Category Archives: Human Genetic Engineering

Should scientists be allowed to create extremely aggressive and highly infectious influenza viruses? Dutch virologists have done it and, in the process, triggered a fierce debate over the risks of bioterrorism and the potential release of deadly viruses.

The 17th floor of the Erasmus Medical Center in the Dutch city of Rotterdam certainly doesn't look like the kind of place that could pose a threat to global security. A disco ball hangs from the ceiling in the hallway in front of the elevators, and a bar with a golden beer tap stands in the corner of the conference room.

Everything in this 1960s high-rise building evokes the charm of student life, including the door to Room 17.73, which is covered with colorful stickers. But some view the scientist who sits behind that door as a threat to mankind.

Ron Fouchier, a giant of a man at more than two meters tall (6'6"), has dark circles under his eyes. His life has been stressful lately. "They want to paint me as a homicidal idiot," he says heatedly. He is referring, most of all, to a powerful institution from the United States, the National Science Advisory Board for Biosecurity (NSABB).

In his work Fouchier, a virologist, uses the methods of a branch of research that is as booming as it is controversial. Synthetic biology employs targeted manipulation through genetic engineering to construct new organisms. The 45-year-old's research has even set off alarm bells at the World Health Organization (WHO). This week, Fouchier will appear before an international panel of experts at the WHO to explain his experiments.

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Fouchier is attracting so much attention because he has created a new organism. And although it is tiny, if it escaped from his laboratory it would claim far more human lives than an exploding nuclear power plant.

The pathogen is a new mutation of the feared bird flu virus, H5N1. In nature, this virus, which kills one of every two people infected, has not yet been transmitted from humans to humans. So far, a relatively small number of people have caught the virus from poultry, and 336 people have died.

Scientific Wake-Up Call

For years, experts feared that the adaptable virus could soon mutate from being primarily a bird killer to a highly infectious threat to humans. But as the years passed and this did not happen, many hoped that it might not even be possible, and some of the fears subsided.

But now Fouchier's experiments have given the research community a wake-up call. The scientist performed only a few targeted manipulations on the genetic material of the ordinary H5N1 virus and, to make the virus even more dangerous, he repeatedly transmitted it from one laboratory animal to the next.

"In the end, the virus became airborne," the Dutch scientist explains. From then on Fouchier's ferrets, animals that most closely resemble humans when it comes to influenza, transmitted the virus to each other without direct contact, through tiny droplets of saliva and mucus.

Many scientists are particularly impressed by the fact that, at almost the same time, another research team also managed to produce a bird flu virus that could be transmitted via airborne respiratory droplets. To achieve this, virologist Yoshihiro Kawaoka of the University of Wisconsin combined the avian flu virus with the swine flu virus. The newly created superbug is highly infectious, however not particularly dangerous to the ferrets Kawaoka used in his experiments.

Excerpt from:
Killer Virus Creation Spurs Debate

SAN DIEGO — Understanding how RNA binding proteins control the genetic splicing code is fundamental to human biology and disease — much like editing film can change a movie scene. Abnormal variations in splicing are often implicated in cancer and genetic neurodegenerative disorders.

In a step toward deciphering the "splicing code" of the human genome, researchers at the University of California, San Diego School of Medicine have comprehensively analyzed six of the more highly expressed RNA binding proteins collectively known as heterogeneous nuclear ribonucleoparticle (hnRNP) proteins.

This study, published online today (Feb. 16) in Cell Press' new open-access journal Cell Reports, describes how multiple RNA binding proteins cooperatively control the diversity of proteins in human cells by regulating the alternative splicing of thousands of genes.

In the splicing process, fragments that do not typically code for protein, called introns, are removed from gene transcripts, and the remaining sequences, called exons, are reconnected. The proteins that bind to RNA are important for the control of the splicing process, and the location where they bind dictates which pieces of the RNA are included or excluded in the final gene transcript — in much the same fashion that removing and inserting scenes, or splicing, can alter the plot of a movie.

"By integrating vast amounts of information about these key binding proteins, and making this data widely available, we hope to provide a foundation for building predictive models for splicing and future studies in other cell types such as embryonic stem cells," said principal investigator Gene Yeo, assistant professor in the Department of Cellular and Molecular Medicine and the Institute for Genomic Medicine at UC San Diego, and a visiting professor at the Molecular Engineering Laboratory in Singapore. "If we can understand how these proteins work together and affect one another to regulate alternative splicing, it may offer important clues for rational drug design."

The data sets highlighted in this study — derived from genome-wide methods including custom-designed splicing-sensitive microarrays, RNA sequencing and high-throughput sequencing to identify genome-wide binding sites (CLIP-seq) — map the functional binding sites for six of the major hnRNP proteins in human cells.

"We identified thousands of binding sites and altered splicing events for these hnRNP proteins and discovered that, surprisingly these proteins bind and regulate each other and a whole network of other RNA binding proteins, suggesting that these proteins are important for the homeostasis of the cell," said first author, NSF fellow Stephanie C. Huelga.

According to the UC San Diego researchers, the genes specifically targeted by the RNA binding proteins in this study are also often implicated in cancer. Yeo added that of the thousands of genomic mutations that appear in cancer, a vast majority occur in the introns that are removed during splicing; however, intronic regions are where regulatory hnRNP proteins often bind.

"Our findings show an unprecedented degree of complexity and compensatory relationships among hnRNP proteins and their splicing targets that likely confer robustness to cells. The orchestration of RNA binding proteins is not only important for the homeostasis of the cell, but — by mapping the location of binding sites and all the regulatory places in a gene — this study could reveal how disruption of the process leads to disease and, perhaps, a way to intervene."

Additional contributors to the study include Anthony Q. Vu, Justin D. Arnold, Tiffany Y. Liang, Patrick P. Liu and Bernice Y. Yan, UC San Diego Cellular and Molecular Medicine; John Paul Donohue, Lily Shiue and Manuel Ares, Jr., UC Santa Cruz; Shawn Hoon and Sydney Brenner, A*STAR, Singapore.

The study was funded in part by grants from the National Institutes of Health and the UC San Diego Stem Cell Research Program.

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Proteins cooperate to regulate gene splicing

ScienceDaily (Feb. 16, 2012) — Understanding how RNA binding proteins control the genetic splicing code is fundamental to human biology and disease -- much like editing film can change a movie scene. Abnormal variations in splicing are often implicated in cancer and genetic neurodegenerative disorders.

In a step toward deciphering the "splicing code" of the human genome, researchers at the University of California, San Diego School of Medicine have comprehensively analyzed six of the more highly expressed RNA binding proteins collectively known as heterogeneous nuclear ribonucleoparticle (hnRNP) proteins.

This study, published online Feb 16 in Cell Press' new open-access journal Cell Reports, describes how multiple RNA binding proteins cooperatively control the diversity of proteins in human cells by regulating the alternative splicing of thousands of genes.

In the splicing process, fragments that do not typically code for protein, called introns, are removed from gene transcripts, and the remaining sequences, called exons, are reconnected. The proteins that bind to RNA are important for the control of the splicing process, and the location where they bind dictates which pieces of the RNA are included or excluded in the final gene transcript -- in much the same fashion that removing and inserting scenes, or splicing, can alter the plot of a movie.

"By integrating vast amounts of information about these key binding proteins, and making this data widely available, we hope to provide a foundation for building predictive models for splicing and future studies in other cell types such as embryonic stem cells," said principal investigator Gene Yeo, PhD, assistant professor in the Department of Cellular and Molecular Medicine and the Institute for Genomic Medicine at UC San Diego, and a visiting professor at the Molecular Engineering Laboratory in Singapore. "If we can understand how these proteins work together and affect one another to regulate alternative splicing, it may offer important clues for rational drug design."

The data sets highlighted in this study -- derived from genome-wide methods including custom-designed splicing-sensitive microarrays, RNA sequencing and high-throughput sequencing to identify genome-wide binding sites (CLIP-seq) -- map the functional binding sites for six of the major hnRNP proteins in human cells.

"We identified thousands of binding sites and altered splicing events for these hnRNP proteins and discovered that, surprisingly these proteins bind and regulate each other and a whole network of other RNA binding proteins, suggesting that these proteins are important for the homeostasis of the cell," said first author, NSF fellow Stephanie C. Huelga.

According to the UCSD researchers, the genes specifically targeted by the RNA binding proteins in this study are also often implicated in cancer. Yeo added that of the thousands of genomic mutations that appear in cancer, a vast majority occur in the introns that are removed during splicing; however, intronic regions are where regulatory hnRNP proteins often bind.

"Our findings show an unprecedented degree of complexity and compensatory relationships among hnRNP proteins and their splicing targets that likely confer robustness to cells. The orchestration of RNA binding proteins is not only important for the homeostasis of the cell, but -- by mapping the location of binding sites and all the regulatory places in a gene -- this study could reveal how disruption of the process leads to disease and, perhaps, a way to intervene."

Additional contributors to the study include Anthony Q. Vu, Justin D. Arnold, Tiffany Y. Liang, Patrick P. Liu and Bernice Y. Yan, UCSD Cellular and Molecular Medicine; John Paul Donohue, Lily Shiue and Manuel Ares, Jr., UC Santa Cruz; Shawn Hoon and Sydney Brenner, A*STAR, Singapore.

The study was funded in part by grants from the National Institutes of Health and the UC San Diego Stem Cell Research Program.

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The above story is reprinted from materials provided by University of California, San Diego Health Sciences, via Newswise.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Stephanie C. Huelga, Anthony Q. Vu, Justin D. Arnold, Tiffany Y. Liang, Patrick P. Liu, Bernice Y. Yan, John Paul Donohue, Lily Shiue, Shawn Hoon, Sydney Brenner, Manuel Ares, Gene W. Yeo. Integrative Genome-wide Analysis Reveals Cooperative Regulation of Alternative Splicing by hnRNP Proteins. Cell Reports, 2012; DOI: 10.1016/j.celrep.2012.02.001

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

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The splice of life: Proteins cooperate to regulate gene splicing

MONTREAL, Feb. 16, 2012 /CNW Telbec/ - Researchers at Polytechnique Montréal have succeeded in changing the genetic material of cancer cells using a brand-new transfection method. This major breakthrough in nanosurgery opens the door to new medical applications, among others for the treatment of cancers.

A light scalpel to treat cancerous cells

The unique method developed by Professor Michel Meunier and his team uses a femtosecond laser (a laser with ultra-short pulses) along with gold nanoparticles. Deposited on the cells, these nanoparticles concentrate the laser's energy and make it possible to perform nanometric-scale surgery in an extremely precise and non-invasive fashion. The technique allows to change the expression of genes in the cancer cells and could be used to slow their migration and prevent the formation of metastases.

The technique perfected by Professor Meunier and his colleagues is a promising alternative to conventional cellular transfection methods, such as lipofection. The experiment, carried out in Montréal laboratories on malignant human melanoma cells, demonstrated 70% optoporation effectiveness, as well as a transfection performance three times higher than lipofection treatment. In addition, unlike conventional treatment, which destroys the physical integrity of the cells, the new method assures cellular viability, with a toxicity of less than 1%. The study's results were published in the prestigious journal Biomaterials.

This major scientific breakthrough could lead to the development of promising applications, including new therapeutic approaches in oncology, neurology and cardiology.

Professor Meunier's team works in collaboration with researchers from the Department of Medicine at the McGill University Health Centre. Their research work receives financial support from the Fonds Québécois de la Recherche sur la Nature et les Technologies (FQRNT), the Canada Foundation for Innovation (CFI), the Canada Research Chairs program (CRC), the Canadian Institutes of Health Research (CIHR) and the Deutsche Forschungsgemeinschaft (DFG).

About Polytechnique Montreal

Founded in 1873, Polytechnique Montréal is one of Canada's leading engineering teaching and research institutions. It is the largest engineering university in Québec for the size of its student body and the scope of its research activities. With over 38,500 graduates, Polytechnique Montréal has graduated 25% of the current members of the l'Ordre des ingénieurs du Québec. Polytechnique provides training in 16 engineering specialties, has 242 professors and more than 7,100 students. It has an annual operating budget of over $200 million, including a $72-million research budget.

REFERENCE: Baumgart  J. et al., Off-resonance plasmonic enhanced femtosecond laser optoporation and transfection of cancer cells, Biomaterials (2012), doi:10.1016/j.biomaterials.2011.11.062

Annie Touchette
Senior Communications Advisor
Communications and Recruitment Office
Polytechnique Montréal
Tel.: 514 340-4711
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Cell: + 1 514 231-8133
annie.touchette@polymtl.ca

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Nanosurgery and the fight against cancer: major breakthrough at Polytechnique Montréal

The World Economic Forum's Global Agenda Council on Emerging Technologies has drawn up a list of the top 10 emerging technologies for 2012 (Image: Shutterstock)

Our goal here at Gizmag is to cover innovation and emerging technologies in all fields of human endeavor, and while almost all of the ideas that grace our pages have the potential to enhance some of our lives in one way or another, at the core are those technologies that will have profound implications for everyone on the planet. For those looking to shape political, business, and academic agendas, predicting how and when these types of technologies will effect us all is critical. Recognizing this, the World Economic Forum's (WEF's) Global Agenda Council on Emerging Technologies has compiled a list of the top 10 emerging technologies it believes will have the greatest impact on the state of the world in 2012.

Betting on the right technologies can allow schools to produce graduates better qualified to deal with a rapidly changing world, governments to more efficiently meet the needs of the populace, business to generate profits, and scientists to better allocate resources.

The list draws on some of the brainpower residing within the entire GAC Network, covering the top ten technological trends that the Global Agenda Council on Emerging Technologies believes will have the biggest social, economic and environmental impacts this year.

Here's the list as presented on the World Economic Forum Blog in order from lowest to highest in terms of the potential to provide solutions to global challenges.

1. Informatics for adding value to information The quantity of information now available to individuals and organizations is unprecedented in human history, and the rate of information generation continues to grow exponentially. Yet, the sheer volume of information is in danger of creating more noise than value, and as a result limiting its effective use. Innovations in how information is organized, mined and processed hold the key to filtering out the noise and using the growing wealth of global information to address emerging challenges. 2. Synthetic biology and metabolic engineering The natural world is a testament to the vast potential inherent in the genetic code at the core of all living organisms. Rapid advances in synthetic biology and metabolic engineering are allowing biologists and engineers to tap into this potential in unprecedented ways, enabling the development of new biological processes and organisms that are designed to serve specific purposes - whether converting biomass to chemicals, fuels and materials, producing new therapeutic drugs or protecting the body against harm. 3. Green Revolution 2.0 - technologies for increased food and biomass Artificial fertilizers are one of the main achievements of modern chemistry, enabling unprecedented increases in crop production yield. Yet, the growing global demand for healthy and nutritious food is threatening to outstrip energy, water and land resources. By integrating advances across the biological and physical sciences, the new green revolution holds the promise of further increasing crop production yields, minimizing environmental impact, reducing energy and water dependence, and decreasing the carbon footprint. 4. Nanoscale design of materials The increasing demand on natural resources requires unprecedented gains in efficiency. Nanostructured materials with tailored properties, designed and engineered at the molecular scale, are already showing novel and unique features that will usher in the next clean energy revolution, reduce our dependence on depleting natural resources, and increase atom-efficiency manufacturing and processing. 5. Systems biology and computational modelling/simulation of chemical and biological systems For improved healthcare and bio-based manufacturing, it is essential to understand how biology and chemistry work together. Systems biology and computational modeling and simulation are playing increasingly important roles in designing therapeutics, materials and processes that are highly efficient in achieving their design goals, while minimally impacting on human health and the environment. 6. Utilization of carbon dioxide as a resource Carbon is at the heart of all life on earth. Yet, managing carbon dioxide releases is one of the greatest social, political and economic challenges of our time. An emerging innovative approach to carbon dioxide management involves transforming it from a liability to a resource. Novel catalysts, based on nanostructured materials, can potentially transform carbon dioxide to high value hydrocarbons and other carbon-containing molecules, which could be used as new building blocks for the chemical industry as cleaner and more sustainable alternatives to petrochemicals. 7. Wireless power Society is deeply reliant on electrically powered devices. Yet, a significant limitation in their continued development and utility is the need to be attached to the electricity grid by wire - either permanently or through frequent battery recharging. Emerging approaches to wireless power transmission will free electrical devices from having to be physically plugged in, and are poised to have as significant an impact on personal electronics as Wi-Fi had on Internet use. 8. High energy density power systems Better batteries are essential if the next generation of clean energy technologies are to be realized. A number of emerging technologies are coming together to lay the foundation for advanced electrical energy storage and use, including the development of nanostructured electrodes, solid electrolysis and rapid-power delivery from novel supercapacitors based on carbon-based nanomaterials. These technologies will provide the energy density and power needed to supercharge the next generation of clean energy technologies. 9. Personalized medicine, nutrition and disease prevention As the global population exceeds 7 billion people - all hoping for a long and healthy life - conventional approaches to ensuring good health are becoming less and less tenable, spurred on by growing demands, dwindling resources and increasing costs. Advances in areas such as genomics, proteomics and metabolomics are now opening up the possibility of tailoring medicine, nutrition and disease prevention to the individual. Together with emerging technologies like synthetic biology and nanotechnology, they are laying the foundation for a revolution in healthcare and well-being that will be less resource intensive and more targeted to individual needs. 10. Enhanced education technology New approaches are needed to meet the challenge of educating a growing young population and providing the skills that are essential to the knowledge economy. This is especially the case in today's rapidly evolving and hyperconnected globalized society. Personalized IT-based approaches to education are emerging that allow learner-centerd education, critical thinking development and creativity. Rapid developments in social media, open courseware and ubiquitous access to the Internet are facilitating outside classroom and continuous education.

We know there's nothing like a list of predictions to provoke some healthy debate, so let us know what you think of the GAC on Emerging Technologies' effort in the comments. Is there anything you think they've overlooked, or maybe something they've included that shouldn't be there?

Source: World Economic Forum Blog

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World Economic Forum lists top 10 emerging technologies for 2012

ANN ARBOR — The University of Michigan’s first human embryonic stem cell line will be placed on the U.S. National Institutes of Health’s registry, making the cells available for federally funded research. It is the first of the stem cell lines derived at the University of Michigan to be placed on the registry.

The line, known as UM4-6, is a genetically normal line, derived in October 2010 from a cluster of about 30 cells removed from a donated five-day-old embryo roughly the size of the period at the end of this sentence. That embryo was created for reproduction through in-vitro fertilization but was no longer needed for that purpose and was therefore about to be discarded.

“This is significant, because acceptance of these cells on the registry demonstrates our attention to details of proper oversight, consenting, and following of NIH guidelines established in 2009,” says Gary Smith, who derived the line and also is co-director of the U-M Consortium for Stem Cell Therapies, part of the A. Alfred Taubman Medical Research Institute. “It now makes the line available to researchers who can apply for federal funding to use it in their work; this is an important step.”

The line is the culmination of years of planning and preparation and was made possible by Michigan voters’ November 2008 approval of a state constitutional amendment permitting scientists here to derive embryonic stem cell lines using surplus embryos from fertility clinics or embryos with genetic abnormalities and not suitable for implantation.

“We expect these cells will be used by investigators worldwide to enhance our understanding of stem cell biology, and together with disease-specific lines, discover treatments and cures for genetic diseases,” says Smith, who is a professor in the Department of Obstetrics and Gynecology at the University of Michigan Medical School.

UM is among just a handful of United States universities creating human embryonic stem cell lines. There are only 147 stem cell lines available on the registry.

“We envision in the future that investigators will be able to use the genetically normal embryonic stem cell lines like UM4-6, together with disease-specific embryonic stem cell lines, as a model system to investigate what causes these diseases and come up with treatments,” said Sue O’Shea, professor of Cell and Developmental Biology, and co-director of the Consortium for Stem Cell Therapies.

UM also has two other human embryonic stem cells lines submitted to the national registry. Both are disease specific, the first carrying the genetic defect that causes hemophilia B, and the other carries the gene responsible for Charcot-Marie-Tooth disease, a hereditary neurological disorder.

Smith expects to soon submit eight additional human embryonic stem lines for consideration on the national registry: three genetically normal and five new disease specific lines.

This is a historic achievement that will lead to treatments and cures for serious, life-altering diseases and is more evidence that our University of Michigan researchers are leading the world in cutting-edge science that will impact health around the globe, says Eva Feldman, M.D., director of the A. Alfred Taubman Medical Research Institute.

“This is another major step forward for medical science in Michigan,” Feldman said. “This opens us another avenue for researchers to really begin exploring the causes and progression of those diseases, with the ultimate goal of finding new therapies for patients.”

Contributors to the A. Alfred Taubman Medical Research Institute’s Consortium for Stem Cell Therapies include the Taubman Institute; the Office of the Executive Vice President for Medical Affairs; the Office of the Medical School Dean; the Comprehensive Cancer Center; the Department of Pediatrics and Communicable Diseases; the Office of the Vice President for Research; the School of Dentistry; the Department of Pathology; the Department of Cell and Developmental Biology; the College of Engineering; the Life Sciences Institute; the Department of Neurology; and U-M’s Michigan Institute for Clinical and Health Research.

A. Alfred Taubman, founder and chair of UM’s Taubman Institute, called the registry placement a tremendous step for stem cell research.

“I consider stem cells to be a modern medical miracle – the most exciting advance in medicine since antibiotics. The progress we have made throughout the state in stem cell research has been nothing short of remarkable,” Taubman said. “This milestone means much to the University of Michigan and the state of Michigan, but also to the world. It offers another route for researchers to move ahead in studying these horrible diseases. We hope it is the first of many lines that the University of Michigan can contribute to the global efforts to improve human health.”

For more information about the A. Alfred Taubman Medical Research Institute at the University of Michigan Medical School, visit http://www.taubmaninstitute.org

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UM Human Embryonic Stem Cell Line Placed On National Registry