucks Unicorn Frappuccino, and Americans consume more coffee than people anywhere else.

Researchers sequenced the genome of robusta coffee in 2014, hinting at a future of genetically modified coffees, as The Post reported at the time.

Scientists followed up with the arabica coffee genome in January.

Monday marked the tea tree's turn. It was a long time coming. Dried plants, recently found in a Chinese mausoleum, revealed that emperors in the Han Dynasty enjoyed tea 2,100 years ago, possibly as part of a soup.

The sovereigns were onto something. Today, 3 billion people drink tea, and by one estimate, for every mug of coffee consumed on the planet, humans drink three cups of tea.

Gao and his colleagues had to churn through the tea tree's huge levels of retrotransposons. These repeated DNA sequences, about 80 percent of the tea genome, duplicated themselves into the genome again and again over 50 million years of tea tree evolution.

"It is a mystery why retrotransposon sequences are abundant in this plant but not in another," Gao said.

But the researchers were most interested not in size but in the way tea produces tasty molecules.

"The tea-processing industries in tea-drinking countries, especially in China, have developed numerous tea products with diverse tea flavour," Gao said.

But processing techniques alone aren't enough, he said. Tea also depends on developing new plant varieties, containing unique combinations of flavourful molecules.

Three types of chemicals are most responsible for tea's taste. One is an amino acid only found in tea, called l-theanine, which in the last decade has been added to drinks that promote focus and concentration. (Such focus drinks are of dubious efficacy and lack supporting research.)

The second type of chemical is a class of flavonoid, or plant pigment molecule, called catechins. The third is caffeine, which evolved in tea independently of cacao and coffee, akin to the way both sea turtles and dolphins evolved flippers separately.

There are several theories as to why plants produce caffeine. Caffeine at high doses is a natural pesticide. But at low doses, as in some nectars, it may be giving insects a memorable jolt.

Caffeine was one tool in tea's repertoire of "disease defense and environmental stress tolerance" methods to help it adapt globally to diverse habitats, Gao said.

The tea genome answered a question the scientist had long pondered: Why can't we make tea from close Camelliasinensis cousins, such as the tea oil plant Camellia oleifera?

It turns out that C. oleifera and its 100 other Camellia relatives do not produce high amounts of the caffeine or catechin family of genes. (Caffeine and catechins are not proteins but secondary metabolites, which means many genes are required to construct them.)

Put another way, Gao said, the expression levels of caffeine- and catechin-related genes "determines the tea processing suitability".

The chief horticulturist at Britain's Royal Horticultural Society, Guy Barter, said plant breeders would welcome this work.

"Once you understand the basis for the flavours and the processing quality of the tea, you can then have genetic markers that breeders can look for when trying to produce new varieties," he told the BBC.

2017 Washington Post

This article was originally published by The Washington Post.

Excerpt from:
The Tea Plant's Genome Has Been Unlocked - And It's 4 Times That of Coffee - ScienceAlert

Indian company to collect genomic code of 1 lakh Asians, including over 30,000 Indians from various parts of the country

Hyderabad: Imagine a repository of over 30,000 Indian genomes covering a wide variety of groups from various regions and ethnic backgrounds accessible to researchers and healthcare providers.

Such a large Indian genomic data will not only enable researchers in finding the patterns of how genes are expressed but also can help in spotting mutations, which could be the answer for personalized therapy protocols for cancer patients, cardio-vascular ailments, end-stage kidney ailments and many more.

An Indian company along with several others in Asia has taken up this amibtious project to collect the genomic code of a whopping 1 lakh Asians, which also includes over 30,000 Indians from various parts of the country.

In the past, there have been isolated attempts at finding genomic sequence of one or two Indian groups but this is for the first time that a concerted effort is being taken up to collect the genome sequence of such a large set of population.

Standard genome Indian researchers need to have access to standard Indian genomic data to isolate the genes responsible for causing ailments among Indians. Almost all the medical standards, for instance ideal BP levels, sugar levels or anything else is based on Caucasian population. In the coming years, we intend to sequence genome of Indians and hopefully reach towards a standardized Indian genome, says CEO (India), MedGenome, Girish Mehta.

Talking to Telangana Today, Mehta said that MedGenome, a Bengaluru-based company, has already committed US$ 10 million for the project. The overall cost of the 1 lakh Asian genome is close to Rs. 100 crore or over 120 million US dollars.

We are collaborating with Singapore and South East Asian biotech companies to take part in preparing this genomic sequence. This will be very important because we will not only get to know the standard Indian genome but also the Asian genomic sequence, which is vital to form new treatment protocols, Mehta said, during a visit to Hyderabad.

Back in 2014, the United Kingdom had launched its own 1 lakh genome project and similar projects are under way in Qatar, Europe and the US.

Unfortunately, we are second largest population but we still do not have our own standard genome code. Earlier, genome sequencing of a single human being was very expensive but technology is rapidly making it very affordable. This is a four-year project and hopefully it should be completed in time, Mehta added.

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Towards India's own standard genome sequence - Telangana Today

Improved plant and animal strains bred with the use of genome editing do not fall within the scope of EU legislation on genetically modified organisms (GMOs) and should be regulated according to the specific agricultural trait or product, rather than the technology by which they are produced, according to a report by the European Academies' Science Advisory Council (EASAC), a body representing all the EUs national academics.

EASACs recommendations are intended to provide a road map for policy makers as genome editing techniques become cheaper and more advanced. A European Commission decision on the status of these products is urgent in view of the accelerating pace of research and development and of the regulatory initiatives being undertaken by individual member states, the report says.

Germ line (heritable) genome editing of human embryos that are intended for use in establishing a pregnancy should not be allowed, but the report backs the use of the technique in basic research, saying, It should proceed subject to appropriate legal and ethical rules and standardised practices.

The report suggests the Commission should, nonetheless, take note of what is being discussed and proposed outside the EU, pointing to the report by the US National Academy of Sciences published in February, which recommended the door should not be closed on the use of germ line genome editing for treating serious disease or disabilities.

The EASAC report comes at a time when scientists are making spectacular progress in genome editing and policy makers in several member states are starting to lay the regulatory ground.

For example, a gene edited canola strain has been assessed as being non-GMO in Germany. The Swedish Board of Agriculture also confirmed that some plants in which the genome had been edited using CRISPRCas9 do not fall under the EU GMO definition.

Genome edited plants have received a green light from the US Government too, including CRISPRCas9-edited mushrooms, in which the activity of a particular enzyme is reduced, extending the shelf life, and a strain of corn engineered to generate a certain kind of starch.

The first phase I CRISPRCas9 clinical trial has started in China, enrolling patients suffering from lung cancer.

Against this backdrop, the report says it would seem reasonable to conclude that there is a case for considering genome editing in livestock breeding.

Examples of the potential benefits include making chickens resistant to infectious diseases and modifying them to produce only female offspring, avoiding the culling of male chicks, which are not required for egg production.

Bees, one of the most important insects for crop production, could be modified to be less susceptible to mites, fungi or other pathogens. The Belgian Blue, a breed of cattle, has suffered problems related to significant inbreeding with which gene editing may help.

EU paralysed on GMOs

The EU regulation of genome editing in plants and animals will be subject to a forthcoming decision of Directorate General for Health and Food Safety, DG Sante, on what is a GMO.

For now, the area of science is in a state of legal limbo. Current EU legislative frameworks governing the genetic modification of plants and animals are controversial. Even where there is an overarching EU policy framework, there is little certainty for researchers and breeders, because individual member states vary in their implementation or can exercise an opt-out.

In some member states there is considerable uncertainty about whether existing bans on genetic engineering in embryos and germ line cells for clinical applications also prohibit basic research.

The regulation of genetic engineering techniques in Europe is a legacy of contention and polarisation, the report says. This echoes a report by the UK House of Commons Science and Technology Committee on genome editing published last year, which said, The regulation of genetic science is an area in which the EU has so far not come close to satisfactorily demonstrating an evidence-based approach to policy making.

Despite continued uncertainty over the rules, some European countries are streaking ahead on gene-editing. Basic research in human embryos of up to 14 days, under licence, is now approved in the UK and Sweden.

To avoid adding to the legal morass, the report calls for more social sciences research. Genome editing raises fears of a slippery slope thatleads to a society of genetic haves and have-nots. There may be a risk of increasing inequality and tension between those who have access to the benefits of genome editing applications and those who do not, the report says.

While concerns have been raised about the possibility of genome editing being practised outside regulated laboratory settings the report is relaxed about DIY biohackers playing around with genome editing tools.

The equipment and reagents are readily available but, There is no evidence that genome editing is much used yet by DIY biologists, the report says. There is no reason to expect the DIY community to cause more harm when using genome editing than anyone else, and DIY biologists must similarly conform to established biosafety legislation.

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Genome editing of plants and livestock needs new approach to regulation - Science Business

smithsonian.com May 3, 2017

There are lots of different kinds of teablack tea, green tea, white tea, oolong and more. Like coffee and wine, the flavor of tea is shapedby the soil in which tea plants aregrown, the variety of the bush, as well as how it is dried and processed. But the biggest factor is something researchers have not had access to until now: the genome of Camellia sinensis.

This species produces almost all of the world's tea (except for herbal,rooibos tea and that fruit-flavored stuff). AsBen Guarino at the Washington Post reports, researchers from the Kunming Institute of Botany in China recently published the first draft of teas genome in the journal Molecular Plant, which will allow scientists to begin reading the tea leaves about, well,tea.

According to a press release, the genome has confirmed some things researchers already suspected. For instance, they believed much of teas flavor comes from a flavonoid called catechin. And while all the plants in the genus Camellia can produce catechinandcaffeine, the species commonly used for tea (sinensis)expresses those particular genes at a much higher levels. Thismeans itsleaves containmore catechin and caffeine, makingit the only species suitable for producing tea.

There were some surprises, too. For instance, the genome has over 3 billion pairs, making it four times the size ofthe coffee genome. That's likely because the sequence is full of what's known as jumping genes, which can copy themselves and then insert into the genome multiple times. All of that repetition made sorting out the sequence extra difficult. In fact, it took over fiveyears to piece ittogether.

Our lab has successfully sequenced and assembled more than twenty plant genomes, Lizhi Gao, plant geneticist and an author of the study, says in the press release. But this genome, the tea tree genome, was tough.

Now that the first draft is finished, Gao says the team will begin double-checking the work and also examine different varieties of tea from around the world to figure out how genes affect flavor. Even as the work continues, the new road map could help cultivators figure out how to breed new tea plants.

The results of the study could not only impact the breeding of tea, but also breeding of other plants used medicinally or in cosmetics, Monique Simmonds, deputy director of science at Kew Royal Botanic Gardens in the UK, tellsHelen Briggs at the BBC. [T]he compounds that occur in tea are often associated with the biological properties of plants used medicinally or in cosmetics, she says.

This is just the latest in stimulating beverage research. In 2014 researchers published the genome of robusta coffee, which makes up about 30 percent of the world coffee market. Andin January, scientists publishedthe genome of Arabica coffee, which makes up the other 70 percent of the market.

One of the big hurdles all of these beverages face is climate change, which could impact tea growing regions and is already impacting the flavor of some teas. Coffee, which grows best in certain microclimates, is facing similar pressures. It's possible that using the new genomes breeders and scientists can produce plants that are able to withstand changing climates, temperatures and emerging diseases.

Let's hope that's the case. The quali-tea of our daily caffeine sources depend on it.

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Researchers Read the Genome in the Tea Leaves | Smart News ... - Smithsonian

A team in China has decoded the genetic building blocks of the tea plant, Camellia sinensis, whose leaves are used for all types of tea, including black, green and oolong.

Until now, little has been known about the genetics of the plant, despite its huge economic and cultural importance.

The researchers found that the leaves of the tea plant contain high levels of chemicals that give tea its distinctive flavour. They include flavonoids and caffeine.

Overall, the findings from this study could have a significant impact on those involved in the breeding of tea but also those involved in breeding many plants used medicinally and in cosmetics, as the compounds that occur in tea are often associated with the biological properties of plants used medicinally or in cosmetics, [said Dr Monique Simmonds, deputy director of science at Kew Royal Botanic Gardens.]

Decoding the genome of the tea plant took more than five years. At three billion DNA base pairs in length, the tea plant genome is more than four times the size of the coffee plant genome and much larger than most sequenced plant species.

[Read the full study here.]

The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion, and analysis. Read full, original post:Secrets of tea plant revealed by science

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Read the tea leaves: Decoded plant genome unlocks flavor secrets ... - Genetic Literacy Project

At a recent conference promoting harmony between science and biblical faith, a New Testament professor at an American Baptist seminary said genetic evidence suggesting that humans descend not from an individual pair but from a large population changed the way he interprets the first three chapters of Genesis.

Scot McKnight, a professor at Northern Seminary in Lombard, Ill., who writes the popular blog Jesus Creed, said at the 2017 BioLogos conference on Christ and creation in Houston that in years of teaching introduction to the Bible to undergraduate students he typically encountered one of two responses.

Scott McKnight

My conservative students were frightened by the prospect of the Bible being wrong, and so they were afraid of evolution, better to keep it suppressed, McKnight said in a conference address video posted on YouTube. You could call it whatever kind of evolution you wanted theistic or creationary evolution or evolutionary creationism or just plain old Darwinian evolution its the term evolution that created the problem.

The other students were science students, who as those conservative students were worrying about evolution, these students were worrying about the Bible and its truthfulness, he said. For them if they were to hear yet again that belief in evolution was dangerous or that the Bible teaches six-day creationism or that the earth was only a few decades or thousands of years old, they would no longer be able to trust the Bible.

McKnight, who grew up Baptist but in 2014 was ordained as an Anglican deacon, said Adam and the Genome, his recent book co-authored with evangelical geneticist Dennis Venema, is geared toward the student who believes in both evolution and the Bible and wants to avoid a crisis of conscience resulting from conflict between the two.

McKnight, a recognized authority on the New Testament, early Christianity and the historical Jesus, said the stakes for such students are high.

The number one reason young people walk away from the faith is the conflict of their interpretation of Scripture with their interpretation of science, he said. Let it be emphasized that we are dealing here with the interpretation of Scripture, not necessarily Scriptures truest meaning. And, yes, we are dealing with a theoretical construct called evolution.

McKnight said many people on both sides regard science and faith as implacable enemies.

Some scientists think we are fools for believing in the Bible and therefore in Jesus, he said, while for some conservative theologians and pastors and bloggers, scientists are materialists, atheists, and those who think they are Christian and evolutionist are oblivious to the slippery slide they are halfway down.

McKnight said the question he hears most often when discussing Gen. 1-3 is do you believe in a historical Adam? Its a question loaded with theological meaning, he said, including belief that Adam and Eve were real people who had a biological and procreative relationship with every human being who has ever lived and that all people living today possess a share of their DNA.

Since that inheritance includes sin, death and the universal need for redemption, McKnight said, the gospel is at stake in the argument.

Unless I am mistaken, there never was only two solitary human beings on planet Earth from whom we have descended and from whom we get our DNA, he said.

McKnight draws from church history to explain the discrepancy. St. Augustine said when natural scientists are able from reliable evidence to prove some fact of physical science we shall show that it is not contrary to Scripture, he said.

I begin with the assumption that the Bible is truthful and right, and not wrong, McKnight said. Some call this inerrancy. I like to call it truthfulness.

The professor said as he became familiar with findings of the Human Genome Project he was drawn to writers who interpret the first chapters of Genesis as an ancient Near Eastern creation narrative instead of as literal history.

McKnight, author of more than 50 books, said even he struggles with describing the specific genre. When I read a text that names a male Dusty or Clay or Earth Man and a female fashioned from the side of a rib of Dusty named Mama of All Living Humans, and when I read of a serpent that talks and actually fools people made in Gods image, I do have to ask questions about genre, he said.

McKnight said he doesnt like the terms myth, fable and legend when applied to Genesis, so he uses theological narrative.

I read the text as a theological narrative about God as creator, about humans assigned by God to a vocation in Gods cosmic temple on Gods sacred time, and I see the tragedy of humans who refuse to do what God said, he said.

The BioLogos Foundation, founded in 2007 by Francis Collins, the scientist who directed the Human Genome Project and in his personal life moved from atheism to Christian belief, presents an evolutionary understanding of Gods creation while seeking gracious dialogue with those who disagree.

Northern Seminary, founded in 1913, is affiliated with American Baptist Churches USA. The current president, Bill Shiell, is a graduate of George W. Truett Theological Seminary and former pastor of Cooperative Baptist Fellowship churches including First Baptist Church in Tallahassee, Fla.; First Baptist Church in Knoxville, Tenn.; and Southland Baptist Church in San Angelo, Texas.

The seminary recently announced plans to move from theLombard location in Chicagos western suburbs to a new center in nearby Lisle, establish an additional new center on Chicagos South Side, offer new programs at its existing Lawndale center on Chicagos West Side and expand online learning.

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Professor says Human Genome Project changed his reading of Gen. 1-3 - Baptist News Global

I like the line on p. 140 from Durhams own Venerable Bede Adam had the burden of embarrassment, but not the humility of confession. Scots next comment is near the mark on the same page Every conceivable relationship is affected by their choice, and this infection begins to spread until in 8.21 God can say this of human every inclination of the human heart is evil from childhood.

I agree with the view that the banishment from the garden is to prevent Adam and Eve from eating from the tree of life and becoming everlasting fallen creatures on earth. In other words, I think Adam and Eve were created mortal, just as Jesus himself. Physical Mortality is a natural trait of all creatures before the Fall. Were death simply a product of sin, including the original sins, it would be rather difficult to explain how death on a cross didnt entail Jesus being a sinner. No, the natural limitations of all humans are limitations of time, space, knowledge, power and mortality, none of which are inherently a result of sin. Jesus was like us in all respects, including mortality, save without sin. He had no fallen human nature, and yet he was mortal.

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Adam and the Genome Part Eighteen - Patheos (blog)

May 4, 2017 Corresponding author Michael Dyer, Ph.D., a Howard Hughes Medical Institute Investigator and St. Jude Department of Developmental Neurobiology chair. Credit: St. Jude Children's Research Hospital

A team from the St. Jude Children's Research Hospital Washington University Pediatric Cancer Genome Project (PCGP) has mapped the intricate changes in the "epigenetic" organization of the nucleus to determine how retinal cells transition from immature cells to mature retinal neurons. The researchers have also mapped the epigenome of retinoblastoma cells as they turn cancerous.

The data are an invaluable resource for discovering the still-unknown cellular origin of retinoblastomathe most common eye cancer in children. Scientists can also explore the data for pathways that trigger adult retinal diseases like age-related macular degeneration and retinitis pigmentosa.

The researchers were led by Michael Dyer, Ph.D., a Howard Hughes Medical Institute Investigator and St. Jude Department of Developmental Neurobiology chair. The work appears in the May 3 issue of the journal Neuron.

Epigenetic controls are molecular switches that turn genes on or off to orchestrate a cell's development from a generic cell to a specialized cell like a neuron. While the "genome" of thousands of individual genes is like data stored on a computer disk, the "epigenome" is like a computer program that controls how stored data are read.

Researchers know that epigenetic malfunctions can drive cancers and degenerative diseases, but they have not cracked the "epigenetic code"the specific changes in the organization of the nucleus that guide each type of cell to differentiate from a progenitor cell to a specialized cell.

The researchers used tools of epigenomic analysis to trace the specific epigenetic switches controlling each of thousands of genes in both mouse and human retinal cells as the cells progressed through development.

Analyzing the data revealed surprises about the epigenetic processes of retinal neuron development, Dyer said. One such surprise was the relative importance of two types of epigenetic control switches for retinal development. One control is DNA methylation, which is a chemical alteration of a gene that switches it on or off. The other control switch is histone modification. Histones are proteins that serve as a scaffold for coiling up the DNA into the tight space of the nucleus.

"The perception of the research community was that DNA methylation was the major epigenetic controller," Dyer said. "But to our surprise, only a small percentage of the changes in gene expression during development had any correlation with DNA methylation. It's at the histone level that we saw the really profound changes during differentiation."

Another unexpected discovery, Dyer said, was the point during development when the immature cells transition from making new tissue by dividing rapidly, to differentiating into a mature retinal neuron.

"It's like flipping a giant switch," Dyer said. "Early in development, all the cells are immature progenitors that are rapidly growing and dividing. Then, when those cells stop growing and start becoming neurons, there was a dramatic shift in the epigenome.

"We thought cells would actively shut down those progenitor growth genes, because it would not want them to reactivate and lead to a tumor," he said. "But instead, many of those genes just went from a very active state into what we call an 'empty' state. The cell didn't make any particular effort to shut them down. On the flip side, those genes needed for differentiation, which were repressed in the progenitor cells, had their epigenetic repression removed."

Mapping the epigenetic changes in developing retinoblastoma mouse and human cells yielded similar important insights, Dyer said. "We still don't know which type of cell gives rise to retinoblastoma," he said. "The tumor cells have a mixed program of progenitor cells and neurons. It appears as though they are stuck at the stage when the epigenetic switch is normally flipped to transition from progenitors to neurons.

"While this study can't answer the origin question, it did narrow down the developmental window when the normal cell becomes a tumor cell," he said. "I would have guessed that it would be very early, when a progenitor was rapidly dividing. But we found that the decision point was during a period when the cells were transitioning from rapid growth to differentiation. This insight will allow us to focus on that stage to better understand how retinoblastomas originate."

Added Robert Fulton, director of technology development at Washington University's McDonnell Genome Institute, which contributed to the sequencing and analysis of the data: "This research is a great example of the value of comprehensive genomic analyses and the insights that can be gainedfrom thorough, well-designed studies. To really understand theorigins of retinoblastoma, we need to look beyond genes to understand how epigenetic changes drive cancer."

The new epigenomic data will also enable scientists to search for epigenetic abnormalities underlying adult retinal disease, Dyer said.

"There are some patients with retinal disease who don't show gene mutations that we know are responsible for disease," he said. "Instead, those people might have mutations in epigenetic controls called 'enhancers.' We've provided the first map of these enhancers in the retina, so researchers can discover such mutations."

Dyer and his colleagues also mapped the three-dimensional organization of the retinal epigenome to discover how retinal cells package their genes in concentric regions of the cell nucleus. The organization makes some genes more available than others to be turned on and off.

"It's like packing a suitcase for a trip," he said. "You put the clothes you need in a suitcase to take with you; but those you don't need, you leave in the closet. In our studies, we're trying to decipher the functional significance of why the retinal cell packs some genes away and makes others more accessible.

"All our data will serve as a key resource for investigators exploring specific questions about retinal development and disease," Dyer said. To make the data readily available to other researchers, he has uploaded it to ProteinPaint, a St. Jude web portal that gives scientists worldwide access to masses of cancer genomic data.

Explore further: New measurements reveal differences between stem cells for treating retinal degeneration

More information: Issam Aldiri et al. The Dynamic Epigenetic Landscape of the Retina During Development, Reprogramming, and Tumorigenesis, Neuron (2017). DOI: 10.1016/j.neuron.2017.04.022

By growing two types of stem cells in a "3-D culture" and measuring their ability to produce retinal cells, a team lead by St. Jude Children's Research Hospital researchers has found one cell type to be better at producing ...

Scientists have uncovered how tumor cells in aggressive uterine cancer can switch disguises and spread so quickly to other parts of the body. In a study published in Neoplasia, researchers at the Washington University School ...

In a new study, researchers at Uppsala University have found evidence of a new principle for how epigenetic changes can occur. The principle is based on an enzyme, tryptase, that has epigenetic effects that cause cells to ...

A review article by researchers at Boston University School of Medicine (BUSM) suggests that epigenetics may be a useful target to stop the growth, spread and relapse of cancer. The findings are published online in Volume ...

A newborn's brain is abuzz with activity. Day and night, it's processing signals from all over the body, from recognizing the wriggles of the child's own fingers and toes to the sound of mommy's or daddy's voice.

Neuroscientists at Tufts University School of Medicine have discovered a new signaling pathway that directly connects two major receptors in the brain associated with learning and memorythe N-methyl-D-aspartate receptor ...

Working with mouse, fly and human cells and tissue, Johns Hopkins researchers report new evidence that disruptions in the movement of cellular materials in and out of a cell's control centerthe nucleusappear to be a ...

A team from the St. Jude Children's Research Hospital Washington University Pediatric Cancer Genome Project (PCGP) has mapped the intricate changes in the "epigenetic" organization of the nucleus to determine how retinal ...

Long assumed to be a mere "relay," an often-overlooked egg-like structure in the middle of the brain also turns out to play a pivotal role in tuning-up thinking circuity. A trio of studies in mice funded by the National Institutes ...

One day, our brains will not work the way they used to, we won't be as "sharp" as we once were, we won't be able to remember things as easily.

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Team maps genome organization to link retinal development and retinoblastoma - Medical Xpress