Institute for Systems Genetics
Institute for Systems Genetics
News Article | May 10, 2017
New York, NY - The Center for Excellence in Engineering Biology today announced funding for a pilot study entitled "Engineering Prototrophy in Mammalian Cells," which will aim to generate versions of human cells that can grow with significantly reduced external nutrients (e.g. 'prototrophic'). The support comes through a grant of approximately $500,000 awarded to Columbia University by the Defense Advanced Research Projects Agency (DARPA). The objective of the pilot project is to generate human cells that can produce metabolites - small molecules needed for growth. Longer-term, the study could help generate new information about the biochemical environment needed for mammalian development, cell differentiation, and nutrition-associated aging processes. Information from the project may also lead to more efficient methods of synthesizing drugs and biologics produced in mammalian cell lines. The principal investigators of the funded project are Harris Wang, Ph.D., Assistant Professor, Department of Systems Biology at Columbia University, and Jef D. Boeke, Ph.D., Director, Institute for Systems Genetics, Professor, Department of Biochemistry and Molecular Pharmacology, NYU Langone Medical Center. This project is the first of several anticipated pilot projects currently seeking support as part of the Genome Project-write (GP-write) Grand Challenge, a multi-center, international technology initiative focused on DNA synthesis and the engineering of metabolic pathways, led by a multi-disciplinary group of scientific leaders and coordinated by the Center for Excellence in Engineering Biology. "It's really amazing to think we can see what happens if we restore to mammalian cells grown in dishes signaling pathways that were lost millions of years ago in evolution," said Boeke. He added, "I believe this is an example of genome engineering in human cells that will not only generate new knowledge, but may help us solve a practical problem in biotechnology." "By engineering mammalian metabolism, we will not only learn about how cells use nutrients to grow, but also how those processes, when they go awry, can contribute to diseases such as cancer," said Wang. "It's exciting to embark on this pilot project as a part of the GP-write Grand Challenge. I'm look forward to working with many others in this global effort," he added. GP-write, which has no direct affiliation with DARPA, will focus on using synthesis and genome editing technologies to understand, engineer and test model organisms as well as less tractable human and plant cell lines. The goal of GP-write is not only to deepen an understanding of life but to develop pragmatic technology of general use in biology, improving the cost and quality of DNA synthesis, and DNA assembly in cells. Planning for GP-write has been underway for the past three years, through a series of meetings of scientists, culminating in a Science publication in June 2016 and a white paper in November 2016. The funding announcement was made at a meeting of GP-write held this week at the New York Genome Center in New York City. The meeting agenda included discussions about roadmaps for the project, including scientific direction, technology development, ethical, social and legal engagement, standards and infrastructure development, amongst others. Scientific topics included the introduction and discussion of new Pilot Projects and the creation of an Industry Consortium. GP-write will be implemented through the Center of Excellence for Engineering Biology, a new, independent nonprofit organization that will manage planning and coordination efforts. These efforts include supporting 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. Nancy J Kelley, J.D., M.P.P., is the lead executive of GP-write and the Center of Excellence for Engineering Biology.
News Article | May 2, 2017
Last May a seemingly commonplace meeting kicked off a firestorm of controversy. More than 100 experts in genetics and bioengineering convened at Harvard Medical School for a meeting that was closed to the public — attendees were asked not to contact news media or to post about the meeting on social media. The same group is getting back together in New York City next week. To the meeting organizers, last year's secretive measures were, counterintuitively, to make sure as many people heard about the project as possible. They were submitting a paper about the project to a scientific journal and were discouraged from sharing the information publicly before it was published. But there's another reason why this group of scientists, while encouraging debate and public involvement, would be wary of attracting too much attention. Their project is an effort to synthesize DNA, including human DNA. Researchers will start with simpler organisms, such as microbes and plants, but hope to ultimately create strands of human genetic code. One of the group's organizers, Jef Boeke, director of the Institute for Systems Genetics at NYU School of Medicine, told CNBC that incorporating synthesized DNA into mammalian (or even human) cells could happen in four to five years. This project follows in the footsteps of the Human Genome Project (HGP), the 13-year, $2.7 billion project that enabled scientists to first decode the human genome. "HGP allowed us to read the genome, but we still don't completely understand it," said Nancy Kelley, the coordinator of the new effort, dubbed GP-write. High school biology covers the basic building blocks for DNA, called nucleotides — adenine (A), cytosine (C), guanine (G) and thymine (T). Humans' 3 billion pairs provide the blueprints for how to build our cells. The intention of GP-write is to provide a better fundamental understanding of how these pieces work together. Using synthesized genomes has both pragmatic and theoretical implications — it could lead to lower cost and higher quality of DNA synthesis, discoveries about DNA assembly in cells and the ability to test many DNA variations. "If you do that, you gain a much deeper understanding of how a complicated apparatus goes," Boeke said. Boeke likens the genome to a bicycle — you can only fully understand something once you take it apart and put it back together. "Really, a synthetic genome is an engine for learning new information." More from Modern Medicine: Medical breakthroughs are way behind for the hard of hearing In the land of Vikings, an ambitious effort to find a cancer cure New guidelines for prostate cancer screening Boeke is particularly excited about what he calls an "ultrasafe cell line." Certain types of mammalian cells intended to produce certain types of large molecule drugs, called biologics. "[Cell lines] have been cultured in dishes in labs for decades. But you can't engineer the genomes — the tools for doing that are quite crude, relatively speaking," Boeke said. Sometimes these cells get infected with a virus, and it completely shuts down drug production. A synthetic cell that lacked unnecessary genetic material could, evidence suggests, be virus-resistant, consistently producing useful drugs to treat disease. The results of GP-write could also lead to stem cell therapy that doesn't run the risk of infecting the patient with another disease, which appears to be what happened to one patient who received stem cell treatment in Mexico. Or they could create a line of microorganisms that could help humans generate some of their own amino acids — nutrients we usually get from food. These outcomes, of course, won't happen overnight. Boeke, who has spent years synthesizing yeast DNA, knows there will be plenty of technical hurdles. "Getting big pieces of DNA efficiently into mammalian cells, engineering them rapidly, these will be major challenges," he said. Scientists will also have to do that without breaking the bank. Right now, Kelley estimates that it costs 10 cents to synthesize every base pair, the bonded molecules that make up the double helix of DNA (start-up GenScript advertises even higher prices, at 23 cents for "economy"). Considering that humans have 3 billion base pairs. "If we can get that [cost] down to one cent per base pair, it would really make a difference," Kelley said. Since last May's meeting, Kelley, Boeke and their collaborators have published an article in Science about the project, as well as a white paper outlining its timeline. Close to 200 researchers and collaborators around the world have expressed interest in participating, Kelley says, ranging from institutional researchers to corporate scientists. Preliminary experiments are already underway, and the project organizers are discussing the project with companies as well as federal and state agencies that might help them reach their goal of raising $100 million this year. They estimate GP-write should cost less, in total, than the $3 billion Human Genome Project, though they have not provided more specific cost projections. It might not be so bad if these advances took some time. After news broke of the May meeting, some criticized the way the rollout was handled. "Given that human genome synthesis is a technology that can completely redefine the core of what now joins all of humanity together as a species, we argue that discussions of making such capacities real ... should not take place without open and advance consideration of whether it is morally right to proceed," read one op-ed, published in Cosmos. Boeke says a public and scientific discussion is exactly what the GP-write organizers intend to have. "I think articulation of our plan not to start right off synthesizing a full human genome tomorrow was helpful. We have a four- to five-year period where there can be plenty of time for debate about the wisdom of that, whether resources should be put in that direction or in another. Whenever it's human, everyone has an opinion and wants their voice to be heard. We want to hear what people have to say," Boeke said. Up to 250 people are expected at the New York Genome Center meeting, which will include discuss of applications, ethics and logistics behind the GP-write project. New technology that can help the 360 million people with hearing loss The race is on to stop a Zika virus epidemic in the US
News Article | November 29, 2016
Copenhagen, 2016-11-29 12:30 CET (GLOBE NEWSWIRE) -- The Carlsberg Forum series reflects the strong link between science and business. Each year, the Kaj Linderstrøm-Lang awards are given to prominent scientists for their achievements within biochemistry or physiology, the fields of science in which Kaj Linderstrøm-Lang, a professor at Carlsberg Research Laboratory in the period 1939-1959, distinguished himself as a pioneer. This year, Professor Henrik V. Scheller, Joint BioEnergy Institute, Lawrence Berkeley National Laboratory, USA and Professor Geoff Fincher, School of Agriculture, Food & Wine, The University of Adelaide, Australia received this year’s Kaj Linderstrøm-Lang Prize as an acknowledgement of their outstanding achievements on identifying and characterizing enzymes involved in synthesis and modification of the plant cell wall. The third Kaj Linderstrøm-Lang Prize was awarded to Professor Richard Henderson, MRC Laboratory of Molecular Biology, Cambridge, UK for his pioneering work towards obtaining high resolution atomic structures of membrane proteins and membrane protein complexes by electron cryomicroscopy. The prize is a plated gold medal and a financial personal award of DKK 40.000. Finally, the Emil Chr. Hansen Golden Medal was awarded to Jef Boeke, Director, Institute for Systems Genetics at New York University, for his seminal contributions to yeast genome scrambling and the design of synthetic yeast. The Emil Chr. Hansen Foundation sponsors the Emil Chr. Hansen Golden Medal. Professor Emil Chr. Hansen worked at the Carlsberg Laboratory from 1877-1909, and was the first to isolate a pure yeast that revolutionized the brewing industry. Birgitte Skadhauge, Head of Carlsberg Research Laboratory, says: “The distinguished work of Carlsberg Research Laboratory scientists Kaj Linderstrøm-Lang and Emil Chr. Hansen made it possible to have the high quality beers we have today. This year marks the 140th anniversary of the Carlsberg Research Laboratory, and we found it particularly important to celebrate the connection between beer and science this year by honouring not only Professors Richard Henderson, Geoff Fincher and Henrik Scheller but also Jef Boeke with the Emil Christian Hansen Golden Medal for their notable scientific contributions to business and society.” The program for this year’s Carlsberg Forum consisted of eight lectures by outstanding international scientists and businesspersons spanning trend-setting research in e.g. yeast, cereal-crops, food for health & well-being and new technologies. The business part of the program included lectures on business and health challenges in a globalized and rapidly changing world. In a special endnote address, Birgitte Skadhauge reviewed the Laboratory’s anniversary and the famed re-brew project. Scientists at the Laboratory made an extraordinary discovery in the old cellars of Carlsberg in Copenhagen, Denmark, some years ago. They discovered a very old Carlsberg bottle that surprisingly still contained living yeast cells. They grew and analyzed the cells, and, as it turns out, the bottle was one of the very first beers brewed with the original pure yeast from 1883 when Carlsberg democratized modern lager beers. Earlier this year, specially invited guests celebrated the Laboratory’s 140th anniversary by tasting, for the first time in more than a hundred years, the original Carlsberg quality lager, re-brewed by the Laboratory. Birgitte Skadhauge says: “What better way to take science to business than by re-brewing the father of quality lager. The Laboratory has pioneered beer quality since it was founded 140 years ago. On the eve of our anniversary, we are proud to have demonstrated scientifically why Carlsberg is probably the best beer in the world.” The movie premiere of Warner Bros’ documentary about the re-brew project premiered in Copenhagen and Fredericia, Denmark, on 24 and 25 November. A movie trailer is available on rebrewproject.com The Carlsberg Group is one of the leading brewery groups in the world, with a large portfolio of beer and other beverage brands. Our flagship brand – Carlsberg – is one of the best-known beer brands in the world and the Baltika, Carlsberg and Tuborg brands are among the eight biggest brands in Europe. More than 47,000 people work for the Carlsberg Group, and our products are sold in more than 150 markets. In 2015, the Carlsberg Group sold 120 million hectolitres of beer, which is more than 35 billion bottles of beer. Find out more at www.carlsberggroup.com.
PubMed | Institute for Systems Genetics and Hoffmann-La Roche
Type: | Journal: Journal of visualized experiments : JoVE | Year: 2015
The Synthetic Yeast Genome Project (Sc2.0) aims to build 16 designer yeast chromosomes and combine them into a single yeast cell. To date one synthetic chromosome, synIII(1), and one synthetic chromosome arm, synIXR(2), have been constructed and their in vivo function validated in the absence of the corresponding wild type chromosomes. An important design feature of Sc2.0 chromosomes is the introduction of PCRTags, which are short, re-coded sequences within open reading frames (ORFs) that enable differentiation of synthetic chromosomes from their wild type counterparts. PCRTag primers anneal selectively to either synthetic or wild type chromosomes and the presence/absence of each type of DNA can be tested using a simple PCR assay. The standard readout of the PCRTag assay is to assess presence/absence of amplicons by agarose gel electrophoresis. However, with an average PCRTag amplicon density of one per 1.5 kb and a genome size of ~12 Mb, the completed Sc2.0 genome will encode roughly 8,000 PCRTags. To improve throughput, we have developed a real time PCR-based detection assay for PCRTag genotyping that we call qPCRTag analysis. The workflow specifies 500 nl reactions in a 1,536 multiwell plate, allowing us to test up to 768 PCRTags with both synthetic and wild type primer pairs in a single experiment.
Mitchell L.A.,Institute for Systems Genetics |
Phillips N.A.,Institute for Systems Genetics |
Lafont A.,Hoffmann-La Roche |
Martin J.A.,Institute for Systems Genetics |
And 2 more authors.
Journal of Visualized Experiments | Year: 2015
The Synthetic Yeast Genome Project (Sc2.0) aims to build 16 designer yeast chromosomes and combine them into a single yeast cell. To date one synthetic chromosome, synIII1, and one synthetic chromosome arm, synIXR2, have been constructed and their in vivo function validated in the absence of the corresponding wild type chromosomes. An important design feature of Sc2.0 chromosomes is the introduction of PCRTags, which are short, re-coded sequences within open reading frames (ORFs) that enable differentiation of synthetic chromosomes from their wild type counterparts. PCRTag primers anneal selectively to either synthetic or wild type chromosomes and the presence/absence of each type of DNA can be tested using a simple PCR assay. The standard readout of the PCRTag assay is to assess presence/absence of amplicons by agarose gel electrophoresis. However, with an average PCRTag amplicon density of one per 1.5 kb and a genome size of ~12 Mb, the completed Sc2.0 genome will encode roughly 8,000 PCRTags. To improve throughput, we have developed a real time PCR-based detection assay for PCRTag genotyping that we call qPCRTag analysis. The workflow specifies 500 nl reactions in a 1,536 multiwell plate, allowing us to test up to 768 PCRTags with both synthetic and wild type primer pairs in a single experiment. © 2015 Journal of Visualized Experiments.