A spotlight on global collaboration in the Sc2.0 yeast consortium

Abstract

The Synthetic Yeast Genome Project (Sc2.0) is an international collaboration that aims to create and optimize synthetic versions of each Saccharomyces cerevisiae chromosome, with the ultimate goal of assembling a yeast organism with a synthetic with design features facilitating applications in synthetic biology and engineering projects. The consortium research groups are global, and, here, we highlight the work of the China-based Sc2.0 researchers and their thoughts on the future of Sc2.0 and synthetic biology.

The synthetic yeast genome project (Sc2.0) is an international collaboration which aims to create and optimize synthetic versions of each Saccharomyces cerevisiae chromosome, with the ultimate goal of assembling a yeast organism with a synthetic with design features facilitating applications in synthetic biology and engineering projects. The consortium research groups are global, and here we highlight the work of the China based Sc2.0 researchers and their thoughts on the future of Sc2.0 and synthetic biology.

Main text

Future of synthetic biology

Professor Junbiao Dai

Agricultural Genomes Institute at Shenzhen, Chinese Academy of Agricultural Sciences

In the near future, I think the most exciting development in synthetic biology will be the complete synthesis of designer chromosomes in different organisms, starting from the budding yeast, as published in this collection. More importantly, the combination of all 16 synthetic chromosomes into a single yeast cell, generating a strain containing an entire synthetic genome, will not only be a milestone in synthetic genomics but also open the door for dissecting many interesting biological questions in eukaryotes, such as genome plasticity (how genomes change over time), which is important in evolution and disease biology. Furthermore, it is exciting to see that the design and synthesis of genomes of multicellular organisms is under way, which could potentially offer a better chassis for advancing our understanding of complex biological systems.

International collaborations are absolutely key for our group's work. In Sc2.0, we worked together as a big family toward the project goal. We were able to share protocols, provide training when necessary, discuss and solve various “bugs” in experiments (cases where the synthetic chromosome is not performing the same as the wild type), think of different biological questions for each chromosome, and coordinate submission and publication of the manuscripts. I am very happy to be able to work with all members in the consortium. Based on this collaboration, we initiated GP-write China to expand our research scope to the Sc3.0 project, which aims to simplify and reconstitute the yeast genome, and the synMoss project, which plans to generate a synthetic moss.

The wide impact of sc2.0

Professor Huanming Yang

University of Chinese Academy of Sciences (UCAS), Peking Union Medical College (PUMC), and BGI Research

I think Sc2.0 is a milestone in genomics and synthetic biology. It is the first monocellular karyotic genome redesigned and wholly synthesized by humans, with the genome size approximately 10 times of Synthia (the minimal synthetic bacterial cell) by Dr. Craig Venter’s team. It lays the foundation for our plans for other multicellular organisms with genomes up to 10 times the size, e.g., C. elegans, Drosophila, or Arabidopsis, which are currently at the redesign stage.

The organization of our collaboration was based on the Human Genome Project (HGP) and “sister projects” e.g., HapMap, the 1000 Genomes Project (G1K), the International Project on Cancer Genomes (IPCG), and the Earth Biogenome Project (EBP), from which I learned a lot from other coordinators. We first “raise the banner of global collaboration even higher,” as I said when chairing the first meeting of Sc2.0. Until now, it remains the largest collaborative project in synthetic biology. I do have to thank all consortium members for their “spirit of collaboration” as I proposed the HGP spirit: “Owned by All (the opportunity), Done by All (through vast global collaboration) and Shared by All (results are freely available).” The genome was redesigned by labs in the UK and China, which included the idea to have all tRNA genes as a single chromosome, and the synthesis tasks were divided based on chromosomes using the strategy invented by the USA team—genomic segment replacement based on natural mechanisms of homologous recombination. I was so excited that all the labs completed the jobs with high quality ahead of schedule. It is another brilliant example of international collaboration that will be followed for other projects.

This is what I always say: collaborations come from mutual trust and result in all-life friendships (in addition to the scientific results).

Communication is key

Professor Isak S. Pretorius

Macquarie University

Great discoveries and technological improvements invariably involve the cooperation of many bright minds. Breakthroughs in our understanding of scientific fundamentals and innovations are rarely the result of one person’s endeavor. When Sc2.0 was conceived, an approach termed “committed collaboration” was adopted. This requires an exchange of ideas in a spirit of mutual trust. A common theme in the partnership has always been mutual trust coupled with competence and effective communication. Whether the researchers worked independently or as a group, effective communication networks were required to inspire and inform all parties. This partnership has grown tighter over the past 10 years. It also means that we look out for each other and help one another so that we can achieve our shared goals. Within the Sc2.0 consortium, we are learning to collaborate, and we are collaborating to learn. We are committed to the principle of co-creation and co-training of “next-generation” researchers and the future workforce. Over geopolitical and disciplinary boundaries, we are exploring new ways to work with each other to find new ways forward in our resolve to replace S. cerevisiae’s 16 native chromosomes with 16 chemically synthesized chromosomes. We are in this together. We are committed to delivering the world’s first synthetic eukaryotic genome in the foreseeable future. Without this deep global partnership built on shared goals, mutual trust, expertise, competence, and total commitment to co-creation, it would be impossible to deliver on an ambitious and complex project of this nature and scale. This truly global partnership is the key to our success.

Global research links

Professor Patrick Cai

The University of Manchester

The Sc2.0 project started as an undergraduate course, “Build a Genome,” in Johns Hopkins when I was a postdoc in Jef Boeke’s lab back in 2010. It was a great course to teach undergraduates how to make synthetic DNA, but it will take a long time to complete one chromosome let alone the genome. Then I initiated the international consortium with Jef and gradually rolled it out as an international community effort and probably the largest synthetic biology project in the public domain. We worked with teams from China, Australia, Singapore, the UK, and the US to complete this very ambitious project, which seemed to be a mission impossible when it first started.

It is not so much about the distance but more about the understanding of different research cultures that makes it challenging to coordinate a large consortium like this. Luckily, I grew up in China and was educated in the UK and US, and this international background allows me to effectively communicate with my Chinese collaborators and other international collaborators. The consortium has annual meetings and frequent Zoom calls, which have been really great to facilitate the communications.

Synthetic biology in China

Professor Chantal Yue Shen

Institute of Biochemistry, BGI Research, China National GeneBank

The Sc2.0 yeast genome project serves as a significant milestone project in the field of synthetic genomics, following the completion of Synthia. Together with teams from Tianjin University and Tsinghua University, we were honored to become an early member of the Sc2.0 international consortium in 2010 and represent China to take the task of engineering a total of six chromosomes. Moving from genome decoding (sequencing) to genome recoding (synthetic genomics) is an inevitable trend for the development of life science. Thus, the implementation of Sc2.0 has promoted the establishment of China’s foundation in terms of talent and technology, especially in areas including DNA synthesis and large DNA construction and genome design. It will pave the way for potential industrial applications such as the ongoing efforts of recoding Corynebacterium glutamicum genome (a gram-positive bacteria used to synthesize amino acids) and the exploration of larger and more complex multicellular systems such as initiatives announced by GP-write China.

The biggest challenge for the consortium is effectively coordinating and managing the project goal and milestones to be achieved by different groups within a defined timeline. Since each group has different technical backgrounds and foundations, the tasks and problems encountered vary for different groups. In addition, such significant workloads require a long-term investment (over a decade for the Sc2.0 consortium). It is essential to set goals and milestones reasonably. Therefore, consensus needs to be formed in several aspects, which might involve defining clear goals, developing a robust project management plan, building relationships with all consortium members to foster trust and effective collaboration and communication, and committing to sharing technology and resources for troubleshooting or greater efficiency.

Benefits of a global team

Professor Matthew Chang

National University of Singapore

Our engagement with international Sc2.0 collaborators has been an invaluable journey for my research team. From the outset, it has provided us with access to a diverse array of talent and expertise from around the globe. Working alongside these esteemed partners, we've tapped into a wealth of knowledge and innovative ideas, significantly enhancing the caliber of our research. Furthermore, our partnership with Sc2.0 collaborators has facilitated access to state-of-the-art technologies and resources that align exceptionally well with the NUS (National University of Singapore) BioFoundry. This collaboration has empowered us to expedite our research projects and attain milestones with greater efficiency.

The global perspective brought by our Sc2.0 collaborators has broadened our horizons, prompting us to think beyond the immediate confines of our research environment. This intercultural exchange of ideas has cultivated creativity and a deep understanding of the scientific challenges we encounter. Through our ties with Sc2.0 partners, we've expanded our professional networks and bolstered our standing in the scientific community. Such exposure has proven instrumental in drawing top-tier talent to our research group and in garnering external funding for our projects.

In conclusion, our partnership with Sc2.0 collaborators not only has amplified the quality and scope of our research but has also solidified our group's reputation as a leader in our field. We eagerly anticipate continued collaboration and the possibility of achieving even more monumental scientific milestones in the future.

Yeast biotechnology

Professor Yingjin Yuan

Tianjin University

Engineered yeast is an important production platform for the biosynthesis of high-value chemical compounds. Through the Sc2.0 project, unprecedented chassis cells can be developed, enhancing biosynthetic capabilities (Zhou et al. 2023). The SCRaMbLE system of Sc2.0 has proven effective in generating new chassis cells with a high yield of carotenoids (Jia et al., 2018) or various environmental tolerances (Zhou et al. 2021). Furthermore, the strides made in DNA assembly technologies by Sc2.0 enable integration of foreign genes on a larger scale, in a more efficient and rapid manner.

The inception and evolution of Sc2.0 has been driven by our shared recognition of the immense significance of a synthetic yeast genome. This endeavor has propelled the advancement of our individual research projects and made substantial strides in synthetic genomics and biology. My lab focuses on biochemical engineering, with an emphasis on leveraging modular synthetic components to manipulate yeast metabolism. Coincidentally, while participating in the international Genetically Engineered Machine (iGEM) competition, I became acquainted with the Synthetic Yeast Genome Project led by Jef Boeke. The audacious and innovative concept underlying this initiative greatly enthused me. We collectively elevated Sc2.0 into an international venture. The headway achieved by Sc2.0 has hastened our research. The team from Tianjin University, for example, successfully synthesized chromosomes V and X while also pioneering bug mapping and a precise repair method (Xie et al., 2017 and Wu et al., 2017). Additionally, the Sc2.0 project has fostered the growth of a cohort of young scientists endowed with international partnership, thus enabling them to explore the frontiers of synthetic biology.