Monthly Archives: February 2017

After the 2003 completion of the Human Genome Project which sequenced all 3 billionletters,or base pairs, in the human genome many thought that our DNA would become an open book. But a perplexing problem quickly emerged: although scientists could transcribe the book, they could only interpret a small percentage of it.

The mysterious majority as much as 98 percent of our DNA do not code for proteins. Much of this dark matter genome is thought to be nonfunctional evolutionary leftovers that are just along for the ride. However, hidden among this noncoding DNA are many crucial regulatory elements that control the activity of thousands of genes. What is more, these elements play a major role in diseases such as cancer, heart disease, and autism, and they could hold the key to possible cures.

As part of a major ongoing effort to fully map and annotate the functional sequences of the human genome,including this silent majority, the National Institutes of Health (NIH)on Feb. 2, 2017, announced new grant funding for a nationwide project to set up five characterization centers, including two at UC San Francisco, to study how theseregulatory elements influence gene expression and, consequently, cell behavior.

The projects aim is for scientists to use the latest technology, such as genome editing, to gain insights into human biology that could one day lead to treatments for complex genetic diseases.

After the shortfalls of the Human Genome Project became clear, the Encyclopedia of DNA Elements (ENCODE) Project was launched in September 2003 by the National Human Genome Research Institute (NHGRI). The goal of ENCODE is to find all the functional regions of the human genome, whether they form genes or not.

The Human Genome Project mapped the letters of the human genome, but it didnt tell us anything about the grammar: where the punctuation is, where the starts and ends are.

Elise Feingold, PhD

NIH Program Director

The Human Genome Project mapped the letters of the human genome, but it didnt tell us anything about the grammar: where the punctuation is, where the starts and ends are, said NIH Program Director Elise Feingold, PhD. Thats what ENCODE is trying to do.

The initiative revealed that millions of these noncoding letter sequences perform essential regulatory actions, like turning genes on or off in different types of cells. However, while scientists have established that these regulatory sequences have important functions, they do not know what function each sequence performs, nor do they know which gene each one affects. That is because the sequences are often located far from their target genes in some cases millions of letters away. Whats more, many of the sequences have different effects in different types of cells.

The new grants from NHGRI will allow the five new centers to work to define the functions and gene targets of these regulatory sequences. At UCSF, two of the centers will be based in the labs of Nadav Ahituv, PhD, and Yin Shen, PhD. The other three characterization centers will be housed at Stanford University, Cornell University, and the Lawrence Berkeley National Laboratory. Additional centers will continue to focus on mapping, computational analysis, data analysis and data coordination.

New technology has made identifying the function and targets of regulatory sequences much easier. Scientists can now manipulate cells to obtain more information about their DNA, and, thanks to high-throughput screening, they can do so in large batches, testing thousands of sequences in one experiment instead of one by one.

It used to be extremely difficult to test for function in the noncoding part of the genome, said Ahituv, a professor in the Department of Bioengineering and Therapeutic Sciences. With a gene, its easier to assess the effect because there is a change in the corresponding protein. But with regulatory sequences, you dont know what a change in DNA can lead to, so its hard to predict the functional output.

Ahituv and Shen are both using innovative techniques to study enhancers, which play a fundamental role in gene expression. Every cell in the human body contains the same DNA. What determines whether a cell is a skin cell or a brain cell or a heart cell is which genes are turned on and off. Enhancers are the secret switches that turn on cell-type specific genes.

During a previous phase of ENCODE, Ahituv and collaborator Jay Shendure, PhD, at the University of Washington, developed a technique called lentivirus-based massive parallel reporter assay to identify enhancers. With the new grant, they will use this technology to test for enhancers among 100,000 regulatory sequences previously identified by ENCODE.

Their approach pairs each regulatory sequence with a unique DNA barcode of 15 randomly generated letters. A reporter gene is stuck in between the sequence and the barcode, and the whole package is inserted into a cell. If the regulatory sequence is an enhancer, the reporter gene will turn on and activate the barcode. The DNA barcode will then code for RNA in the cell.

Once the researchers see that the reporter gene is turned on, they can easily sequence the RNA in the cell to see which barcode is activated. They then match the barcode back to its corresponding regulatory sequence, which the scientists now know is an enhancer.

With previous enhancer assays, you had to test each sequence one by one, Ahituv explained. With our approach, we can clone thousands of sequences along with thousands of barcodes and test them all at once.

Shen, an assistant professor in the Department of Neurology and the Institute for Human Genetics, is taking a different approach to characterize the function of regulatory sequences. In collaboration with her former mentor at the Ludwig Institute for Cancer Research and UC San Diego, Bing Ren, PhD, she developed a high-throughput CRISPR-Cas9 screening method to test the function of noncoding sequences. Now, Shen and Ren are using this approach to identify not only which sequences have regulatory functions, but also which genes they affect.

Shen will use CRISPR to edit tens of thousands of regulatory sequences in a large pool of cells and track the effects of the edits on a set of 60 pairs of genes that commonly co-express.

For this work, each cell will be programmed to reflect two fluorescent colors one for each gene when a pair of genes is turned on. If the light in a cell goes out, the scientists will know that its target gene has been affected by one of the CRISPR-based sequence edits. The final step is to sequence each cells DNA to determine which regulatory sequence edit caused the change in gene expression.

By monitoring the colors of co-expressed genes, Shen will reveal the complex relationship between numerous functional sequences and multiple genes, which was beyond the scope of traditional sequencing techniques.

Until the recent development of CRISPR, it was not possible to genetically manipulate non-coding sequences in a large scale, said Shen. Now, CRISPR can be scaled up so that we can screen thousands of regulatory sequences in one experiment. This approach will tell us not only which sequences are functional in a cell, but also which gene they regulate.

By cataloging the functions of thousands of regulatory sequences, Shen and Ahituv hope to develop rules about how to predict and interpret other sequences functions. This would not only help illuminate the rest of the dark matter genome, it could also reveal new treatment targets for complex genetic diseases.

A lot of human diseases have been found to be associated with regulatory sequences, Ahituv said. For example, in genome-wide association studies for common diseases, such as diabetes, cancer and autism, 90 percent of the disease-associated DNA variants are in the noncoding DNA. So its not a gene thats changed, but what regulates it.

As the price for sequencing a persons genome has dropped significantly, there is talk about using precision medicine to cure many serious diseases. However, the hurdle of how to interpret mutations in noncoding DNA remains.

If we can characterize the function and identify the gene targets of these regulatory sequences, we can start to reveal how their mutations contribute to diseases, Shen said. Eventually, we may even be able to treat complex diseases by correcting regulatory mutations.

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The Mysterious 98%: Scientists Look to Shine Light on Our Dark Genome - ScienceBlog.com (blog)

February 23, 2017 Dolphins and humans are very similar creatures. A new database of bottlenose dolphin DNA and associated proteins could possibly aid in dolphin care and research on human medical problems such as stroke and kidney failure. Credit: NOAA

In movies and TV shows, dolphins are often portrayed as heroes who save humans through remarkable feats of strength and tenacity. Now dolphins could save the day for humans in real life, too with the help of emerging technology that can measure thousands of proteins and an improved database full of genetic data.

"Dolphins and humans are very, very similar creatures," said NIST's Ben Neely, a member of the Marine Biochemical Sciences Group and the lead on a new project at the Hollings Marine Laboratory, a research facility in Charleston, South Carolina that includes the National Institute of Standards and Technology (NIST) as one of its partner institutions. "As mammals, we share a number of proteins and our bodies function in many similar ways, even though we are terrestrial and dolphins live in the water all their lives."

Neely and his colleagues have just finished creating a detailed, searchable index of all the proteins found in the bottlenose dolphin genome. A genome is the complete set of genetic material present in an organism. Neely's project is built on years of marine mammal research and aims to provide a new level of bioanalytical measurements. The results of this work will aid wildlife biologists, veterinary professionals and biomedical researchers.

Protein Maps Could Help Dolphins and Humans

Although a detailed map of the bottlenose dolphin (Tursiops truncatus) genome was first compiled in 2008, recent technological breakthroughs enabled the creation of a new, more exhaustive map of all of the proteins produced by the dolphins' DNA.

Neely led the process to generate the new genome with the help of colleagues at the Hollings Marine Laboratory. For this project, the initial genomic sequencing and assembly were completed by Dovetail Genomics , a private U.S.-based company. Next, the genome was annotated by the National Center for Biotechnology Information at the National Library of Medicine (NCBI) using previously deposited data generated in large part by the National Oceanic and Atmospheric Administration's National Centers for Coastal Ocean Science Marine Genomics Core.

"Once you can identify all of the proteins and know their amounts as expressed by the genome," Neely explained, "you can figure out what's going on in the bottlenose dolphin's biological systems in this really detailed manner."

Neely's study is part of an emerging field called proteomics. In the case of dolphins, proteomic work has a wide variety of potential applications.

The zoo and aquarium industry, which generates revenues of approximately $16 billion a year, could use it to improve the care of bottlenose dolphins.

In addition, improved dolphin proteomics could improve assessments of wild dolphin populations, and provide an immense amount of data on environmental contaminants and the safety and health of the world's oceanic food web.

Comparing the proteins of humans and these other mammals is already providing researchers with a wealth of new information about how the human body works. Those findings could eventually be used to develop new, more precise treatment methods for common medical problems.

As marine mammals descend, they shut off the blood flow to many of their organs, which has long puzzled and intrigued biologists. In contrast, if blood stops flowing to the organs of a human's body for even a few seconds, the result can be a stroke, kidney failure, or even death.

Studies have recently revealed that lesser-known proteins in the blood of marine mammals may be playing a big role in the dives by protecting bottlenose dolphins' kidneys and hearts from damage when blood flow and oxygen flow start and stop repeatedly during those underwater forays.

One of these proteins is known as vanin-1. Humans produce vanin-1, but in much smaller amounts. Researchers would like to gather more information on whether or not elevating levels of vanin-1 may offer protection to kidneys.

"There's this gap in the knowledge about genes and the proteins they make. We are missing a huge piece of the puzzle in how these animals do what they do," said Mike Janech from the Medical University of South Carolina. His group has been researching vanin-1 and has identified numerous other potential biomedical applications for the dolphin genome just created by NIST.

"Genes carry the information of life," Janech said. "But proteins execute the functions."

From Macro to Micro

Vanin-1 is just one example of how genomic information about this mammalian cousin might prove useful. There may be hundreds of other similar applications, including some related to the treatment of high blood pressure and diabetes.

This represents another avenue for biomimicry, which seeks solutions to human problems by examining and imitating nature's patterns and strategies. In the past, biomimicry was solely focused on the structural aspects of animal body parts such as arms and legs or functional patterns of things like noses and sniffing. But as the study of DNA has evolved, so too has our ability to examine the things happening at the most minute levels within another mammal's body.

"We are now entering what could be called the post-model-organism era," Neely said. Instead of looking only for a structure to model, imitate or learn from, scientists are looking at the complete molecular landscape of genes and proteins of these creatures for model processes, too. "With abundant genomic resources it is now possible to study non-model organisms with similar molecular machinery in order to tackle difficult biomedical problems."

Data, New Technology and High-Quality Tissue Samples

To gather the needed protein information, Neely and his team used a specimen provided by the National Marine Mammal Tissue Bank (NMMTB), the longest running project of NIST's Marine Environmental Specimen Bank. Half of the approximately 4,000 marine mammal specimens in the NMMTB are collected as a part of the Marine Mammal Health and Stranding Response Program . The specimen provided for Neely's study was known to originate very close to the Hollings Marine Lab.

The new, state-of-the-art genome immediately began providing new biochemical insights. Studies at NIST are ongoing to validate the updated protein maps using an ultra-high-resolution tribrid mass spectrometer, which is the most powerful tool available to identify and quantify proteins.

Other Mammal Proteins Seem Promising, Too

Neely said the results demonstrate the utility of re-mapping genomes with the improved bioanalytical capabilities provided by new genomic sequencing technology coupled to high-resolution mass spectrometers. The data from this project will also be available in the public domain so that the results will be easy for others to access and use for diverse applications and research.

This is the first of many such projects to be undertaken by the Charleston group whereby new analytical techniques could be applied to marine animals. Studying other diving marine mammals can improve our understanding of the molecular mechanisms involved in diving. Also, sea lion proteins may have much to tell us about metastatic cancer, which especially intrigues Neely and his colleagues.

As a research chemist, Neely says he has not really spent much time before now observing marine mammals as a part of his work hours. He does encounter dolphins when he goes out surfing along the Carolina coastline, though.

"It's amazing to think that we are at a point where cutting-edge research in marine mammals can directly advance human biomedical discoveries," he said.

Explore further: Researchers probing the beneficial secrets in dolphins' proteins

Why reinvent the wheel when nature has the answer?

Answers to evolutionary and ecological mysteries about marine mammal species may be closer at hand, thanks to advances in genetic sequencing techniques for so-called nonmodel organisms.

(Phys.org)A team of researchers with members from institutions in Australia, the U.S. and the U.K. has found evidence that suggests increased dolphin familiarity with humans has led to an increase in injury and death to ...

(PhysOrg.com) -- Marine mammal experts have uncovered a new species of dolphin in Australian waters, challenging existing knowledge about bottlenose dolphin classifications and highlighting the country's marine biodiversity.

Bottlenose dolphins in the Florida Coastal Everglades have higher concentrations of mercury than any other populations in the world.

After years of research on dolphin behavior and under pressure from animal rights groups, the National Aquarium in Baltimore has decided to move the marine mammals to a sanctuary, officials said Wednesday.

The last Neanderthal died 40,000 years ago, but much of their genome lives on, in bits and pieces, through modern humans. The impact of Neanderthals' genetic contribution has been uncertain: Do these snippets affect our genome's ...

In the middle of Alberta's boreal forest, a bird eats a wild chokecherry. During his scavenging, the bird is caught and eaten by a fox. The cherry seed, now inside the belly of the bird within the belly of fox, is transported ...

Sexual reproduction and viral infections actually have a lot in common. According to new research, both processes rely on a single protein that enables the seamless fusion of two cells, such as a sperm cell and egg cell, ...

We all do it; we all need ithumans and animals alike. Sleep is an essential behavior shared by nearly all animals and disruption of this process is associated with an array of physiological and behavioral deficits. Although ...

Professor Robert Sinclair at the Okinawa Institute of Science and Technology Graduate University (OIST) and Professor Dennis Bamford and Dr. Janne Ravantti from the University of Helsinki have found new evidence to support ...

A common roundworm widely studied for its developmental biology and neuroscience, also might be one of the most surprising examples of the eat-local movement. Princeton University researchers have found that the organisms ...

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Diving deep into the dolphin genome could benefit human health - Phys.Org

W

hen it comes to cancer, all knowledge is power even when that knowledge is scary. Knowing as much as you can about cancer lets you and your health care team act decisively in devising your treatment strategy. Even more important, it lets you act specifically in selecting treatments or clinical trials that might be best in treating your disease.

Advances in genomics and molecular biology have revealed that cancer is surprisingly, shockingly diverse so much so that we no longer view most cancers as one disease, even those that begin in the same organ or tissue. For example, there are at least 12 subtypes of multiple myeloma, the rare cancer that I have. Each one can be defined by a complex interplay of genetic mutations and other molecular abnormalities, some of which are shared with cancers that originate elsewhere in the body.

For me, learning everything about my disease has been essential to discovering how to attack and treat my cancer and, I believe, why I went into a surprising but welcome long-lasting remission.

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I first had my bone marrow analyzed in 1996, shortly after I was diagnosed with multiple myeloma. The procedure used, fluorescence in situ hybridization (FISH), was the gold standard test at the time to detect certain mutations that might shed light on my prognosis and treatment. It showed I had a type of genetic mutation called t(4;14). It meant that parts of two different chromosomes had switched places.

I will never forget how terrified, how heartbroken I felt when I learned that t(4;14) meant that my already fatal disease was of a particularly aggressive subtype. My remissions would be short, my relapses frequent.

Kathy Giusti: The businesswoman who took on her own cancer

But as I sat with that devastating news, a new drug called Velcade was in development that would change my fate. In spite of, or perhaps because of, our t(4;14) status, individuals like me tend to respond well to Velcade so well that it can help overcome the dismal prognosis conferred by this mutation. Fortunately, with the appropriate treatment, here I am, living life to the fullest 20 years after being diagnosed with a cancer that my doctors thought would kill me in three to four years.

My personal experience reveals just how complex cancer truly is and the powerful role patients can play in contributing to our understanding of cancer. Today, in addition to FISH and other tests like gene expression profiling, a growing number of patients are having their tumors sequenced. This involves comparing your healthy DNA with your cancers DNA. This can pinpoint genetic mutations that give rise to the disease and helps guide treatment of an ever-growing number of cancers.

Some cancer centers already routinely sequence all patients with cancer. Others sequence patients with cancers that arise from well-understood mutations, such as melanoma or colon cancer, for which targeted drug therapies exist.

And it is increasingly common to do gene sequencing for patients with rare cancers, or those whose treatment options have run out, in the hopes that this genetic information can identify a known mutation for which an existing treatment is available often one used for an entirely different form of cancer.

As we sequence and analyze many patient genomes, and learn from that knowledge, we will identify other genetic mutations and abnormalities that give rise to cancer and learn how they affect the treatment path. These predictive insights will benefit not just the individual, but all people with cancer.

Theres no denying that patients may gain knowledge about their cancer that they wish they hadnt. They might find out that their cancer is more aggressive than blood tests or imaging studies had led them and their doctors to believe. They might learn they are at greater risk of certain side effects or complications, or that some drugs just wont work for them.

Still, as someone who has heard both good and bad news about my cancer genome, I would choose knowledge no matter what.

Thats why I urge all patients to have their cancer sequenced. If the technology isnt available, have a sample of tumor tissue banked so it can be sequenced at a later date and, in the meantime, have the tumor analyzed by FISH or gene expression profiling, both of which are very accessible.

But dont stop there. I strongly encourage patients to know the results of this testing. What is my disease sub-type? Am I at high risk? Knowing the answers to these questions may point to potentially lifesaving treatment strategies.

Cancer patients can help build knowledge about this set of diseases by raising our hands for research. My organization, the Multiple Myeloma Research Foundation, conducted the CoMMpass Study. It sequenced the genomes of 1,000 patients with multiple myeloma and then linked that information to patients clinical history what treatments worked for them, what didnt to uncover additional mutations associated with the disease.

CoMMpass unearthed a mutation in whats called the BRAF gene that had never before been linked to myeloma. Most recently it discovered that there are further subtypes within the t(4;14) subtype. One of these appears to confer no worse prognosis than is associated with other subtypes, while another appears to be associated with an extremely fatal form of the disease.

As we continue to build upon our understanding of multiple myeloma, we take our ideas straight to the clinic, where patients can benefit from treatments that are tailored to the unique aspects of their cancer. Based on findings from the CoMMPass study, weve designed and launched clinical trials of drugs that target mutations in BRAF and in p53, a gene often associated with cancer. We also launched a trial specifically for patients with t(4;14) to pinpoint the characteristics genomic and otherwise that contribute to how well a person responds to therapy.

Choose the cancer center thats right for your cancer

This kind of innovation cannot be done alone nor should it. It requires the extensive analysis of a massive amount of patient data. This means that patients who are able to have their genomes sequenced should step up for research and share their data and other health information.

Myeloma patients can do that in our CoMMunity Gateway. There they can share as much or as little about their disease journey as they want, but can also connect with other patients like them and join clinical trials for their subtype as they become available.Other cancer-focused organizations offer similar resources.

To make sense of the data that are swelling into a flood, the global scientific community in clinical medicine, academia, and the biotech and pharmaceutical industries must work as a team. We must also reach across disciplines to create a diverse and powerful brain trust and build partnerships with diagnostic companies, who develop tests to screen for genetic changes, and insurance companies, who see the value in these diagnostics and are willing to pay for them.

While this work might not defeat cancer immediately, it paves the path for future innovation and potentially game-changing therapies.

Kathy Giusti is the founder of the Multiple Myeloma Research Foundation.She is also a senior fellow at Harvard Business School, where she serves as faculty co-chair of the schools Kraft Precision Medicine Accelerator.

Follow Kathy on Twitter @KathyGiusti

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The power and the fear of knowing your cancer genome - STAT

February 22, 2017 Three adult female Tropilaelaps mercedesae infesting the 5th instar honey bee larva. Credit: Dong et. al, Draft genome of the honey bee ectoparasitic mite, Tropilaelaps mercedesae, is shaped by the parasitic life history. GigaScience 2017

Published today in the open-access journal GigaScience is an article that presents the genome of a parasitic mite, Tropilaelaps mercedesae, that infects bee colonies, which are facing wide-spread devastation across the entire world. The research was carried out by an international team of researchers at Jiaotong-Liverpool University and Liverpool University and focused on mites as they are one of the major threats to honey bee colonies. The work revealed that there were specific features in the T. mercedesae mite genome that had been shaped by their interaction with honey bees, and that current mechanisms to control mites are unlikely to be useful for T. mercedesae. The genome sequence and findings provide excellent resources for identifying gene-based mite control strategies and understanding mite biology.

Although there are many potential causes for the decline in honey bee colonies, pathogens and parasites of the honey bee, particularly mites, are considered major threats to honey bee health and honey bee colonies. The bee mite Tropilaelaps mercedesae is honey bee parasite prevalent in most Asian countries, and has a similar impact on bee colonies that the globally present bee mite Varroa destructor has. More, T. mercedesae and V. destructor typically co-exist in Asian bee colonies and with the global trade of honey bees T. mercedesae is likely become established world-wide, as occurred with V. destructor.

Given the ongoing international devastation of bee colonies, the researchers sequenced the genome of T. mercedesae, to assess the interaction between the parasite and host as well as provide a resource for the ongoing battle to save honey bee populations.

The authors identified the genetic components in the genome and compared these to the genome of free-living mites. As opposed to the free-living mites, T. mercedesae has a very specialized life history and habitat that depends strictly on the honey bee inside a stable colony. Thus, comparison of the genome and transcriptome sequences with those of internal and free-living mites revealed the specific features of the T. mercedesae genome and showed that they were shaped by interaction with the honey bee and colony environment.

Of particular interest, the authors found that the mite does not rely on sensing stimulatory chemicals to affect their behavior. The researchers noted that this discovery meant that, "control methods targeted to gustatory, olfactory, and ionotropic receptors are not effective." Instead, control measures will have to use other targets when trying to disrupt chemical communication. The authors further highlighted that, "there will be a need to identify targets for biological control."

The researchers indicated that there were additional difficulties for controlling the mites, saying "We found that T, mercedesae is enriched with detoxifying enzymes and pumps for the toxic xenobiotics and thus the mite quickly acquires miticide resistance. For developing chemical control methods, we need to search for compounds which may not be recognized by the above proteins."

Relevant to this, the researchers investigated the bacteria that infect the bee mite, as little is known about these bacteria. The scientists discovered that the symbiote R. grylli-like bacteria is commonly present in T. mercedesae, and they suggested that "Manipulating symbiotic Rickettsiella grylli-like bacteria, which is associated with T, mercedesae, may also help us to develop novel control strategies."

They further found that this bacteria was involved in horizontal gene transfer of Wolbachia genes into the mite genome. Wolbachia is a bacteria that commonly infects arthropods, but is not present in T. mercedesae. While the authors were not overly surprised at discovering the occurrence of horizontal gene transfer since it has been detected in about 33% of sequenced arthropod genomes, they did note that this "is the first example discovered in mites and ticks as far as we know", and that, since no Wolbachia were currently infecting the mite, this indicated that Wolbachia was once a symbiont for T. mercedesae or its ancestor but it would have been replaced with R. grylli-like bacteria during evolution."

The extent of honey bee colony destruction remains a complex problem, but one that has an extensive impact crop productivity since honey bees are needed for pollination of a variety of plants. Indeed, in several places in China, farm workers have begun to carry out manual pollination to maintain high crop yield in orchards. Thus, research and resources to help combat this global threat are needed now. The findings, genome, transcriptome, and proteome resources from T. mercedesae study add another weapon in the fight to save bee colonies.

Explore further: New insights on how bees battle deadly varroa mite by grooming

More information: GigaScience, DOI: 10.5524/100266

Journal reference: GigaScience

Provided by: GigaScience

In a new study published in the Journal of Apicultural Research, scientists have compared the ability of two strains of honey bees to defend themselves against the parasitic mite varroa by grooming the mites from their bodies.

Researchers in Hawaii and the UK report that the parasitic 'Varroa' mite has caused the Deformed Wing Virus (DWV) to proliferate in honey bee colonies.

An infestation of speck-sized Varroa destructor mites can wipe out an entire colony of honey bees in 2-3 years if left untreated. Pesticides help beekeepers rid their hives of these parasitic arthropods, which feed on the ...

Honey bees are now fighting back aggressively against Varroa mites, thanks to Agricultural Research Service (ARS) efforts to develop bees with a genetic trait that allows them to more easily find the mites and toss them out ...

Parasitic mites Varroa destructor together with the pesticide imidacloprid hamper bees in their search for pollen. The pesticide and the bee parasite reduce the honeybees' flight capacity, causing bee colonies to weaken and ...

A sister species of the Varroa destructor mite is developing the ability to parasitize European honeybees, threatening pollinators already hard pressed by pesticides, nutritional deficiencies and disease, a Purdue University ...

The last Neanderthal died 40,000 years ago, but much of their genome lives on, in bits and pieces, through modern humans. The impact of Neanderthals' genetic contribution has been uncertain: Do these snippets affect our genome's ...

In the middle of Alberta's boreal forest, a bird eats a wild chokecherry. During his scavenging, the bird is caught and eaten by a fox. The cherry seed, now inside the belly of the bird within the belly of fox, is transported ...

Sexual reproduction and viral infections actually have a lot in common. According to new research, both processes rely on a single protein that enables the seamless fusion of two cells, such as a sperm cell and egg cell, ...

We all do it; we all need ithumans and animals alike. Sleep is an essential behavior shared by nearly all animals and disruption of this process is associated with an array of physiological and behavioral deficits. Although ...

Professor Robert Sinclair at the Okinawa Institute of Science and Technology Graduate University (OIST) and Professor Dennis Bamford and Dr. Janne Ravantti from the University of Helsinki have found new evidence to support ...

A common roundworm widely studied for its developmental biology and neuroscience, also might be one of the most surprising examples of the eat-local movement. Princeton University researchers have found that the organisms ...

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Honey bee parasite genome sequenced to aid in fight against bee colony destruction - Phys.Org

Genome studies point to common disease mechanisms in cardiovascular and other diseases Science Daily The human genome has about 3.26 billion building blocks. Searching for variations relevant to the disease therein is like the famous search for a needle in a haystack. In genome-wide association studies (GWAS), researchers focus on typical variations ...

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Genome studies point to common disease mechanisms in cardiovascular and other diseases - Science Daily

The dramatic drop in the cost of genome sequencing, combined with rapidly evolving artificial intelligence, is moving precision medicine into mainstream healthcare.

Sanjay Chikarmane, senior vice president at Illumina, told an briefing at HIMSS17 in Orlando on Monday that the US$100 genome is now in sight.

Illumina is an US company focused on genetics sequencing and analysing big data for biological insights.

The company is also the major partner for the UK Governments 100k Genome project, providing most of the infrastructure through a 78 million partnership with the Genomics England.

During the briefing, Illumina announced a new partnership with Philips. Illumina will use Philips new genomics AI platform to analyse genomics data, identify key mutations and provide the data into clinical workflows.

IBMs Watson Health is also working on the AI genomics initiative with Illumina.

Our mission is to improve human health through sequencing at a massive scale. The first human genome sequenced ten years ago, took years and cost $3 billion, said Chikarmane. We can sequence in less than a day and with our latest instrument it already costs less than $1K. We are now on our way to the $100 genome.

After the briefing, Chikarmane told Digital Health News that he could see the price of DNA sequencing falling below $100 in the future.

We all know the potential is tremendous, barriers of time and cost have been overcome.

But to make it mainstream we have to be able to analyse the data to identify mutations that can be treated, and identify the most effective drugs that can be used to treat patients. And this has to happen in the electronic medical record.

The ability to analyse the tsunami of genomics data generated is now the greatest barrier to progress, he said.

To interpret the vast amounts of genomics data today requires sophisticated, highly trained bioinformatics specialists.

Its the clinical back end and interpretation that is the limiting factor and thats where AI has such potential.

It can currently take 15 hours of a geneticists time to interpret one patient DNA sequence, Chikarmane said.

This is why it has been the realm of academics so far, using very highly trained geneticists, clearly this is not scalable how do you bring it to community hospitals? How do you make mainstream? You have to use AI.

Chikarmane said that genomics has to become embedded in clinical workflows if uptake was to move out of research labs.

To be mainstream genomics has to be at the point of care and with radiology and pathology reports.

Back in England, Genomics sequencing in the NHS has been supported through 100k Genome project. In 2014 the Government announced 300 million funding to support 11 Genome centres, which would be expected to sequence 10,000 genome by 2017.

That target was later pushed back to 2018.

Originally posted here:
Genomics to hit mainstream with AI and $100 genome - Digital Health

Summary

A powerful genome-editing tool called CRISPR allows researchers to precisely modify the DNA of cells. In a first, MSK scientists have now used the technique to build better-functioning CAR T cells for use in cancer immunotherapy. Clinical trials in humans are being planned.

Highlights

Even as experts debate who deserves credit for developing CRISPR, progress using the powerful genome-editing technique is speeding ahead.

The latest advance involves using the technology to build chimeric antigen receptor (CAR) T cells, a type of immunotherapy for cancer. In a new study published today in the journal Nature, Michel Sadelain and colleagues show how CRISPR can be used to create CAR T cells with improved performance packing more punch against tumors in mice.

These CRISPR-engineeredCAR T cells seem to have an optimal level of functioning, says Dr. Sadelain, who directs the Center for Cell Engineering at Memorial Sloan Kettering. They retain their ability to kill tumor cells for much longer than conventional CAR T cells, which tend to burn out more quickly.

CAR T cells have garnered acclaim over the past few years thanks to their stunning success in treating several types of advanced blood cancers, including acute lymphocytic leukemia and chronic lymphocytic leukemia. The approach, which was pioneered at MSK, involves equipping a persons own T cells with special receptors that can find cancer in the body and initiate an immune reaction against it.

These CRISPR-engineeredCAR T cells seem to have an optimal level of functioning.

Michel Sadelain MSK physician-scientist

To date, most CAR T cells are made using a retroviral technology that delivers the CAR gene to the immune cells. This delivery method results in the CAR gene being inserted at random into the genome of the recipient T cells. Because there can be unwanted genetic side effects that result from this somewhat scattershot approach, researchers are interested in developing more-precise delivery methods FedEx for DNA.

In their new paper, Dr. Sadelain and colleagues including two postdoctoral fellows from his lab, Justin Eyquem and Jorge Mansilla-Soto show that they can use a popular version of the CRISPR technology called CRISPR/Cas9 to put the CAR gene right where they want it, producing cellular cancer fighters with improved killing power.

The team initially tested a few different genome addresses before deciding upon a particular region called TRAC, which stands for T cell receptor alpha constant. This region contains the gene for a part of the immune cells main detector of foreign proteins: the T cell receptor for antigen. Using CRISPR, the team was able to slice open the DNA at this location then slip in their new gene the one for the CAR.

CAR T cells made in this fashion have some remarkable properties. Not least, they are more effective at killing human tumor cells in a mouse model of cancer. Dr. Sadelains team found that the improved killing could be traced to the fact that the cells are less likely to become exhausted and so retain the ability to keep on fighting for longer. (Exhaustion is a term immunologists use to describe T cells that express molecules that tamp down their activity. PD-1, a common target of other immunotherapies, is one such molecule.)

The TRAC locus works really well as a genome address, Dr. Sadelain says. You get the most out of your CAR when you express it from this location.

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The cellsimproved performance reflects the placement of the CAR under control of the regulatory machinery that normally governs the immune response to pathogens and cancer. Because of this precise positioning, the cells can turn the CAR on and off in a more natural fashion. In conventional CAR T cells, the CAR is on all the time, which can cause the cells to start out strong but then quickly lose steam.

In a way, theyre tamer cells, Dr. Sadelain says. They dont go wild and thats why they last longer. And, because they last longer, you ultimately need fewer of them, which should make manufacturing easier, he says.

The CAR T approach, which was pioneered at MSK, involves equipping a persons own T cells with special receptors that can find cancer in the body and initiate an immune reaction against it.

A second promising attribute of these cells is the result of what Dr. Sadelain calls the two-in-one strategy: He and his colleagues used CRISPR to both add the CAR to the TRAC locus and, at the same time, interrupt the T cell receptor gene, making assembly of a functional T cell receptor impossible. Knocking out this receptor means that it may be feasible to make CAR T cells using cells from a genetically unrelated donor, without worrying about a serious immune complication called graft-versus-host disease when the donor immune cells attack the recipients normal tissues as foreign.

Even off-the-shelf CAR T cells that could in principle work for anyone are a possibility with this approach, as discussed by Marcela Maus, Director of Cellular Immunotherapy at Massachusetts General Hospital, in an accompanying editorialin Nature.

Though these results are certainly exciting, Dr. Sadelain says the ultimate test of these CRISPRd cells will be when they are infused into human patients. The next step in this line of research will be to conduct a clinical trial to compare the safety and efficacy of CRISPR-built cells with conventional CAR T models. Two such trials, for people with B cell malignancies, are currently being planned at MSK.

The use of CRISPR-modified cells in people would represent a true milestone in biotechnology, one that could serve to prod the entire field of genetic engineering forward. The CAR field is likely to serve as a major testing ground for this emerging genome-editing technology, Dr. Sadelain says.

Originally posted here:
CRISPR Genome-Editing Tool Takes Cancer Immunotherapy to the Next Level - Memorial Sloan Kettering Cancer Center (blog)