Which genetic changes predispose to disease? How do characters in a novel relate to each other? Which wine and cheese go well together?

Turns out, theres an app for that and its about to become far more versatile as University of Toronto researchers work to release it to a wider community with the support of the Chan Zuckerberg Initiative.

CalledCytoscape, the software in question is already an essential tool for viewing networks in biology, including gene networks that hold clues about how different genes co-operate to sustain health and how these networks change in disease. But like most research software, its currently a desktop application that has to be installed and updated, and doesnt work on phones or tablets.

Today, the Chan Zuckerberg Initiative announced it is providingU of TsGary BaderandHannesRst, both researchers at the Donnelly Centre for Cellular and Biomolecular Research, with US$150,000 each to create a cloud-based Cytoscape and Open MS.Co-founded by Facebook chief executive Mark Zuckerberg and his spouse, Priscilla Chan, the initiative seeks to harness technology to accelerate progress in science.

The future of data analytics should be that it is easier to do, easier to share information and it should be easier for people to collaborate, says Bader, a professor of computational biology who is cross-appointed to the department of molecular genetics in the Faculty of Medicine and the department of computer science in the Faculty of Arts & Science, andholds the Ontario Research Chair in Biomarkers of Disease.

Just as web-based cloud computing has transformed how we listen to music and store data, Bader, whose team is developing the web-based Cytoscape Explorer, says that freedom fromhaving to keep track of files and e-mail them back and forth will boost creativity and speed up science.

Because your document lives on the cloud, the latest version is already there, and you can access it anytime, anywhere. It makes it easier to see what everyone else is doing and youre exposed to more ideas that changes the way you do things in a positive way.

Initially designed for genomics researchers, Cytoscape incorporates the basic principles of network theory and can be easily adapted for other applications. Besides biology, it has been used in business, social studies and marketing, as well as mapping how characters in an epic science fiction novel relate to each other.

We are building the foundation for other people to do research,saysHannesRst,an assistant professor of computational biology at the Donnelly Centre(photo by Jovana Drinjakovic)

Bader even adapted the softwareto find optimal wine and cheese combinations for a dinner party.

Research analytics have been slow to move to the cloud because it is difficult to obtain funding purely for software development unless it promises to reveal new insights. Yet cloud analytics are desperately needed to support increasingly collaborative research often involving teams scattered around the world.

We are building the foundation for other people to do research, says Rst, an assistant professor of computational biology who is also cross-appointed to the departments of molecular genetics and computerscience, and whose team is developingOpenMS, a free tool for biomarker analysis.

With more than one million downloads since launching in 2001, Cytoscapes popularity is only likely to grow with the move to the cloud.

We really think that making this available on the web will allow users who never previously discovered the software, and never used it on the desktop, to easily access it, says Bader, who joined the Cytoscape team in the early 2000s and is leading the newly funded project with Dexter Pratt, a software engineer in the group of Trey Ideker, a professor at the University of California, San Diego, and a co-founder of Cytoscape.

If scientists knew what healthy looked like at the molecular level, they might be able to spot disease as it begins to develop and potentially halt it.

Molecular profiling of human tissue blood, for example produces vast amounts of complex data calling for sophisticated analysis tools such as OpenMS, a leading free software for the analysis of data produced by mass spectrometry, which identifies and counts molecules based on their unique mass-to-charge ratio.

Composed of a set of algorithms that can be rearranged into different workflows, Open MS can be tailored to individual user data. Butin its current form, it requires a certain level of coding knowledge, discouraging uptake among users without programming experience.

The cloud version will have no such obstacles.

We want to make OpenMS user-friendly, using a graphic user interface where users can click on buttons to start their analysis instead of typing commands on the command line, says Rst, who holds the Canada Research Chair in Mass Spectrometry-based Personalized Medicine.

Programming-savvy users will be able to inspect and modify the source code to their needs.

To set up OpenMS on the cloud, Rst will take advantage of so-called Docker containers, which are sets of code that enable standardized software packaging so that it runs the same way on any platform.

The software will be hosted on Niagara, a supercomputer cluster at U of T and part of ComputeCanada, the high-performance computing infrastructure established by the federal government.

The overarching goal of Rsts research is to identify early biomarkers of diabetes and cancer.

We want to take peoplesbody fluids and generate a metabolic profile that we can track over time how people change, he says.

His team recently acquired a state-of-the-art mass spectrometry instrument worth $1 million, with support from the Canada Foundation for Innovation and U of Ts Faculty of Medicine. The instrument, referred to among lab members as the space ship for its futuristic look, can detect trace amounts of biomolecules for more accurate profiling.

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With the help of Chan Zuckerberg Initiative, U of T researchers develop data tools to accelerate science - News@UofT

Genome editing (also called gene editing) is a group of technologies that give scientists the ability to change an organism's DNA. These technologies allow genetic material to be added, removed, or altered at particular locations in the genome. Several approaches to genome editing have been developed. A recent one is known as CRISPR-Cas9, which is short for clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9. The CRISPR-Cas9 system has generated a lot of excitement in the scientific community because it is faster, cheaper, more accurate, and more efficient than other existing genome editing methods.

CRISPR-Cas9 was adapted from a naturally occurring genome editing system in bacteria. The bacteria capture snippets of DNA from invading viruses and use them to create DNA segments known as CRISPR arrays. The CRISPR arrays allow the bacteria to "remember" the viruses (or closely related ones). If the viruses attack again, the bacteria produce RNA segments from the CRISPR arrays to target the viruses' DNA. The bacteria then use Cas9 or a similar enzyme to cut the DNA apart, which disables the virus.

The CRISPR-Cas9 system works similarly in the lab. Researchers create a small piece of RNA with a short"guide" sequence that attaches (binds) to a specific target sequence of DNA in a genome. The RNA also binds to the Cas9 enzyme. As in bacteria, the modified RNA is used to recognize the DNA sequence, and the Cas9 enzyme cuts the DNA at the targeted location. Although Cas9 is the enzyme that is used most often, other enzymes (for example Cpf1) can also be used. Once the DNA is cut, researchers use the cell's own DNA repair machinery to add or delete pieces of genetic material, or to make changes to the DNA by replacing an existing segment with a customized DNA sequence.

Genome editing is of great interest in the prevention and treatment of human diseases. Currently, most research on genome editing is done to understand diseases using cells and animal models. Scientists are still working to determine whether this approach is safe and effective for use in people. It is being explored in research on a wide variety of diseases, including single-gene disorders such as cystic fibrosis, hemophilia, and sickle cell disease. It also holds promise for the treatment and prevention of more complex diseases, such as cancer, heart disease, mental illness, and human immunodeficiency virus (HIV) infection.

Ethical concerns arise when genome editing, using technologies such as CRISPR-Cas9, is used to alter human genomes. Most of the changes introduced with genome editing are limited to somatic cells, which are cells other than egg and sperm cells. These changes affect only certain tissues and are not passed from one generation to the next. However, changes made to genes in egg or sperm cells (germline cells) or in the genes of an embryo could be passed to future generations. Germline cell and embryo genome editing bring up a number of ethical challenges, including whether it would be permissible to use this technology to enhance normal human traits (such as height or intelligence). Based on concerns about ethics and safety, germline cell and embryo genome editing are currently illegal in many countries.

Gupta RM, Musunuru K. Expanding the genetic editing tool kit: ZFNs, TALENs, and CRISPR-Cas9. J Clin Invest. 2014 Oct;124(10):4154-61. doi: 10.1172/JCI72992. Epub 2014 Oct 1. Review. PubMed: 25271723. Free full-text available from PubMed Central: PMC4191047.

Hsu PD, Lander ES, Zhang F. Development and applications of CRISPR-Cas9 for genome engineering. Cell. 2014 Jun 5;157(6):1262-78. doi:10.1016/j.cell.2014.05.010. Review. PubMed: 24906146. Free full-text available from PubMed Central: PMC4343198.

Komor AC, Badran AH, Liu DR. CRISPR-Based Technologies for the Manipulation of Eukaryotic Genomes. Cell. 2017 Apr 20;169(3):559. doi:10.1016/j.cell.2017.04.005. PubMed: 28431253.

Lander ES. The Heroes of CRISPR. Cell. 2016 Jan 14;164(1-2):18-28. doi:10.1016/j.cell.2015.12.041. Review. PubMed: 26771483.

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What are genome editing and CRISPR-Cas9? - Genetics Home ...

May 29, 2017 CRISPR-associated protein Cas9 (white) from Staphylococcus aureus based on Protein Database ID 5AXW. Credit: Thomas Splettstoesser (Wikipedia, CC BY-SA 4.0)

As CRISPR-Cas9 starts to move into clinical trials, a new study published in Nature Methods has found that the gene-editing technology can introduce hundreds of unintended mutations into the genome.

"We feel it's critical that the scientific community consider the potential hazards of all off-target mutations caused by CRISPR, including single nucleotide mutations and mutations in non-coding regions of the genome," says co-author Stephen Tsang, MD, PhD, the Laszlo T. Bito Associate Professor of Ophthalmology and associate professor of pathology and cell biology at Columbia University Medical Center and in Columbia's Institute of Genomic Medicine and the Institute of Human Nutrition.

CRISPR-Cas9 editing technologyby virtue of its speed and unprecedented precisionhas been a boon for scientists trying to understand the role of genes in disease. The technique has also raised hope for more powerful gene therapies that can delete or repair flawed genes, not just add new genes.

The first clinical trial to deploy CRISPR is now underway in China, and a U.S. trial is slated to start next year. But even though CRISPR can precisely target specific stretches of DNA, it sometimes hits other parts of the genome. Most studies that search for these off-target mutations use computer algorithms to identify areas most likely to be affected and then examine those areas for deletions and insertions.

"These predictive algorithms seem to do a good job when CRISPR is performed in cells or tissues in a dish, but whole genome sequencing has not been employed to look for all off-target effects in living animals," says co-author Alexander Bassuk, MD, PhD, professor of pediatrics at the University of Iowa.

In the new study, the researchers sequenced the entire genome of mice that had undergone CRISPR gene editing in the team's previous study and looked for all mutations, including those that only altered a single nucleotide.

The researchers determined that CRISPR had successfully corrected a gene that causes blindness, but Kellie Schaefer, a PhD student in the lab of Vinit Mahajan, MD, PhD, associate professor of ophthalmology at Stanford University, and co-author of the study, found that the genomes of two independent gene therapy recipients had sustained more than 1,500 single-nucleotide mutations and more than 100 larger deletions and insertions. None of these DNA mutations were predicted by computer algorithms that are widely used by researchers to look for off-target effects.

"Researchers who aren't using whole genome sequencing to find off-target effects may be missing potentially important mutations," Dr. Tsang says. "Even a single nucleotide change can have a huge impact."

Dr. Bassuk says the researchers didn't notice anything obviously wrong with their animals. "We're still upbeat about CRISPR," says Dr. Mahajan. "We're physicians, and we know that every new therapy has some potential side effectsbut we need to be aware of what they are."

Researchers are currently working to improve the components of the CRISPR systemits gene-cutting enzyme and the RNA that guides the enzyme to the right geneto increase the efficiency of editing.

"We hope our findings will encourage others to use whole-genome sequencing as a method to determine all the off-target effects of their CRISPR techniques and study different versions for the safest, most accurate editing," Dr. Tsang says.

The paper is titled, "Unexpected mutations after CRISPR-Cas9 editing in vivo." Additional authors are Kellie A. Schafer (Stanford University), Wen-Hsuan Wu (Columbia University Medical Center), and Diana G. Colgan (Iowa).

Explore further: Accurate DNA misspelling correction method

More information: Unexpected mutations after CRISPR-Cas9 editing in vivo, Nature Methods (2017).

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If a person has 3 months to live and they use crispr/cas9 to cure the cancer, and it works, what is the worst than can happen to him?

I'm not a biologist, so no idea how conceivable or absurd that idea might be. But then there's the whole thing with the Tasmanian devils. Anyway, you asked about worst cases, and that is one possible thing that people who are against this might be thinking.

Open a door, find 12 new doors. Like the knowledge that carbon nanos caused cancer but the powers-that-be decided we should use it any way because it was so convenient.

We are so screwed! This is worse than the advent of nuclear weapons.

this might cause regulated interests to think twice before deploying this for profit. It will not help us at all against weaponized CRISPR, though...

Crispr is the only way the human race will survive. Without it the machines rule. With crispr the human race increases everyone's IQ 10 fold. The vary smartest of us say "be very afraid of AI". Musk likened AI to a devil in a bottle. It's the 2nd level of our most brilliant people that can't see the danger AI poses. Raise everyone's IQ by 10X and we will make much better decisions and solve the current world's problems overnight.

Meatbrains are passe which is why we are so intent on replacing them.

Watch Forbidden Planet to see what happens when you mix intelligence with the need to survive to procreate.

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CRISPR gene editing can cause hundreds of unintended mutations - Phys.Org

Editas Medicine Demonstrates First Achievement of In Vivo Editing in Non-human Primate Retinas P&T Community Retinal tissue and genomic DNA were taken from within the sub-macular bleb region at six and 13 weeks and analyzed using Editas Medicine's novel sequencing method, UDiTaS, to accurately quantify all editing events. Gene editing was demonstrated to ... and more »

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Editas Medicine Demonstrates First Achievement of In Vivo Editing in Non-human Primate Retinas - P&T Community

March 8, 2017

Today, in vitro fertilization provides a way for couples to avoid passing potentially disease-causing genes to their offspring. A couple will undergo genetic screening. Tests will determine whether their unborn children are at risk. If embryos created through IVF show signs of such a genetic mutation, they can be discarded.

Flash forward a few years, and, instead of being discarded, those embryos can be repaired with new gene editing technologies. And those repairs will affect not only those children, but all their descendants

This is definitely new territory, said Pasquale Patrizio, M.D., director of the Yale Fertility Center and Fertility Preservation Program. We are at the verge of a huge revolution in the way disease is treated.

We are at the verge of a huge revolution in the way disease is treated.

In a move that seems likely to help clear the path for the use of gene editing in the clinical setting, on February 14 the Committee on Human Gene Editing, formed by the National Academy of Medicine and the National Academy of Sciences, recommended that research into human gene editing should go forward under strict ethical and safety guidelines. Among their concerns were ensuring that the technology be used to treat only serious diseases for which there is no other remedy, that there be broad oversight, and that there be equal access to the treatment. These guidelines provide a framework for discussion of technology that has been described as an ethical minefield and for which there is no government support in the United States.

A main impetus for the committees work appears to be the discovery and widespread use of CRISPR-Cas9, a defense that bacteria use against viral infection. Scientists including former Yale faculty member Jennifer Doudna, Ph.D., now at the University of California, Berkeley, and Emmanuelle Charpentier, Ph.D., of the Max Planck Institute for Infection Biology in Berlin, discerned that the CRISPR enzyme could be harnessed to make precision cuts and repairs to genes. Faster, easier, and cheaper than previous gene editing technologies, CRISPR was declared the breakthrough of the year in 2015 by Science magazine, and has become a basic and ubiquitous laboratory research tool. The committees guidelines, said scientists, physicians, and ethicists at Yale, could pave the way for thoughtful and safe use of this and other human gene editing technologies. In addition to CRISPR, the committee described three commonly used gene editing techniques; zinc finger nucleases, meganucleases, and transcription activator-like effector nucleases.

Patrizio, professor of obstetrics, gynecology, and reproductive sciences, said the guidelines are on the mark, especially because they call for editing only in circumstances where the diseases or disabilities are serious and where there are not alternative treatments. He and others cited such diseases as cystic fibrosis, sickle cell anemia, and thalassemia as targets for gene editing. Because they are caused by mutations in a single gene, repairing that one gene could prevent disease.

Peter Glazer, M.D. 87, Ph.D. 87, HS 91, FW 91, chair and the Robert E. Hunter Professor of Therapeutic Radiology and professor of genetics, said, The field will benefit from guidelines that are thoughtfully developed. This was a step in the right direction.

The panel recommended that gene editing techniques should be limited to deal with genes proven to cause or predispose to specific diseases. It should be used to convert mutated genes to versions that are already prevalent in the population. The panel also called for stringent oversight of the process and for a prohibition against use of the technology for enhancements, rather than to treat disease. As physicians, we understand what serious diseases are. Many of them are very well known and well characterized on a genetic level, Glazer said. The slippery slope is where people start thinking about modifications in situations where people dont have a serious disorder or disease.

Mark Mercurio, M.D., professor of pediatrics (neonatology), and director of the Program for Biomedical Ethics, echoed that concern. While he concurs with the panels recommendations, he urged a clear definition of disease prevention and treatment. At some point we are not treating, but enhancing. This in turn, he said, conjures up the nations own medical ethical history, which includes eugenics policies in the early 20th century that were later adopted in Nazi Germany. This has the potential to help a great many people, and is a great advance. But we need to be cognizant of the history of eugenics in the United States and elsewhere, and need to be very thoughtful in how we use this technology going forward, he said.

The new technology, he said, can lead to uncharted ethical waters. Pediatric ethics are more difficult, Mercurio said. It is one thing to decide for yourselfis this a risk Im willing to takeand another thing to decide for a child. It is another thing still further, which we have never had to consider, to decide for future generations.

Myron Genel, M.D., emeritus professor of pediatrics and senior research scientist, served on Connecticuts stem cell commission and four years on the Health and Human Services Secretary's Advisory Committee on Human Research Protections. He believes that Connecticuts guidelines on stem cell research provide a framework for addressing the issues associated with human gene editing. There is a whole regulatory process that has been evolved governing the therapeutic use of stem cells, he said. There are mechanisms that have been put in place for effective local oversight and national oversight for stem cell research.

Although CRISPR has been the subject of a bitter patent dispute between Doudna and Charpentier and The Broad Institute in Cambridge, Mass., a recent decision by the U.S. Patent Trial and Appeal Board in favor of Broad is unlikely to affect research at Yale and other institutions. Although Broad, an institute of Harvard and the Massachusetts Institute of Technology, can now claim the patent, universities do not typically enforce patent rights against other universities over research uses.

At Yale, scientists and physicians noted that gene editing is years away from human trials, and that risks remain. The issue now, said Glazer, is How do we do it safely? It is never going to be risk-free. Many medical therapies have side effects and we balance the risks and benefits. Despite its effectiveness, CRISPR is also known for whats called off-target risk, imprecise cutting and splicing of genes that could lead to unforeseen side effects that persist in future generations. CRISPR is extremely potent in editing the gene it is targeting, Glazer said. But it is still somewhat promiscuous and will cut other places. It could damage a gene you dont want damaged.

Glazer has been working with a gene editing technology called triple helix that hijacks DNAs own repair mechanisms to fix gene mutations. Triple helix, as its name suggests, adds a third strand to the double helix of DNA. That third layer, a peptide nucleic acid, binds to DNA and provokes a natural repair process that copies a strand of DNA into a target gene. Unlike CRISPR and other editing techniques, it does not use nucleases that cut DNA. This just recruits a process that is natural. Then you give the cell this piece of DNA, this template that has a new sequence, Glazer said, adding that triple helix is more precise than CRISPR and leads to fewer off-target effects, but is a more complex technology that requires advanced synthetic chemistry.

Along with several scientists across Yale, Glazer is studying triple helix as a potential treatment for cystic fibrosis, HIV/AIDS, spherocytosis, and thalassemia.

Adele Ricciardi, a student in her sixth year of the M.D./Ph.D. program, is working with Glazer and other faculty on use of triple helix to make DNA repairs in utero. She also supports the panels decision, but believes that more public discussion is needed to allay fears of misuse of the technology. In a recent presentation to her lab mates, she noted that surveys show widespread public concern about such biomedical advances. One study found that most of those surveyed felt it should be illegal to change the genes of unborn babies, even to prevent disease.

There is, I believe, a misconception of what we are using gene editing for, Ricciardi said. We are using it to edit disease-causing mutations, not to improve the intelligence of our species or get favorable characteristics in babies. We can improve quality of life in kids with severe genetic disorders.

This article was submitted by John Dent Curtis on March 8, 2017.

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Gene editing opens the door to a revolution in treating and preventing disease - Yale News

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Gene-delivery system prevents vision loss from inherited eye disease Science Daily "The promise of this technology is it localizes the drug to the photoreceptor cells, sparing the liver and kidney from exposure," said Krzysztof Palczewski, chairman of the Department of Pharmacology at the Case Western Reserve School of Medicine.

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Gene-delivery system prevents vision loss from inherited eye disease - Science Daily

Genetic changes in the cells lining the inside of the nose might someday help doctors diagnose lung cancer, a recent study suggests.

"The idea that you don't have to sample the disease tissue but can diagnose presence of disease using relatively accessible cells that are far from the tumor . . . is a paradigm that can impact many cancers," Dr. Avrum Spira from Boston University School of Medicine, a member of the study team, told Reuters Health by email.

The layer of cells that covers the surfaces of the body and lines the cavities is known as the epithelium. Researchers found that distinctive changes in gene activity in the nasal epithelium of lung cancer patients closely parallel the changes seen in lung epithelium and can distinguish between benign lung disease and cancer.

"I think the most interesting finding was the genomic changes in the nasal epithelium of lung cancer patients mirror so closely those found in the lower airway," Spira said.

The researchers thought the nose would be "a reasonable surrogate for the 'field of injury' in the bronchial airway," he added, but the surprisingly strong concordance between the nose and lower airway gave them the encouragement to develop a nasal biomarker for lung cancer detection.

"Pulmonary nodules represent a growing diagnostic dilemma in the U.S. as we have started to screen for lung cancer," Spira said. "A nasal swab that is highly sensitive for lung cancer in this setting would enable physicians to avoid unnecessary invasive biopsies in nodule patients who are unlikely to have lung cancer."

Past research has found that gene expression profiles from normal bronchial epithelial cells can distinguish smokers and former smokers with lung cancer from individuals with benign lung disease, and that nasal and bronchial epithelium respond similarly to tobacco smoke.

Spira's team sought to determine whether cancer-associated gene expression in the nasal epithelium might be useful for detecting lung cancer in current and former smokers.

They identified 535 genes that had different activity patterns in the nasal epithelium of patients with lung cancer versus those with benign disease.

Cancer-associated gene changes correlated significantly between nasal epithelium and bronchial epithelium samples, and the genes that were more active in nasal epithelium of patients with lung cancer were among the genes whose activity was most increased in bronchial epithelium of patients with cancer.

When researchers compared models doctors might use to determine the likelihood of lung cancer, nasal gene activity was more accurate than clinical risk factors alone for diagnosing lung cancer, according to the Journal of the National Cancer Institute report.

The combination of clinical factors and gene activity score accurately predicted cancer 91 percent of the time, compared to 79 percent for the model based on risk factors. The combined model also had 85 percent accuracy differentiating lung cancer from benign disease, compared to 73 percent.

"One of the big-picture messages for physicians is that molecular tests like this one are emerging as part of precision medicine approaches for early cancer detection," Spira said.

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Gene activity in the nose may signal lung cancer - Fox News

A new nasal test may allow patients suspected of having lung cancer to undergo a simple swab of their nose to determine if they have the disease.

Researchers at Boston University School of Medicine (BUSM) have found that a genomic biomarker in the nasal passage can accurately determine the likelihood of a lung lesion being malignant.

The findings, which appear online in the Journal of the National Cancer Institute, will allow physicians to confidently identify patients who are at low probability for having lung cancer, thus sparing them from costly and risky procedures.

The diagnostic evaluation of lung cancer among high-risk current and former smokers with lesions found on chest imaging (computed tomography or CT) represents a growing clinical challenge given the current clinical recommendations for routine CT screening of high-risk smokers. While there are guidelines for the management of pulmonary nodules, unnecessary, invasive follow-up procedures (including surgical lung biopsy) are frequently performed on patients who are ultimately diagnosed with benign disease.

"Our group previously derived and validated a bronchial epithelial gene-expression biomarker to detect lung cancer in current and former smokers. This innovation, available since 2015 as the Percepta Bronchial Genomic Classifier, is measurably improving lung cancer diagnosis," said corresponding author Avrum Spira, M.D., MSc, professor of medicine, pathology and bioinformatics at BUSM. "Given that bronchial and nasal epithelial gene expressions are similarly altered by cigarette smoke exposure, we sought to determine in this study if cancer-associated gene expression might also be detectable in the more readily accessible nasal epithelium."

After examining nasal epithelial brushings from current and former smokers undergoing diagnostic evaluation for pulmonary lesions suspicious for lung cancer, the researchers determined that the nasal airway epithelial field of lung cancer-associated injury in smokers extends to the nose and has the potential of being a non-invasive biomarker for lung cancer detection.

"There is a clear and growing need to develop additional diagnostic approaches for evaluating pulmonary lesions to determine which patients should undergo CT surveillance or invasive biopsy. The ability to test for molecular changes in this 'field of injury' allows us to rule out the disease earlier without invasive procedures," added Spira, who is also director of the BU-BMC Cancer Center and a pulmonologist at Boston Medical Center (BMC).

"Our findings clearly demonstrate the existence of a cancer-associated airway field of injury that also can be measured in nasal epithelium," added Marc Lenburg, Ph.D., professor of medicine at BUSM and co-senior author. "We find that nasal gene expression contains information about the presence of cancer that is independent of standard clinical risk factors, suggesting that nasal epithelial gene expression might aid in lung cancer detection. Moreover, the nasal samples can be collected non-invasively with little instrumentation or advanced training."

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Study Finds Biomarker for Lung Cancer Detection in the Nasal Passages of Smokers - Bioscience Technology

February 27, 2017 Lung CA seen on CXR. Credit: James Heilman, MD/Wikipedia

A new nasal test may allow patients suspected of having lung cancer to undergo a simple swab of their nose to determine if they have the disease.

Researchers at Boston University School of Medicine (BUSM) have found that a genomic biomarker in the nasal passage can accurately determine the likelihood of a lung lesion being malignant.

The findings, which appear online in the Journal of the National Cancer Institute, will allow physicians to confidently identify patients who are at low probability for having lung cancer, thus sparing them from costly and risky procedures.

The diagnostic evaluation of lung cancer among high-risk current and former smokers with lesions found on chest imaging (computed tomography or CT) represents a growing clinical challenge given the current clinical recommendations for routine CT screening of high-risk smokers. While there are guidelines for the management of pulmonary nodules, unnecessary, invasive follow-up procedures (including surgical lung biopsy) are frequently performed on patients who are ultimately diagnosed with benign disease.

"Our group previously derived and validated a bronchial epithelial gene-expression biomarker to detect lung cancer in current and former smokers. This innovation, available since 2015 as the Percepta Bronchial Genomic Classifier, is measurably improving lung cancer diagnosis," said corresponding author Avrum Spira, MD, MSc, professor of medicine, pathology and bioinformatics at BUSM. "Given that bronchial and nasal epithelial gene expressions are similarly altered by cigarette smoke exposure, we sought to determine in this study if cancer-associated gene expression might also be detectable in the more readily accessible nasal epithelium."

After examining nasal epithelial brushings from current and former smokers undergoing diagnostic evaluation for pulmonary lesions suspicious for lung cancer, the researchers determined that the nasal airway epithelial field of lung cancer-associated injury in smokers extends to the nose and has the potential of being a non-invasive biomarker for lung cancer detection.

"There is a clear and growing need to develop additional diagnostic approaches for evaluating pulmonary lesions to determine which patients should undergo CT surveillance or invasive biopsy. The ability to test for molecular changes in this 'field of injury' allows us to rule out the disease earlier without invasive procedures," added Spira, who is also director of the BU-BMC Cancer Center and a pulmonologist at Boston Medical Center (BMC).

"Our findings clearly demonstrate the existence of a cancer-associated airway field of injury that also can be measured in nasal epithelium," added Marc Lenburg, PhD, professor of medicine at BUSM and co-senior author. "We find that nasal gene expression contains information about the presence of cancer that is independent of standard clinical risk factors, suggesting that nasal epithelial gene expression might aid in lung cancer detection. Moreover, the nasal samples can be collected non-invasively with little instrumentation or advanced training."

Explore further: Study validates effectiveness of genomic test for lung cancer detection

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Study finds biomarker for lung cancer detection in the nasal passages of smokers - Medical Xpress

Researchers provide further evidence of how gene mutations in a certain brain region might fuel behaviors associated with obsessive-compulsive disorder. The findings could pave the way for new treatments for the condition.

Obsessive-compulsive disorder is a condition characterized by uncontrollable thoughts, obsessions, and compulsions.

Obsessions include repetitive thoughts or mental images that trigger anxiety, while compulsions refer to the urge to repeat certain behaviors in response to obsessions. Common examples of compulsions include excessive hand-washing, arranging items in a particular way, and compulsive counting.

OCD is estimated to affect around 1 percent of adults in the United States. Of these adults, 50 percent have severe OCD, which can significantly interfere with daily life.

While the precise causes of OCD are unclear, previous studies have suggested that the disorder may be caused by specific gene mutations.

In the new study, researchers from Northwestern University in Chicago, IL, have pinpointed gene mutations in the corticostriatal region of the brain that led to OCD-like behaviors in mice.

Lead author Anis Contractor, associate professor of physiology at Feinberg School of Medicine, and colleagues recently reported their findings in the journal Cell Reports.

In humans and mice, the corticostriatal brain region is responsible for regulating repetitive behavior. "People with OCD are known to have abnormalities in function of corticostriatal circuits," notes Contractor.

By analyzing this brain region in mice, Contractor and colleagues identified a number of synaptic receptors - called kainate receptors (KARs) - that play a key role in the development of the corticostriatal region.

The researchers then set out to investigate whether disrupting KAR genes in mice - thereby eliminating KARs - might induce repetitive behavior in the rodents. They found this was the case.

Mice whose KAR genes were erased displayed a number of OCD-like behaviors, such as over-grooming and repeatedly digging in their bedding.

The team says these findings provide further evidence that KAR genes play a role in OCD in humans, and a possible biological mechanism.

"A number of studies have found mutations in the kainate receptor genes that are associated with OCD or other neuropsychiatric and neurodevelopmental disorders in humans.

I believe our study, which found that a mouse with targeted mutations in these genes exhibited OCD-like behaviors, helps support the current genetic studies on neuropsychiatric and neurodevelopmental disorders in humans."

Anis Contractor

The team suggests that in the future, KAR genes could be a target for the development of new drugs to treat OCD.

Learn how exposure therapy might help treat people with OCD.

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Gene mutations in brain linked to OCD-like behavior - Medical News ... - Medical News Today

February 20, 2017 Credit: CC0 Public Domain

Gene editing techniques developed in the last five years could help in the battle against cancer and inherited diseases, a University of Exeter scientist says.

Dr Edze Westra said the ability to splice selected DNA into cells with great precision would become "super important" in the next two decades. There could be benefits for generations of people affected by cancer, failing vision and the diseases of old age or bad genes.

"There is always a risk with this kind of technology and fears about designer babies and we have started having discussions about that so we can understand the consequences and long-term risks," said Dr Westra, of the Environment and Sustainability Institute on the University of Exeter's Penryn Campus in Cornwall. "I think in the coming decades gene editing will become super important, and I think we will see it being used to cure some inherited diseases, to cure cancers, to restore sight to people by transplanting genes. I think it will definitely have massive importance."

On Tuesday, two highly influential academic bodies in the US shook up the scientific world with a report that, for the first time, acknowledged the medical potential of editing inherited genes. The National Academy of Sciences and National Academy of Medicine ruled that gene editing of the human "germline"eggs, sperm and embryosshould not be seen as a red line in medical research.

Many critics insist that powerful new gene editing techniques should never be used to alter inherited DNA. They argue that such a move would be the start of a slippery slope leading to "designer" babies with selected features such as blue eyes, high intelligence or sporting prowess.

But the two pillars of the American scientific establishment said that with necessary safeguards, future use of germline gene editing to treat or prevent disease and disability was a "realistic possibility that deserves serious consideration".

Dr Westra is taking part in a discussion on gene editing and its potential implications for society at the American Association for the Advancement of Science (AAAS) annual meeting in Boston, Massachusetts. He said gene editing technology not only held out the promise of fixing genetic faults, but could be used to turn cells into miniature factories that churned out therapeutic chemicals or antibodies.

One application was the use of "gene drives" that increase the prevalence of a certain trait in a population. For instance, gene editing machinery placed inside the cells of large numbers of malaria transmitting mosquitoes could prevent them spreading the organism that causes the disease to humans.

The most promising form of gene editing, known as CRISPR/Cas9, was first demonstrated in 2012. It employs a defence system bacteria use to protect themselves against viruses. A carefully targeted enzyme is used as chemical "scissors" that cut through specific sections of double stranded DNA. Then the cell's own DNA repair machinery can be exploited to insert the "pasted" genetic material.

Dr Westra said: "Gene editing is causing a true revolution in science and medicine because it allows for very precise DNA surgery. "A mutation in a gene that causes disease can now be repaired using CRISPR."

Explore further: No designer babies, but gene editing to avoid disease? Maybe

A research team from the United States and Canada has developed and successfully tested new computational software that determines whether a human DNA sample includes an epigenetic add-on linked to cancer and other adverse ...

Gene discovery research is uncovering new information about similarities and differences underlying various neurodevelopmental disorders.

A University of Toronto (U of T) study on fruit flies has uncovered a gene that could play a key role in obesity in humans.

Our genes play a significant role in how anxious we feel when faced with spatial and mathematical tasks, such as reading a map or solving a geometry problem, according to a new study by researchers from King's College London.

Gene editing techniques developed in the last five years could help in the battle against cancer and inherited diseases, a University of Exeter scientist says.

(Medical Xpress)A team of researchers with New England Biolabs Inc. (NEB) has found that sequenced DNA samples held in public databases had higher than expected low-frequency mutation error rates. In their paper published ...

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Gene editing could help tackle cancer and inherited diseases - Medical Xpress

FierceBiotech

Gene therapy treats muscle-wasting disease in dogs Science Daily Work on gene therapy is showing significant progress for restoring muscle strength and prolonging lives in dogs with a previously incurable, inherited neuromuscular disease. UW Medicine Institute for Stem Cell and Regenerative Medicine scientists are ... Gene therapy tried in dogs with muscle disease could prove useful for peopleFierceBiotech all 2 news articles »

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Gene therapy treats muscle-wasting disease in dogs - Science Daily

THE 1997 FILM Gattaca predicted a near future in which cities are powered by vast solar thermal arrays, humans launch manned missions to Saturns moons, and doctors design super smart and strong babies. A generation later, it is the gene editing that is proving most prescient.

Over the past decade, huge advances in gene-editing techniques have enabled researchers to slice up and rewrite DNA with incredible precision. At the forefront of the ensuing revolution is the CRISPR-Cas9, a technology derived from bacteria that enables scientists to snip and repair DNA, nucleotide by nucleotide, quickly and cheaply. The potential uses are vast. And so are the ethical quandaries.

The National Academies of Sciences and the National Academy of Medicine convened a panel to recommend guidelines for the use of powerful gene-editing tools. The results, released this week, are thoughtful and should for the moment, anyway channel research and testing in unambiguously positive directions.

CRISPR can be used in basic laboratory research, revealing how disease works on the molecular level. This is similar enough to other types of lab research that it requires no novel scientific or ethical standards. Researchers can also treat live humans with gene editing technologies, for example by taking immune cells out of the body, altering them and re-inserting them to fight an advanced cancer. Therapies such as these are already under development, and although researchers have to be cautious about off-target gene slicing, existing rules governing the development of medical treatments should suffice.

The ethics get much trickier when researchers want to change the DNA in reproductive cells, which would alter the genes that parents pass to children, forever. Doing so could prevent vast amounts of human suffering. But there is a problem of consent: Future generations have no say in their alteration. Disability communities would no doubt feel threatened and stigmatized, because gene editing could be used to essentially remove their type from the gene pool. Changes made to enhance human offspring, rather than simply to combat disease and disability, could redefine what it means to be human, while those to whom these techniques are unavailable would risk becoming a genetic underclass. A line would have to be drawn between heritable changes that are clearly valuable and those that risk unnecessarily humiliating people, destabilizing society and changing the nature of humanity.

The panel attempted to draw a preliminary line and put it in the right place. Heritable changes should be attempted only when scientists are convinced that specific genes cause or strongly predispose people to getting a serious disease or a condition, and when they know what normal genetic code should look like. They should only intervene when there are no reasonable alternatives available to families, and when real-world evidence shows that the benefits outweigh the risks.

The debate will not and should not end there. But before society has a full chance to process these questions, the panels approach is the right one. The goal should be to stop crippling diseases, not to build designer babies.

Originally posted here:
A way forward in gene editing - Washington Post

Shinya Yamanaka's 2006 discovery of induced pluripotent stem cells (iPSCs) ignited a revolution in the field of stem cell biology (1). For the first time, nearly all human somatic tissues could be produced from iPSCs reprogrammed from blood or skin cells, in a process that took only weeks. This advance was particularly crucial for obtaining surrogate tissues from cell types that are otherwise difficult to procure and do not readily expand in vitro, such as cardiac or neural cells. Additionally, many ethical concerns are avoided, because this technology uses a patient's own genetic material to create iPSCs rather than relying on embryonic stem cells. In the aftermath of Yamanaka's discovery, entire biomedical industries have developed around the promise of using human iPSCs (hiPSCs) and their derivatives for in vitro disease modeling, drug screening, and cell therapy (2).

The hiPSC technology has had a particularly notable impact in cardiac regenerative medicine, a field where scientists and clinicians have been working to devise new methods to better understand how cardiovascular disease manifests and how to restore cardiovascular function after disease strikes (3). The heart is limited in its ability to regenerate lost cardiomyocytes (beating heart muscle cells), following an adverse event such as a heart attack (4). Cardiomyocytes derived from hiPSCs (hiPSC-CMs) may represent a potential replacement option for dead cells in such a scenario. However, certain issues remain to be addressed, such as whether hiPSC-CMs can integrate with host myocardial tissue in the long term (5).

While using hiPSC-CMs for in vivo cell therapy may become practical in the future, employing hiPSC-CMs for high-throughput drug discovery and screening is becoming a reality in the present (6). Cardiovascular diseases can be recapitulated in a dish with patient-specific hiPSC-CMs. For example, if a patient exhibits a cardiac arrhythmia caused by a genetic abnormality in a sarcomeric protein or ion channel, that same rhythm problem can be recapitulated in vitro (7). Thanks to advances in hiPSC differentiation protocols, hiPSC-CMs can now be mass-produced to study cardiovascular disease mechanisms in vitro (8).

My graduate thesis in the laboratories of Joseph Wu and Sean Wu at Stanford University focused on in vitro applications of hiPSC-CMs for cardiovascular disease modeling and for high-throughput screening of chemotherapeutic compounds to predict cardiotoxicity. I initially embarked on a project using hiPSC-CMs to model viral myocarditis, a viral infection of the heart, caused by the B3 strain of coxsackievirus (9). I began by demonstrating that hiPSC-CMs express the receptors necessary for viral internalization and subsequently found that hiPSC-CMs were highly susceptible to coxsackievirus infection, exhibiting viral cytopathic effect within hours of infection. I also identified compounds that could alleviate coxsackievirus infection on hiPSC-CMs, a translationally relevant finding, as there remains a shortage of treatments for viral myocarditis.

Using a genetically modified variant of coxsackievirus B3 expressing luciferase, I developed a screening platform for assessing the efficacy of antiviral compounds. Pretreatment with interferon-, ribavirin, or pyrrolidine dithiocarbamate markedly suppressed viral replication on hiPSC-CMs by activating intracellular antiviral response and viral protein clearance pathways. These compounds alleviated viral replication in a dose-dependent fashion at low concentrations without causing cellular toxicity.

I next sought to use hiPSC-CMs to screen anticancer chemotherapeutic compounds for their off-target cardiovascular toxicities (10). Cardiotoxicity represents a major cause of drug withdrawal from the pharmaceutical market, and several chemotherapeutic agents can cause unintended cardiovascular damage (11). Using cultured hiPSC-CMs, I evaluated 21 U.S. Food and Drug Administrationapproved tyrosine kinase inhibitors (TKIs), commonly prescribed anticancer compounds, for their cardiotoxic potential. HiPSC-CMs express the major tyrosine kinase receptor proteins such as the insulin, insulin-like growth factor (IGF), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) receptors, lending validity to this cellular model.

Initially, human induced pluripotent stem cells (hiPSCs) can be produced by reprogramming skin or blood cells by nonviral or viral reprogramming methods. Cardiac differentiation protocols allow for the creation of cardiomyocytes derived from hiPSCs (hiPSC-CMs) for downstream applications, including in vitro disease modeling, drug screening, and regenerative cell therapy.

With data from a battery of cellular apoptosis, contractility, electrophysiology, and signaling assays, I generated a cardiac safety index to help align in vitro toxicity data to clinical drug safety guidelines (12). From the safety index, I determined that a subclass of VEGF receptor 2/PDGF receptorinhibiting tyrosine kinase inhibitors, some of which exhibit toxicity clinically, also elicited cardiotoxicities in hiPSC-CMs. These manifested as substantial alterations in cellular electrophysiology, contractility, and viability when administered at clinically relevant concentrations. I also discovered that cotreatment with either IGF or insulin partially rescued TKI-induced toxicity by up-regulating antiapoptotic signaling pathways. This work could prove useful for groups aiming to develop effective screening platforms to assess new chemotherapeutic compounds for cardiotoxic side effects.

I also collaborated with the Center for the Advancement of Science in Space (CASIS) to send a sample of hiPSC-CMs to the International Space Station. As humankind ventures beyond our home planet, it is imperative that we better understand how the heart functions for long periods of time in microgravity. Analysis of these hiPSC-CMs revealed microgravity-induced alterations in metabolic gene expression and calcium handling (13).

In recent years, the stem cell field has experienced an explosion of studies using hiPSC-CMs as a model cellular system to study cardiovascular biology. As improvements in hiPSC-CM mass production continue, we will see a rise in studies using these cells for disease modeling and drug screening. Thus, although hiPSC-CM technology is in its infancy, it holds great potential to improve cardiovascular health.

PHOTO: COURTESY OF A. SHARMA

FINALIST

Arun Sharma

Arun Sharma received his undergraduate degree from Duke University and a Ph.D. from Stanford University. Having completed a postdoctoral fellowship at the Harvard Medical School, Sharma is now a senior research fellow jointly appointed at the Smidt Heart Institute and Board of Governors Regenerative Medicine Institute at the Cedars-Sinai Medical Center in Los Angeles. His research seeks to develop in vitro platforms for cardiovascular disease modeling and drug cardiotoxicity assessment. http://www.sciencemag.org/content/367/6483/1206.1

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Stem cells to help the heart - Science Magazine

Join journalists from around the world covering the American College of Medical Genetics and Genomics Annual Clinical Genetics Meeting March 17-21, 2020 in San Antonio, TX

BETHESDA, Md., Feb. 24, 2020 /PRNewswire/ -- The American College of Medical Genetics and Genomics (ACMG) heads to a new destination in sunny San Antonio, Texas in 2020. Named one of the fastest growing meetings in the USA by Trade Show Executive Magazine, the ACMG Annual Clinical Genetics Meeting continues to provide groundbreaking research and news about the latest advances in genetics, genomics and personalized medicine. To be held March 17-21, the 2020 ACMG Annual Meeting will feature more than 40 scientific sessions as well as three Short Courses, a variety of workshops, TED-Style talks and satellite symposia, and more than 750 poster presentations on emerging areas of genetic and genomic medicine.

Founded in 1991, the American College of Medical Genetics and Genomics (ACMG) is the only nationally recognized medical society dedicated to improving health through the clinical practice of medical genetics and genomics. (PRNewsfoto/American College of Medical G...)

Interview those at the forefront in medical genetics and genomics, connect in person with new sources and get story ideas on the clinical practice of genetics and genomics in healthcare today and for the future. Learn how genetics and genomics research is being integrated and applied into medical practice.

Topics include gene editing, cancer genetics, molecular genomics, exome sequencing, pre- and perinatal genetics, biochemical/metabolic genetics, genetic counseling, health services and implementation, legal and ethical issues, therapeutics and more.

Credentialed media representatives on assignment are invited to attend and cover the ACMG Annual Meeting on a complimentary basis. Contact Reymar Santos at rsantos@acmg.net for the Press Registration Invitation Code, which will be needed to register atwww.acmgmeeting.net.

Abstracts of presentations are available online at http://www.acmgmeeting.net. A few 2020 ACMG Annual Meeting highlights include:

Program Highlights:

Cutting Edge Scientific Concurrent Sessions:

Three half-day Genetics Short Courses on Monday, March 16 and Tuesday, March 17:

Photo/TV Opportunity: The ACMG Foundation for Genetic and Genomic Medicine will present bicycles to local children with rare genetic diseases at the Annual ACMG Foundation Day of Caring on Friday, March 20 from 10:30 AM 11:00 AM at the Henry B. Gonzlez Convention Center.

Social Media for the 2020 ACMG Annual Meeting: As the ACMG Annual Meeting approaches, journalists can stay up to date on new sessions and information by following the ACMG social media pages on Facebook, Twitterand Instagram and by usingthe hashtag #ACMGMtg20 for meeting-related tweets and posts.

Note be sure to book your hotel reservations early.

The ACMG Annual Meeting website has extensive information atwww.acmgmeeting.net.

About the American College of Medical Genetics and Genomics (ACMG) and the ACMG Foundation for Genetic and Genomic Medicine

Founded in 1991, the American College of Medical Genetics and Genomics (ACMG) is the only nationally recognized medical society dedicated to improving health through the clinical practice of medical genetics and genomics and the only medical specialty society in the US that represents the full spectrum of medical genetics disciplines in a single organization. The ACMG is the largest membership organization specifically for medical geneticists, providing education, resources and a voice for more than 2,400 clinical and laboratory geneticists, genetic counselors and other healthcare professionals, nearly 80% of whom are board certified in the medical genetics specialties. ACMG's mission is to improve health through the clinical and laboratory practice of medical genetics as well as through advocacy, education and clinical research, and to guide the safe and effective integration of genetics and genomics into all of medicine and healthcare, resulting in improved personal and public health. Four overarching strategies guide ACMG's work: 1) to reinforce and expand ACMG's position as the leader and prominent authority in the field of medical genetics and genomics, including clinical research, while educating the medical community on the significant role that genetics and genomics will continue to play in understanding, preventing, treating and curing disease; 2) to secure and expand the professional workforce for medical genetics and genomics; 3) to advocate for the specialty; and 4) to provide best-in-class education to members and nonmembers. Genetics in Medicine, published monthly, is the official ACMG journal. ACMG's website (www.acmg.net) offers resources including policy statements, practice guidelines, educational programs and a 'Find a Genetic Service' tool. The educational and public health programs of the ACMG are dependent upon charitable gifts from corporations, foundations and individuals through the ACMG Foundation for Genetic and Genomic Medicine.

Raye Alford, PhDralford@acmg.net

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SOURCE American College of Medical Genetics and Genomics

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Last Chance for Press Registration! Countdown to the 2020 ACMG Annual Clinical Genetics Meeting - Yahoo Finance

Image: Professor Chris Lord andDr Stephen Pettitt next to the olaparib display in the Science Museum's medicine galleries

The Science Museum's new 24 millionmedicine galleriesshowcases pioneering research from The Institute of Cancer Research, London, as part of its story of modern medicine.

The new galleries, which have transformed the first floor of the world-famous museum, explore humanity's relationship with medicine and health through more than 500 years of history.

Included in the exhibition are extraordinary medical artefacts from the collections of Henry Wellcome and the Science Museum Group, including the world's first MRI scanner, Fleming's penicillin mould, a professional pianist's prosthetic arm and robotic surgery equipment.

Science MuseumLatesare adults-only, after-hours theme nights that take place in the museum on the last Wednesday of every month. Tonight's (Wednesday 29 January) Lates event isMedicine Lates.

Follow #smLates on Twitter

The museum chose to showcase the ICR's pioneering research underpinning the development of targeted drug olaparib, which has transformed the lives of tens of thousands of women with breastand ovariancancers.

Olaparib's origins lie in ICR research into the BRCA genes in the 1990s, when our scientists tracked down the BRCA2 gene.

A decade after the identification of BRCA2, ICR researchers found that targeting a DNA repair protein called PARP was a potential way to kill cancer cells with a faulty BRCA gene. This helped lead to the development of olaparib, and other so-called PARP inhibitors.

The gallery features plates which replicate the original ICR experiment to successfully show that olaparib specifically kills cancer cells with defects in their BRCA genes, while leaving healthy cells unaffected.

You can see these in the Medicine and Bodies gallery, which explores how the search to understand more about the human body has transformed medicine.

Displayed alongside Crick and Watson's molecular DNA model, the plates represent how understanding the genetic basis of cancer has transformed our ability to treat it through the creation of targeted therapies.

Professor Chris Lord,Deputy Head of the Breast Cancer Now Toby Robins Research CentreandDivision of Breast Cancer Researchat the ICR (pictured above), said:

"The fact that the Science Museum have chosen to highlight PARP inhibitors in their new gallery is a real testament to how cancer research can genuinely lead to improvements in the treatment of the disease. We are immensely proud of this, as are the other labs across the world who also contributed to these discoveries."

"Despite PARP inhibitors now being highlighted in Science Museum, this is not the end for us we are still working very hard at the ICR to think about how we can improve the effectiveness of these drugs and to make sure that each patient receives the best possible treatment approach."

Daisy Henesy, the ICRs Public Engagement Officer, said:

"It's a thrill to see the ICR's research showcased alongside other huge advances in modern medicine, and richly deserved.

"I urge everyone to visit the new Science Museum galleries and have a look for yourself and don't forget to tweet us with any pictures @ICR_Londonand let us know what you think!"

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ICR research showcased in major new Science Museum gallery documenting history of medicine - The Institute of Cancer Research

An emergency room physician, initially unable to diagnose a disoriented patient, finds on the patient a wallet-sized card providing access to his genome, or all his DNA. The physician quickly searches the genome, diagnoses the problem and sends the patient off for a gene-therapy cure. Thats what a Pulitzer prize-winning journalist imagined 2020 would look like when she reported on the Human Genome Project back in 1996.

A new era in medicine?

The Human Genome Project was an international scientific collaboration that successfully mapped, sequenced and made publicly available the genetic content of human chromosomes or all human DNA. Taking place between 1990 and 2003, the project caused many to speculate about the future of medicine. In 1996, Walter Gilbert, a Nobel laureate, said, The results of the Human Genome Project will produce a tremendous shift in the way we can do medicine and attack problems of human disease. In 2000, Francis Collins, then head of the HGP at the National Institutes of Health, predicted, Perhaps in another 15 or 20 years, you will see a complete transformation in therapeutic medicine. The same year, President Bill Clinton stated the Human Genome Project would revolutionize the diagnosis, prevention and treatment of most, if not all, human diseases.

It is now 2020 and no one carries a genome card. Physicians typically do not examine your DNA to diagnose or treat you. Why not? As I explain in a recent article in the Journal of Neurogenetics, the causes of common debilitating diseases are complex, so they typically are not amenable to simple genetic treatments, despite the hope and hype to the contrary.

Causation is complex

The idea that a single gene can cause common diseases has been around for several decades. In the late 1980s and early 1990s, high-profile scientific journals, including Nature and JAMA, announced single-gene causation of bipolar disorder, schizophrenia and alcoholism, among other conditions and behaviors. These articles drew massive attention in the popular media, but were soon retracted or failed attempts at replication. These reevaluations completely undermined the initial conclusions, which often had relied on misguided statistical tests. Biologists were generally aware of these developments, though the follow-up studies received little attention in popular media.

There are indeed individual gene mutations that cause devastating disorders, such as Huntingtons disease. But most common debilitating diseases are not caused by a mutation of a single gene. This is because people who have a debilitating genetic disease, on average, do not survive long enough to have numerous healthy children. In other words, there is strong evolutionary pressure against such mutations. Huntingtons disease is an exception that endures because it typically does not produce symptoms until a patient is beyond their reproductive years. Although new mutations for many other disabling conditions occur by chance, they dont become frequent in the population.

Instead, most common debilitating diseases are caused by combinations of mutations in many genes, each having a very small effect. They interact with one another and with environmental factors, modifying the production of proteins from genes. The many kinds of microbes that live within the human body can play a role, too.

Since common serious diseases are rarely caused by single-gene mutations, they cannot be cured by replacing the mutated gene with a normal copy, the premise for gene therapy. Gene therapy has gradually progressed in research along a very bumpy path, which has included accidentally causing leukemia and at least one death, but doctors recently have been successful treating some rare diseases in which a single-gene mutation has had a large effect. Gene therapy for rare single-gene disorders is likely to succeed, but must be tailored to each individual condition. The enormous cost and the relatively small number of patients who can be helped by such a treatment may create insurmountable financial barriers in these cases. For many diseases, gene therapy may never be useful.

A new era for biologists

The Human Genome Project has had an enormous impact on almost every field of biological research, by spurring technical advances that facilitate fast, precise and relatively inexpensive sequencing and manipulation of DNA. But these advances in research methods have not led to dramatic improvements in treatment of common debilitating diseases.

Although you cannot bring your genome card to your next doctors appointment, perhaps you can bring a more nuanced understanding of the relationship between genes and disease. A more accurate understanding of disease causation may insulate patients against unrealistic stories and false promises.

[ Youre smart and curious about the world. So are The Conversations authors and editors. You can read us daily by subscribing to our newsletter. ]

Ari Berkowitz, Presidential Professor of Biology; Director, Cellular & Behavioral Neurobiology Graduate Program, University of Oklahoma

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Image: Reuters

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Why Sequencing the Human Genome Failed to Change the Face of Science - The National Interest Online

Pumping iron: A gene called BOLA2 helps proteins capture iron, which is crucial for red blood cells to transport oxygen.

Design Cells / Science Photo Library

IN BRIEF

Extra copies of a gene called BOLA2 predispose people to autism and may protect against iron deficiency, according to a new study1.

Repeats of the gene make people susceptible to deletion or duplication of a region on chromosome 16 that is tied to autism. The benefit of anemia prevention may explain why the repeats evolved despite their potential harm.

The rearrangement is highly compensated by an adaptation, says co-lead researcher Alexandre Reymond, director of the Center for Integrative Genomics at the Universit de Lausanne in Switzerland.

The extra copies are unique to humans, who typically have six. Our closest ancestors Neanderthals, Denisovans and chimpanzees each have only two, suggesting that the repeats confer an important evolutionary advantage. What that advantage is, however, has been a mystery.

One clue lies in the genes function: BOLA2 helps proteins capture iron. Having fewer repeats is associated with anemia, the researchers found.

Its very interesting, says Emily Casanova, research assistant professor of biomedical sciences at the University of South Carolina in Greenville, who was not involved in the study. My only question is why BOLA2 duplications would have been selected for. What might have been some of the driving factors?

BOLA2 repeats flank a stretch of chromosome 16 called 16p11.2, a hotspot for deletions and duplications that can lead to autism. As eggs and sperm form, the BOLA2 repeats cause DNA to break and rejoin in unusual ways in the 16p11.2 region.

Reymond and his colleagues counted BOLA2 repeats in 130 people who have a deletion of 16p11.2 and in the genetic sequences of 635 controls from two data repositories.

They found that 16p11.2 deletion carriers tend to have fewer BOLA2 repeats than controls do: four as opposed to the usual six. The findings suggest that some BOLA2 copies are lost when deletions in 16p11.2 form.

Because BOLA2 helps proteins latch onto iron, the researchers wondered whether too little of it has consequences for red blood cells; iron is crucial for the cells to transport oxygen.

The researchers analyzed blood samples and medical information from 83 deletion carriers. They found that 8 of the 15 people with only three BOLA2 repeats have signs of anemia, compared with 5 of 68 who have four or more repeats.

The researchers found a similar pattern when they examined genetic and medical information for 379,474 people in the UK Biobank. They found anemia in 20 percent of people with a 16p11.2 deletion, compared with 5 percent of controls. (Anemias prevalence in people with a duplication is no different than in controls.)

Mice missing a copy of 16p11.2 also have low iron levels, and their red blood cells show signs of mild anemia, the team found. Two strains of mice that lack one or both of their copies of BOLA2 show similar traits. The findings were published 7 November in the American Journal of Human Genetics.

The results jibe with those from a March study, in which researchers found an increased risk of anemia in people with a 16p11.2 deletion2.

The link of the BOLA2 copy number to anemia is quite strong, says Bernard Crespi, professor of evolutionary biology at Simon Fraser University in Vancouver, Canada, who was not involved in the study. Why humans evolved a higher number of BOLA2 genes, thats the hard question.

The factors that selected for extra BOLA2 copies remain a mystery. Having extra BOLA2 might have been beneficial as early humans shifted away from a diet based on red meat to one that is less rich in iron, Reymond says. Or perhaps the repeats arose because they protect people from infections, he says: Many pathogens depend on iron they scavenge from their hosts, and BOLA2 might interfere with that process.

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Gene repeats tied to autism may prevent anemia - Spectrum

Nine months after receiving an infusion of gene-edited stem cells, a patient in a closely followed clinical study is free from the blood transfusions necessary for those who live with severe beta-thalassemia, an inherited disease caused by defective red blood cells.

Another patient has not suffered a painful sickle cell crisis in the four months since receiving the same gene-editing therapy in a separate trial for the related blood condition.

The results, unveiled Tuesday by partners CRISPR Therapeutics and Vertex, offer an initial glimpse at the potential for CRISPR-based gene editing to change the course of hereditary disorders like sickle cell and beta-thalassemia.

"This is a very important landmark, not just for us as a company but for the field," said CRISPR CEO Samarth Kulkarni in an interview.

The two patients are the first to be treated in the companies' Phase 1/2 trials, which are the furthest along among drugmaker-led efforts to translate the breakthrough science into medicines and, possibly, genetic cures.

Only so much can be drawn from their experience, and side effects remain a concern in a field that's advanced rapidly from laboratory and animal testing into humans. Fuller data will also be needed to assess if patients improve over time, and remain transfusion- or crisis-free.

But Vertex and CRISPR Therapeutics report that their therapy, dubbed CTX001, appears to have accomplished what it was designed to do. Both patients achieved levels of hemoglobin the oxygen-carrying protein rendered dysfunctional by sickle cell disease and beta-thalassemia that approach what's considered normal, or at least mildly anemic.

Tuesday's disclosure was highly anticipated, both for its implications for gene-editing therapies and as the first clinical update from CRISPR Therapeutics, a Switzerland-headquartered biotech that went public in the U.S. three years ago.

Progress from CRISPR's pipeline also comes as Vertex, which inked a research deal with the smaller drugmaker in 2015, expands beyond the cystic fibrosis research for which it's known. Bets in newer technologies like CRISPR and cell therapy look to play a part in that plan.

CTX001is built from stem or progenitor cells extracted from each patient scheduled to be treated. Those cells are then genetically modified outside the body using CRISPR-cas9technology to spur production of a type of hemoglobin that's present at birth but normally replaced shortly thereafter.

Put simpler, CRISPR and Vertex hope to recreate a condition known as hereditary persistence of fetal hemoglobin, substituting the usually short-lived fetal hemoglobin for the mutant beta-globin found in sickle cell and beta-thalassemia patients.

In the first patient with beta-thalassemia, total hemoglobin reached 11.9 grams per deciliter, of which 10.1 was classified as fetal, at nine months post treatment.According to the World Health Organization, mild anemia is classified as over 11 g/dL and normal as over 13 g/dL.

Prior to enrolling in the study, the individual needed more than one blood transfusion per month. After nine months following treatment without a single transfusion, CRISPR and Vertex said the patient is now transfusion independent.

The sickle cell patient, whose medical journey has been chronicled by NPR, achieved 11.3 g/dL of hemogobin 47% fetal at four months. While she experienced seven vaso-occlusive crises annually in the two years prior to treatment, the individual has yet to have one of the characteristic pain crises since CTX001 infusion.

"The ratio [between sickling, anti-sickling cells] is what matters in sickle cell to prevent sickle cell formation," said CRISPR's Kulkarni, noting that the study's main goal is the proportion of patients whose levels of fetal hemoglobin surpass 20%.

Both patients experienced serious side effects, albeit ones judged by investigators to be unrelated to treatment.

The first experienced pneumonia in the presence of neutropenia and veno-occlusiveliver disease that was linked to the chemotherapy pre-conditioning given before infusion of the gene-edited stem cells.The other reported sepsis occurring alongside neutropenia, gallstones and abdominal pain.

All events resolved, Vertex and CRISPR said.

Both the beta-thalassemia and sickle cell studies began last fall and are each set to enroll as many as 45 patients across sites in the U.S., Canada and Europe.

Enrollment and treatment have proceeded slowly, allowing for the companies to carefully monitor patient safety. The Food and Drug Administration, which previously placed a since-lifted clinical hold on CTX001 in sickle cell disease, has also taken a cautious view of gene-editing therapies.

Once CRISPR and Vertex treat two patients in each study, they anticipate moving more quickly. Further data will be presented at a medical meeting next year, Kulkarni said.

Sickle cell and beta-thalassemia are caused by mutations in the beta-globin gene, leading to the characteristic sickled red blood cells in the former condition and dysfunctional cells in the latter. Anemia, or the resulting insufficient oxygen levels in the blood, can cause organ damage and shorten patients' lifespans.

Both are well understood genetic diseases and now a common target for drugmakershoping to apply advances in gene replacement and gene editing medicine.Biotech developer Bluebird bio, for example, recently won approval in Europe for the gene therapy Zyntegloto treat transfusion-dependent beta-thalassemia, and it hopes to soon expand into sickle cell as well.

Besides Vertex and CRISPR, other drugmakers are advancing CRISPR-based medicines. Editas Medicine, which licenses its intellectual property from a rival academic camp to CRISPR Therapeutics, plans to treat the first patient in a study of its gene-editing candidate for a rare eye disease early next year. A third company, Intellia Therapeutics, is further behind.

Gene editing efforts in academia are progressing, too. Researchers from the University of Pennsylvania recently reported initial findings from the first attempt in the U.S. to use CRISPR gene editing to treat cancer, while in China scientists have moved quickly ahead with testing CRISPR in humans.

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First look at CRISPR, Vertex gene-editing therapy hints at treatment potential - BioPharma Dive

Binding of steroid estrogen hormones to estrogen receptor (ER) in the cell nucleus triggers the sequential recruitment different coactivators to regulate gene transcription.

Estrogen hormones regulate gene expression. They achieve this by first binding to estrogen receptor in the cell nucleus, which triggers the recruitment of different molecules called coactivators in specific order. In a study published in Molecular Cell, a team of researchers at Baylor College of Medicine, the University of Texas MD Anderson Cancer Center and the University of Texas Health Science Center at Houston shows that the sequential recruitment of coactivators is not simply adding molecules to the complex, it results in dynamic specific structural and functional changes that are necessary for effective regulation of gene expression.

Estrogens are a group of hormones that are essential for normal female sexual development and for the healthy functioning of the reproductive system. They also are involved in certain conditions, such as breast cancer. Estrogen also plays a role in male sexual function. Estrogens carry out their functions by turning genes on and off via a multi-step process. After estrogen binds to its receptor, different coactivators bind to the complex in a sequential manner.

Experimental evidence suggests that different estrogen-receptor coactivators communicate and cooperate with each other to regulate gene expression, said corresponding author Dr. Bert OMalley, chair and professor of molecular and cellular biology and Thomas C. Thompson Chair in Cell Biology at Baylor College of Medicine. However, how this communication takes place and how it guides the sequence of events that regulate gene expression was not clear.

In this study, OMalley, Dr. Wah Chiu, Distinguished Service Professor and Alvin Romansky Professor of Biochemistry and Molecular Biology at Baylor during the development of this project, and their colleagues combined cryo-electron microscopy structure analysis and biochemical techniques and showed how the recruitment of a specific coactivator CARM1 into the complex guides the subsequent steps leading to gene activation.

For the estrogen receptor complex to be able to regulate gene expression, the coactivator CARM1 needs to be added after other coactivators have been incorporated into the complex, said first author Dr. Ping Yi, assistant professor of molecular and cellular biology at Baylor. We discovered that when CARM1 is added, it changes the complex both chemically and structurally, and these changes guide subsequent steps that lead to gene activation.

We now have a better understanding of how this molecular machine works and of what role each one of the components plays. We are better prepared to understand what might have gone wrong when the machine fails, OMalley said.

Other contributors to this work include Zhao Wang, Qin Feng, Chao-Kai Chou, Grigore D. Pintilie, Hong Shen, Charles E. Foulds, Guizhen Fan, Irina Serysheva, Steven J. Ludtke, Michael F. Schmid, Mien-Chie Hung and Wah Chiu.

Support for this study was provided by the Komen Foundation (5PG12221410), the Department of Defense (R038318-I and W81XWH-15-1-0536); National institutes of Health grants (HD8818, NIDDK59820, P41GM103832 and R01GM079429); CNIHR, R21AI122418 and R01GMGM072804; CPRIT grants (RP150648 and DP150052); and a National Cancer Institute Cancer Center Support grant (P30CA125123) to the BCM Monoclonal Antibody/recombinant Protein Expression Core Facility.

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Research reveals how estrogen regulates gene expression - Baylor College of Medicine News (press release)