Genomics  

A new 'Grand Challenge' project with George Church and Andrew Hessel among the leadership team has been announced that will effectively take the learnings from the Human Genome Project to create an engineered version of human genetic code. 

A group of scientific, business and policy leaders have announced their intention to launch The Genome Project-write (HGP-write) this year.

The project will be an open, international research project led by a multi-disciplinary group of scientific leaders who will oversee a reduction in the costs of engineering and testing large genomes, including a human genome, in cell lines more than 1,000-fold within ten years.

The overarching goal of this effort is to understand the blueprint of life provided by the Human Genome Project (HGP-read).

According to the project materials, our understanding of the human genome – and the full benefits to humanity to be obtained from this knowledge — remains far from complete. Project scientists now believe that to truly understand our genetic blueprint, it is necessary to “write” DNA and build human (and other) genomes from scratch. Such an endeavor will require research and development on a grand scale.

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"Exponential improvements in genome engineering technologies and functional testing provide an opportunity to deepen the understanding of our genetic blueprint and use this knowledge to address many of the global problems facing humanity."

As detailed in the journal Science, the goal is to launch HGP-write in 2016 with $100 million in committed support from public, private, philanthropic, industry, and academic sources globally. The project will be implemented through a new, independent nonprofit organization, the Center of Excellence for Engineering Biology.

HGP-write will build on the knowledge gained by The Human Genome Project (HGP-read), biology's first large-scale project that has sparked scientific and medical transformation, especially in genomic-based discovery, diagnostics, and therapeutics. Whereas HGP-read "read" DNA to understand its code, HGP-write will use the cellular machinery provided by nature to "write" code, constructing vast DNA chains.

According to the authors of the Science commentary, although "...sequencing, analyzing and editing DNA continues to advance at breakneck pace, the capability to construct DNA sequences in cells is mostly limited to a small number of short segments, restricting the ability to manipulate and understand biological systems."

The new effort is expected to lead to a massive amount of information connecting the sequence of nucleotide bases in DNA with their physiological properties and functions. As a result, HGP-write promises to have a significant impact on human health and other critical areas such as energy, agriculture, chemicals, and regenerative medicine.

HGP-write will be an open, international, multi-disciplinary research project with the following leadership team:

• Jef Boeke, Ph.D., Director, Institute for Systems Genetics, Professor, Department of Biochemistry and Molecular Pharmacology, NYU Langone Medical Center. Dr. Boeke is a leader of the Synthetic Yeast Project (Sc2.0), which seeks to create living yeast cells with entirely redesigned chromosomes by 2017.

• George Church, Ph.D., Robert Winthrop Professor of Genetics at Harvard Medical School, Core Faculty Member at the Wyss Institute for Biologically Inspired Engineering at Harvard University, Professor of Health Sciences and Technology at Harvard and the Massachusetts Institute of Technology (MIT), and Senior Associate Faculty member at the Broad Institute. Among the leaders of the original HGP-read, Dr. Church currently heads an effort to create a version of the bacteria E.coli with a redesigned genome.

• Andrew Hessel, Distinguished Researcher, Bio/Nano Research Group, Autodesk. He spearheads a multidisciplinary team exploring computer-aided design and manufacturing for biotechnology and nanotechnology R&D.

• Nancy J Kelley, J.D., M.P.P., President & CEO, Nancy J Kelley & Associates, formerly Founding Executive Director, New York Genome Center. She is lead executive of HGP-write and the related Center of Excellence for Engineering Biology.

"This grand challenge is more ambitious and more focused on understanding the practical applications than the original Human Genome Project, which aimed to 'read' a human genome," said Church. "Exponential improvements in genome engineering technologies and functional testing provide an opportunity to deepen the understanding of our genetic blueprint and use this knowledge to address many of the global problems facing humanity."

Another proposed benefit of the project is the development of new genomics analysis, design, synthesis, assembly and testing technologies, with the goal of making them more affordable and widely available. "Writing DNA code is the future of science and medicine, but our technical capabilities remain limited," said Hessel. "HGP-write will require research and development on a grand scale, and this effort will help to push our current technical limits by several orders of magnitude."

"The overarching goal of such an effort is to understand the blueprint for life provided by the Human Genome Project (HGP-read)."

"Initially, our efforts will focus on synthesizing about 1% of the human genome to evaluate feasibility and value, just as was done for the HGP-read and just as we did for the Synthetic Yeast Genome Project, or Sc2.0," said Boeke. "The difference is that these 1% pilot projects will not be random; instead, they will be selected based on their ability to provide early-stage resources for biomedical research and development."

The Center of Excellence for Engineering Biology will coordinate and support the formation and work of multi-institutional and interdisciplinary research teams working in a highly integrated fashion, responsive to and engaged with a broad public outreach. Additional Centers could be included in the future.

Some applications that may arise from HGP-write that could have a significant impact on human health and lifespan longevity include, but are not limited to:

• Growing transplantable human organs, thus saving the lives of thousands of patients globally who die waiting for donated organs from those who die from disease or accidents

• Engineering immunity to viruses in cell lines

• Engineering cancer resistance into new therapeutic cell lines

• Enabling high-productivity, cost-efficient vaccine and pharmaceutical development using human cells and organoids that makes precision medicine more affordable and universal

"The Center will help to strengthen and support the efforts of the national and international communities on this endeavor," said Kelley. "But more importantly, the Center will represent a visible, stable, accountable and long-term commitment to advancing the field of engineering biology in the public interest."

This project developed from a series of meetings held over the last several years, including a meeting held at NYU Langone Medical Center on October 31, 2015. The latest meeting, held on May 10 in Boston, brought together a diverse group of 130 participants from many different countries, including biologists, ethicists, engineers, plus representatives from industry, law and government to discuss the next chapter in our understanding of the blueprint of life. A video of that meeting will soon be posted on http://www.hgpwrite.org.

What is your opinion of the HGP-write project? Is it just a contemporary type of eugenics? Will it lead to the engineering of future threats like Khan Noonien Singh in Star Trek?

The average human lifespan continues to expand as a result of advancements in science, medicine, and public health. The challenge today lies in living extended, healthy lives with minimal burden of disease – and the associated costs to society. The HGP-write project may grow to be a big factor in taking on this challenge.

SOURCE  PR Newswire

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Videos  

Geneticist, biologist and molecular engineer George Church has cracked the genome, so Stephen Colbert is pretty sure that means we're all going to live forever.

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SOURCE  The Late Show with Stephen Colbert

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 Genetic Engineering  

Two parallel projects at Harvard’s Wyss Institute have created new genomes inside the bacterium E. coli in ways that test the limits of genetic reprogramming and open new possibilities for increasing flexibility, productivity. and safety in biotechnology.

In two parallel projects, researchers have created new genomes inside the bacterium E. coli in ways that test the limits of genetic reprogramming, opening new possibilities for increasing flexibility, productivity and safety in biotechnology.

In one project, researchers created a novel genome—the first-ever entirely genomically recoded organism—by replacing all 321 instances of a specific “genetic three-letter word,” called a codon, throughout the organism’s entire genome with a word of supposedly identical meaning. The researchers then reintroduced a reprogrammed version of the original word (with a new meaning, a new amino acid) into the bacteria, expanding the bacterium’s vocabulary and allowing it to produce proteins that do not normally occur in nature.

In the second project, the researchers removed every occurrence of 13 different codons across 42 separate E. coli genes, using a different organism for each gene, and replaced them with other codons of the same function. When they were done, 24 percent of the DNA across the 42 targeted genes had been changed, yet the proteins the genes produced remained identical to those produced by the original genes.

“The first project is saying that we can take one codon, completely remove it from the genome, then successfully reassign its function,” said Marc Lajoie, a Harvard Medical School graduate student in the lab of George Church. “For the second project we asked, ‘OK, we've changed this one codon, how many others can we change?’”

Of the 13 codons chosen for the project, all could be changed.

“That leaves open the possibility that we could potentially replace any or all of those 13 codons throughout the entire genome,” Lajoie said.

The results of these two projects appearred recently in the journal Science. The work was led by Church, Robert Winthrop Professor of Genetics at Harvard Medical School and founding core faculty member at the Wyss Institute for Biologically Inspired Engineering. Farren Isaacs, assistant professor of molecular, cellular, and developmental biology at Yale School of Medicine, is co-senior author on the first study.

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Recoded genomes can confer protection against viruses—which limit productivity in the biotech industry—and help prevent the spread of potentially dangerous genetically engineered traits to wild organisms.

“In science we talk a lot about the ‘what’ and the ‘how’ of things, but in this case, the ‘why’ is very important,” Church, author of Regenesis: How Synthetic Biology Will Reinvent Nature and Ourselves said, explaining how this project is part of an ongoing effort to improve the safety, productivity and flexibility of biotechnology.

“These results might also open a whole new chemical toolbox for biotech production,” said Isaacs. “For example, adding durable polymers to a therapeutic molecule could allow it to function longer in the human bloodstream.”

But to have such an impact, the researchers said, large swaths of the genome need to be changed all at once.

“If we make a few changes that make the microbe a little more resistant to a virus, the virus is going to compensate. It becomes a back and forth battle,” Church said. “But if we take the microbe offline and make a whole bunch of changes, when we bring it back and show it to the virus, the virus is going to say ‘I give up.’ No amount of diversity in any reasonable natural virus population is going to be enough to compensate for this wildly new genome.”

In the first study, with just a single codon removed, the genomically recoded organism showed increased resistance to viral infection. With several additional codons reassigned, a “wildly new genome” would make it impossible for engineered genes to escape into wild populations, Church said, because they would be incompatible with natural genomes. This could be of considerable benefit with strains engineered for drug or pesticide resistance, for example. What’s more, incorporating rare, non-standard amino acids could ensure strains only survive in a laboratory environment.

Since a single genetic flaw can spell death for an organism, the challenge of managing a series of hundreds of specific changes was daunting, the researchers said. In both projects, the researchers paid particular attention to developing a methodical approach to planning and implementing changes and troubleshooting the results.

“We wanted to develop the ability to efficiently build the desired genome and to very quickly identify any problems—from design flaws or from undesired mutations — and develop workarounds,” Lajoie said.

The team relied on number of technologies developed in the Church lab and the Wyss Institute and with partners in academia and industry, including next-generation sequencing tools, DNA synthesis on a chip, and MAGE and CAGE genome editing methods. But one of the most important tools they used was the power of natural selection, the researchers added.

“When an engineering team designs a new cellphone, it’s a huge investment of time and money. They really want that cell phone to work,” Church said. “With E. coli we can make a few billion prototypes with many different genomes, and let the best strain win. That’s the awesome power of evolution.”



SOURCE  Harvard Medical School

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 Neuroscience  

The New York Times has reported that the Obama administration is planning a decade-long scientific effort to examine the workings of the human brain and build a comprehensive map of its activity, seeking to do for the brain what the Human Genome Project did for genetics. The project, which the administration has been looking to unveil as early as March, will include federal agencies, private foundations, and teams of neuroscientists and nanoscientists in a concerted effort to advance the knowledge of the brain’s billions of neurons and gain greater insights into perception, actions and, ultimately, consciousness.

A ccording to the New York Times, the Obama administration is now planning a decade-long scientific effort to examine the workings of the human brain and build a comprehensive map of its activity, seeking to do for the brain what the Human Genome Project did for genetics.

President Obama hinted that he wanted the United States to reestablish the importance of science and technology in his recent State of the Union address:

Every dollar we invested to map the human genome returned $140 to our economy. Today, our scientists are mapping the human brain to unlock the answers to Alzheimer’s; developing drugs to regenerate damaged organs; devising new material to make batteries ten times more powerful. Now is not the time to gut these job-creating investments in science and innovation. Now is the time to reach a level of research and development not seen since the height of the Space Race.

While Obama went on to talk about energy, the European Union's funding of Henry Markram's Human Brain Project and other large neuroscience research efforts clearly offer a Space Race-type framework for the US to center its science goals around.

After the speech, Francis S. Collins, the director of the National Institutes of Health, may have inadvertently confirmed the plan when he wrote in a Twitter message: “Obama mentions the #NIH Brain Activity Map in #SOTU.”

The administration looks to unveil the project as early as March, will include federal agencies, private foundations and teams of neuroscientists and nanoscientists in a concerted effort to advance the knowledge of the brain’s billions of neurons and gain greater insights into perception, actions and, ultimately, consciousness.

The potential economic impacts of the effort could be huge.  Impacting all areas of imaging, medicine, computing and the development of artificial intelligence, understanding the human brain has now been  recognized by countries as an ambition worthy of throwing the weight of the US government behind it.

Scientists with the highest hopes for the project also see it as a way to develop the technology essential to understanding diseases like Alzheimer’s and Parkinson’s, as well as to find new therapies for a variety of mental illnesses.

Understanding the brain has extensive implications for Singularity aims as well.  Brain-machine and brain-to-brain interfaces will require a much greater understanding of the neurological connections within us.  Also, an ultimate definition of the biological underpinnings of consciousness may increase the possibility for uploading brains to non-biological substrates.

The project, which could ultimately cost billions of dollars, is expected to be part of the president’s budget proposal next month. And, four scientists and representatives of research institutions said they had participated in planning for what is being called the Brain Activity Map project.

The details are not final, and it is not clear how much federal money would be proposed or approved for the project in a time of fiscal constraint or how far the research would be able to get without significant federal financing.

The project could provide a lift for the economy. “The Human Genome Project was on the order of about $300 million a year for a decade,” said George M. Church, a Harvard University molecular biologist who helped create that project and said he was helping to plan the Brain Activity Map project. “If you look at the total spending in neuroscience and nanoscience that might be relative to this today, we are already spending more than that. We probably won’t spend less money, but we will probably get a lot more bang for the buck.”

The advent of new technology that allows scientists to identify firing neurons in the brain has led to numerous brain research projects around the world. Yet the brain remains one of the greatest scientific mysteries.

Composed of roughly 100 billion neurons that each electrically “spike” in response to outside stimuli, as well as in vast ensembles based on conscious and unconscious activity, the human brain is so complex that scientists have not yet found a way to record the activity of more than a small number of neurons at once, and in most cases that is done invasively with physical probes.

Nanotechnologists and neuroscientists say they believe that technologies are at hand to make it possible to observe and gain a more complete understanding of the brain, and to do it less intrusively.  These possibilities were outlined by Ray Kurzweil in his book, The Singularity Is Near

Mapping and understanding the human brain presented a drastically more significant challenge than mapping the genome.

“It’s different in that the nature of the question is a much more intricate question,” said Dr. Greenspan, who said he is involved in the brain project. “It was very easy to define what the genome project’s goal was. In this case, we have a more difficult and fascinating question of what are brainwide activity patterns and ultimately how do they make things happen?”

SOURCE  New York Times

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