New York Genome Center (NYGC) hosts 4th International Sc2.0 and synthetic Genomes meeting

sc2-meeting-2015The fourth international meeting of our group was held at the NYGC in lower Manhattan on July 16-17, 2015, and organized by Jef Boeke, Nancy J. Kelley and Leslie Mitchell. At the last meeting, our group decided to expand to a two day meeting and also to expand the topic area to include discussion and presentations on other synthetic genomes. Jef Boeke kicked off the meeting with an overview of the Sc2 project, and there were two nuts and bolts workshops where each team explained progress and challenges. Highlights included panel discussions on synthetic genomes and society and discussions of what is the next multicellular genome that should be synthesized. Sessions highlighting the relationship of yeast genomes to the flavors and behaviors of certain alcoholic beverages were discussed by Daniel Johnson and Sakkie Pretorius of the Australian Wine Research Institute and by Troels Prahl of White Labs with his colleague Toby Richardson of Synthetic Genomics Inc. Representatives of DNA synthesis and robotics and instrument companies were also in attendance. A very exciting meeting all around! We hope to see you in Edinburgh next year:

5th International Sc2.0 and Synthetic Genomes meeting, Dynamic Earth, Edinburgh, July 8-9, 2016, Main Organizer: Patrick Cai. Keynote speakers are Jasper Rine and Jim Collins.

Build-a-Genome Network Workshop, Aug 14-16 Loyola University Maryland, Baltimore MD

The Build-a-Genome (BAG) course offers undergraduate students an exceptional opportunity to participate in the cutting-edge research of the Synthetic Yeast Project. BAG offers students an authentic laboratory experience where they perform fundamental techniques in synthetic genomics, present and critique their data, and troubleshoot experiments until successful. By completion of the course, students who worked on synthetic chromosome III became so fluent in molecular and synthetic biology techniques that they produced numerous synthetic chromosome “building blocks” and earned authorship on that milestone research paper. After being established at Johns Hopkins University, BAG franchises were established at Loyola University Maryland and Tianjin University in China. Thanks to funding from the National Science Foundation RCN-UBE program, the Build-a-Genome Network has now been established with the goal of broadening the number of colleges and universities that offer the BAG course.

A national workshop for the Build-a-Genome Network will be held from August 14th to 16th at Loyola University Maryland in Baltimore. This meeting will:

(1) Introduce new members to the Synthetic Yeast Project and the BAG workflow through a series of talks, hands-on bioinformatics exercises, and wet-lab activities.
(2) Discuss strategies for adapting the BAG course to diverse undergraduate institutions. We seek to preserve the most attractive features of the BAG course while confronting the logistical hurdles that may arise when implementing research-intensive courses at undergraduate institutions.
(3) Develop course learning objectives and assessment tools for different variations of the BAG course.

These activities will create a network of expertise and “ready-to-implement” frameworks, both of which will allow network participants to implement the BAG curriculum (or similar synthetic genomics projects) at a broad range of academic institutions. For more information please contact Rob Newman (, Eric Cooper (, or Lisa Scheifele (

First SAVI-sponsored joint US-China paper on Sc2.0 published

Two graduate students from Tianjin University, Qiuhui Lin and Jia Bin, from the laboratory of Yingjin Yuan at Tianjin University traveled to Johns Hopkins University where they worked in the lab of Jef Boeke for several months, in an effort to exchange scientific information, and develop new methods.  Working with postdoctoral fellow Leslie Mitchell and graduate students Jingchuan Luo and Zhuwei Xu they developed efficient and standardized methods for assembling “Minichunks” of 2.5-4 kb, stringing together Building Blocks previously made by JHU “Build A Genome” students. Then the “RADOM” method, which produces up to 10 kb fragments “in yeasto”, used the Build A Genome Class, led by Karen Zeller, as a testbed, and the workflow was implemented in BioStudioDb by Kun Yang.  The work is published in ACS SynBio and sponsored by the NSF SAVI program..
The RADOM method

The RADOM method

3d International Synthetic Yeast Genome (Sc2.0) Consortium Meeting, Taormina, Italy on June 20, 2014 – sponsored by NSF SAVI

We are pleased to announce that this summer on June 20th, we will be hosting the 3d International Synthetic Yeast Genome (Sc2.0) Consortium Meeting at the Hotel Villa Diodoro, Sicily, Italy. This day-long meeting is now open for registration.  Notably it will be held the day after the International Synthetic and Systems Biology Summer School, so it will be easy to attend both activities.

The Synthetic Yeast Genome Project (Sc2.0) is synthesizing and constructing a modified version of the Saccharomyces cerevisiae genome to test biological questions and give new functions.

We will be bringing those around the world involved in the Sc2.0 project together to discuss progress on the synthetic genome, opportunities to use the strains and tools of the project, and related projects in synbio and sysbio. This meeting is open to all interested in Sc2.0 and we encourage you (and your colleagues) to register if you’d like to attend.

Please note the happy smiling faces of the participants at the 2d Sc2.0 meeting in London — this time we will sample some Sicilian beers and maybe even wines!


NYU Langone Medical Center Press Release

Scientists Synthesize First Functional “Designer” Chromosome in Yeast

Study reports major advance in synthetic biology

March 27, 2014 (All day)

An international team of scientists led by Jef Boeke, PhD, director of NYU Langone Medical Center’s Institute for Systems Genetics, has synthesized the first functional chromosome in yeast, an important step in the emerging field of synthetic biology, designing microorganisms to produce novel medicines, raw materials for food, and biofuels.

Over the last five years, scientists have built bacterial chromosomes and viral DNA, but this is the first report of an entire eukaryotic chromosome, the threadlike structure that carries genes in the nucleus of all plant and animal cells, built from scratch. Researchers say their team’s global effort also marks one of the most significant advances in yeast genetics since 1996, when scientists initially mapped out yeast’s entire DNA code, or genetic blueprint.

“Our research moves the needle in synthetic biology from theory to reality,” says Dr. Boeke, a pioneer in synthetic biology who recently joined NYU Langone from Johns Hopkins University.

“This work represents the biggest step yet in an international effort to construct the full genome of synthetic yeast,” says Dr. Boeke. “It is the most extensively altered chromosome ever built. But the milestone that really counts is integrating it into a living yeast cell. We have shown that yeast cells carrying this synthetic chromosome are remarkably normal. They behave almost identically to wild yeast cells, only they now possess new capabilities and can do things that wild yeast cannot.”

In this week’s issue of Science online March 27, the team reports how, using computer-aided design, they built a fully functioning chromosome, which they call synIII, and successfully incorporated it into brewer’s yeast, known scientifically as Saccharomyces cerevisiae.

The seven-year effort to construct synIII tied together some 273, 871 base pairs of DNA, shorter than its native yeast counterpart, which has 316,667 base pairs. Dr. Boeke and his team made more than 500 alterations to its genetic base, removing repeating sections of some 47,841 DNA base pairs, deemed unnecessary to chromosome reproduction and growth. Also removed was what is popularly termed junk DNA, including base pairs known not to encode for any particular proteins, and “jumping gene” segments known to randomly move around and introduce mutations. Other sets of base pairs were added or altered to enable researchers to tag DNA as synthetic or native, and to delete or move genes on synIII.

“When you change the genome you”re gambling. One wrong change can kill the cell,” says Dr. Boeke. “We have made over 50,000 changes to the DNA code in the chromosome and our yeast still live. That is remarkable. It shows that our synthetic chromosome is hardy, and it endows the yeast with new properties.”

The Herculean effort was aided by some 60 undergraduate students enrolled in the “Build a Genome” project, founded by Dr. Boeke at Johns Hopkins. The students pieced together short snippets of the synthetic DNA into stretches of 750 to 1,000 base pairs or more. These pieces were then assembled into larger ones, which were swapped for native yeast DNA, an effort led by Srinivasan Chandrasegaran, PhD, a professor at Johns Hopkins. Chandrasegaran is also the senior investigator of the team’s studies on synIII.

Student participation kicked off what has become an international effort, called Sc2.0 for short, in which several academic researchers have partnered to reconstruct the entire yeast genome, including collaborators at universities in China, Australia, Singapore, the United Kingdom, and elsewhere in the U.S.

Yeast chromosome III was selected for synthesis because it is among the smallest of the 16 yeast chromosomes and controls how yeast cells mate and undergo genetic change. DNA comprises four letter-designated base macromolecules strung together in matching sets, or base pairs, in a pattern of repeating letters. “A” stands for adenine, paired with “T” for thymine; and “C” represents cysteine, paired with “G” for guanine. When stacked, these base pairs form a helical structure of DNA resembling a twisted ladder.

Yeast shares roughly a third of its 6,000 genes—functional units of chromosomal DNA for encoding proteins — with humans. The team was able to manipulate large sections of yeast DNA without compromising chromosomal viability and function using a so-called scrambling technique that allowed the scientists to shuffle genes like a deck of cards, where each gene is a card. “We can pull together any group of cards, shuffle the order and make millions and millions of different decks, all in one small tube of yeast,” Dr. Boeke says. “Now that we can shuffle the genomic deck, it will allow us to ask, can we make a deck of cards with a better hand for making yeast survive under any of a multitude of conditions, such as tolerating higher alcohol levels.”

Using the scrambling technique, researchers say they will be able to more quickly develop synthetic strains of yeast that could be used in the manufacture of rare medicines, such as artemisinin for malaria, or in the production of certain vaccines, including the vaccine for hepatitis B, which is derived from yeast. Synthetic yeast, they say, could also be used to bolster development of more efficient biofuels, such as alcohol, butanol, and biodiesel.

The study will also likely spur laboratory investigations into specific gene function and interactions between genes, adds Dr. Boeke, in an effort to understand how whole networks of genes specify individual biological behaviors.

Their initial success rebuilding a functioning chromosome will likely lead to the construction of other yeast chromosomes (yeast has a total of 16 chromosomes, compared to humans’ 23 pairs), and move genetic research one step closer to constructing the organism’s entire functioning genome, says Dr. Boeke.

Dr. Boeke says the international team’s next steps involve synthesizing larger yeast chromosomes, faster and cheaper. His team, with further support from Build a Genome students, is already working on assembling base pairs in chunks of more than 10,000 base pairs. They also plan studies of synIII where they scramble the chromosome, removing, duplicating, or changing gene order.

Detailing the Landmark Research Process

Before testing the scrambling technique, researchers first assessed synIII’s reproductive fitness,  comparing its growth and viability in its unscrambled from  — from a single cell to a colony of many cells — with that of native yeast III. Yeast proliferation was gauged under 19 different environmental conditions, including changes in temperature, acidity, and hydrogen peroxide, a DNA-damaging chemical. Growth rates remained the same for all but one condition.

Further tests of unscrambled synIII, involving some 30 different colonies after 125 cell divisions, showed that its genetic structure remained intact as it reproduced. According to Dr. Boeke, individual chromosome loss of one in a million cell divisions is normal as cells divide. Chromosome loss rates for synIII were only marginally higher than for native yeast III.

To test the scrambling technique, researchers successfully converted a non-mating cell with synIII to a cell that could mate by eliminating the gene that prevented it from mating.

Funding support for these experiments was provided by National Science Foundation, the National Institutes of Health, and Microsoft. Corresponding federal grant numbers are MCB-0718846 and GM-077291. Additional funding support was provided by fellowships from La Fondation pour la Recherche Médicale, Pasteur-Roux, National Sciences and Engineering Research Council of Canada, U.S. Department of Energy, and grants from the Exploratory Research Grant from the Maryland Stem Cell Research Fund and the Johns Hopkins University Applied Physics Laboratory.

Besides the teams at NYU Langone and Johns Hopkins, other scientific teams involved in the global Sc2.0 research effort are based at Loyola University in Baltimore, Md; BGI in Shenzhen, China; Tianjin University in China; Tsinghua University in China; MacQuarie University in Sydney, Australia; the Australian Wine Institute in Adelaide, Australia; the National University of Singapore; Imperial College, London, England; and the University of Edinburgh in Scotland.

£1 Million from BBSRC and EPSRC for Synthetic Yeast

David Willetts, Minister for Universities and Science, announced nearly £1M funding for synthetic yeast at the Sixth International Meeting on Synthetic Biology (SB6.0) at Imperial College London on Thursday (July 11). David Willetts said: Sc2.0 project “is truly groundbreaking and pushes the boundaries of synthetic biology. Thanks to this investment, UK scientists will be at the centre of an international effort using yeast – which gives us everything from beer to biofuels – to provide new research techniques and unparalleled insights into genetics. This will impact important industrial sectors like life sciences and agriculture.” Funding for the yeast project is part of a £60M package for synthetic biology.

Dr.Tom Ellis, Lecturer in Synthetic Biology at Imperial College London, said: “We are excited to be welcoming our new international consortium partners to London to discuss Sc2.0. Having recently secured funding for the UK to be part of this ground-breaking project, we are looking forward to getting started and being part of the action. It”s a perfect fit for our work in synthetic biology here at Imperial, where we really view yeast as a tiny factory that can be tooled-up to produce new molecules. A synthetic genome will allow us to reprogram yeast and our goal is to use it to produce new antibiotics as resistance arises to existing ones.”

When completed, synthetic yeast will be the first time scientists have built the whole genome of a eukaryotic organism – those organisms, like animals and plants, which store DNA within a nucleus. Scientists can then design different strains of synthetic yeast that contain genes to make commercially valuable products such as chemicals, vaccines or biofuels.

Professor Boeke, the overall head of the project at Johns Hopkins Medical School in Baltimore, said: “Sc2.0, once completed, will provide unparalleled opportunities for asking profound questions about biology in new and interesting ways, such as: How much genome scrambling generates a new species? How many genes can we delete from the genome and still have a healthy yeast? And how can an organism adapt its gene networks to cope with the loss of an important gene? Moreover, genome scrambling may find many uses in biotechnology, for example in the development of yeast that can tolerate higher ethanol levels.”

Alongside BBSRC and EPSRC, major funders for the Sc2.0 consortium members in their respective countries include the US National Science Foundation (NSF), the US Department of Energy, China”s Ministry of Science and Technology (MoST) and the Tsinghua University Initiative Scientific Research Program.

More related news:

2nd International Synthetic Yeast Genome (Sc2.0) Consortium Meeting, London, UK, July 12, 2013

We are pleased to announce that this summer on Friday 12th July, we will be hosting the 2nd International Synthetic Yeast Genome (Sc2.0) Consortium Meeting here in the UK at Imperial College London. This day-long meeting is now open for registration.  Notably it will be held the day after the SB6.0 meeting, so it will be easy to attend both.

The Synthetic Yeast Genome Project (Sc2.0) is synthesizing and constructing a modified version of the S. Cerevisiae genome to test biological questions and give new functions.

We will be bringing those around the world involved in the Sc2.0 project together to discuss progress on the synthetic S. cerevisiae genome and opportunities to use the strains and tools of the project. This meeting is open to all interested in Sc2.0 and we encourage you (and your colleagues) to register if you”d like to attend.

Rumor has it microbrew beer samples will be available – as it should be for a yeast meeting. See you in London?

Collaboration with Dalton School – high school science students

Over 150 students have participated in the Build-A-Genome course at Johns Hopkins University since its inception 5 years ago. This hands-on experience with the Sc2.0 project allows participants, including high school students, undergraduates, and faculty members, to gain extensive experience in the fields of synthetic and molecular biology and demonstrates the unique didactic potential of Sc2.0. This year we extended our effort in this arena and engaged in a formal collaboration with the Dalton School, a private high school in Manhattan. Working with Dr. Jennifer Hackett, a former PhD student at Johns Hopkins University and now teacher at Dalton, 9 talented grade ten biology students built 80 Cre-EBD constructs that will be used to activate SCRaMbLE, the inducible evolution system encoded by the Sc2.0 genome. The students assembled these constructs using ‘yeast Golden Gate’ (yGG), our standardized assembly method that enables fast and efficient construction of S. cerevisiae transcription units. Importantly, the students transformed these constructs into a yeast strain encoding a synthetic chromosome and subsequently induced SCRaMbLE; these students are now some of the only people in the world who have inducibly evolved a synthetic yeast chromosome.

Dr. Jenny Hackett (right) and eight of her students. Pictured behind are data from a SCRaMbLE induction experiment.

The First International Coordination Meeting on the Synthetic Yeast Project to Propel Synthetic Biology Forward

The first international meeting on Synthetic Yeast Genome, Sc2.0 project participants:

Funders: NSF (USA); MoST (China); NSFC (China); BBSRC (UK); Council of Scientific and Industrial Research (India); Hong Kong Research Grants Council

Academia: Johns Hopkins University (USA); BGI, Tianjin University, Tsinghua University (China); Imperial College London, The University of Edinburgh (UK); Institute of Genomics and Integrative Biology, Pondicherry University (India); Hong Kong University, Hong Kong University of Science and Technology, Chinese University of Hong Kong (Hong Kong); Institut Pasteur (France); Catholic U Louvain la Neuve (Belgium)

April 17, 2012, China  – The international coordination meeting on the synthetic yeast project (Sc2.0 PROJECT), co-organized by Johns Hopkins University (JHU), BGI and Tsinghua University with the support of National Science Foundation (NSF), was held at the Wenjin Hotel, Beijing, China. This was the first international research coordination meeting on the synthetic yeast project aiming to develop new technological strategies and effective approaches to promote further research on this project as well as to boost the development of synthetic biology.

The meeting was attended by over 40 officials and experts from governments, outstanding scientific research institutes and colleges, including Ministry of Science and Technology, China, The National Science Foundation of China, The National Science Foundation (NSF), U.S.A., Biotechnology and Biological Sciences Research Council (BBSRC), United Kingdom, Council of Scientific and Industrial Research, India, Tianjin University, China, Hong Kong University, China, among others. At this meeting, Johns Hopkins University and The Centre for Synthetic Biology and Innovation (CSynBI) at Imperial College London signed a collaborative research agreement for their role in the Sc2.0 PROJECT. Imperial College will initiate the complete synthesis of yeast chromosome 11, bringing genome-scale synthetic biology to the UK for the first time.

Synthetic biology is a new emerging discipline, which is motivated by advances in molecular cell sciences, systems biology and the advent of two foundational technologies, DNA sequencing and DNA synthesis. The purpose of synthetic biology is to design synthetic biological systems by utilizing systematically engineered micro-organisms for the production of biofuels and drugs, providing a unique opportunity for researchers to study many profound life science questions and generate vital industrial applications.

The Sc2.0 PROJECT, initiated by Johns Hopkins University School of Medicine, is the first synthetic eukaryotic cell genome project. As one of the principal investigators of the project, Dr. Jef Boeke, Director of the High Throughput Biology Center, Johns Hopkins University School of Medicine, delivered a detailed presentation on the overview of the project and its profound impact in the field of synthetic biology. He said, “This meeting provides an opportunity for further boosting the research and applications of the Sc2.0 PROJECT. With the achievements of this project, I believe that we can seek much better solutions to face the challenges of the future, such as world energy shortage.”

After that, experts in different organizations, combining experimental studies with the prospective for synthetic biology, gave excellent presentations and participated in active discussions. Professor Guanhua Xu, Chairman of Advisory Group on The Fifth Major Project of Chinese National Programs for Fundamental Research and Development (973 Program), stated, “The accomplishment of Sc2.0 project will serve as a landmark for important milestones in the development of synthetic biology.”

Professor Huanming Yang, Chairman of BGI, said, “The rapid development of high-throughput sequencing technologies have led to a revolution in OMIC-related areas, which also greatly facilitates the studies on synthetic biology. With solidarity and international cooperation, I believe we will be able to explore more opportunities for valuable research in human disease and biomedical areas.”