Biology team makes breakthrough in synthetic yeast project – Phys.Org

March 9, 2017 Sacharomyces cerevisiae cells in DIC microscopy. Credit: Wikipedia.

Led by Tianjin University Professor Ying-Jin Yuan, TJU's synthetic biology team has completed the synthesis of redesigned yeast chromosomes synV and synX with the two studies published in Science on March 10, 2017.

The publications are part of the effort to chemically synthesize the designer yeast genome (Sc 2.0), in collaboration with NYU and John Hopkins in the US, Tsinghua University, BGI-Shenzhen in China, the University of Edinburgh in the UK, and the Institut Pasteur and Sorbonne Universits in France, as well as industry partners.

TJU is keen to integrate frontier science into student training. During the synthesis of the designer chromosome SynV, the "Build-A-Genome (BAG) China" course played a crucial role. In this innovative educational course, sixty-one students participated in the construction of building blocks and minichunks for synthetic chromosome V, although the majority of the students had little or no experience in DNA synthesis before. Through the BAG training, they advanced experimental skills, and obtained first-hand experiences essential to promote their trouble-shooting ability. Several students became specialists in DNA synthesis and constructed DNA segments with significant complicated sequences. A selection of them went on to continue their education in the synthetic biology field by undertaking Ph.D programs in China, the US, Europe and other countries.

"The goal of the BAG course at TJU is to train the next generation of synthetic biologists with a global perspective, innovative spirit, and practical abilities", said Professor Yuan. This goal was reached during the process of the Sc2.0 project, linking the course to practical scientific work. The first authors of the synV and synX articles, Ph.D candidates from Yuan's team, Zexiong Xie and Yi Wu, were participants of the BAG course. As a combination of the international science community and the educational system, BAG provided an elegant model to inspire the next generation scientists towards future research on synthetic biology.

Pursuing construction of the synthetic eukaryotic chromosome perfectly matching the designer sequence, the research team overcame significant obstacles. With all the 3331 bp randomly distributed mutations and other unpredictable events corrected in the designed sequence and performing with a similar fitness compared with native strains, the completed synV chromosome supported the underlying design principles of Sc2.0. After the paper was originally submitted, the team continued their corrections, leading to the title of the synV article being changed from "approaching a variant-free designer chromosome" to "'perfect' designer chromosome V". "Together with my colleagues, I spent almost 18 months mapping the bugs and correcting errors that led to the yeast being non-viable or having growth defects," says Xie, described the study of yeast chromosome synV.

Aiming to provide a model with which to study human ring chromosome disorders, the linear synV was converted to a ring synthetic chromosome, and it can extend genome design principles, as well as providing an insight into genomic rearrangement and ring chromosome evolution.

Certain genetic alternations in the chromosome would affect cell fitness and cause "bugs"; debugging is therefore imperative for successfully building a synthetic genome. The malfunction of synthetic genomes remains one of the most common obstacles, as it is difficult to uncover the underlying reasons. In a bid to tackle this problem, TJU developed a highly efficient debugging method called pooled PCRTag mapping (PoPM) by using a pooling strategy and the Sc2.0 PCRTag system, which is generalized to watermarked synthetic chromosomes. PoPM is a powerful tool for synthetic yeast genome debugging which accelerated the progress of the whole Sc2.0 project. "During synX assembly, the PoPM method was applied to identify and eliminate genetic alternations that affect cell fitness, sequences we refer to as "bugs", and several details of yeast biology were uncovered by debugging. PoPM represents an efficient strategy for phenotype-genotype mapping which will be applicable for expanding understanding of yeast genomic and cellular functions" according to Wu.

Explore further: Making 'designer genes' from scratch begins with yeast

More information: "Bug mapping and fitness testing of chemically synthesized chromosome X," Science (2017). DOI: 10.1126/science.aaf4706 "'Perfect' designer chromosome V and behavior of a ring derivative," Science (2017). DOI: 10.1126/science.aaf4704

Journal reference: Science

Provided by: Tianjin University

Australia is to play a significant role in the quest for artificial life as it joins an international project to create the world's first synthetic yeast, we can announce today.

NYU Langone yeast geneticists report they have developed a novel tooldubbed "the telomerator"that could redefine the limits of synthetic biology and advance how successfully living things can be engineered or constructed ...

In the quest to understand genomes -- how they're built, how they're organized and what makes them work -- a team of Johns Hopkins researchers has engineered from scratch a computer-designed yeast chromosome and incorporated ...

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 ...

(Phys.org) A multinational effort to replicate the genome of brewer's yeast has been launched. Led by Professor Jef Boeke of John Hopkins University in Baltimore, and with teams in China, India, Great Britain and other ...

Researchers at the J. Craig Venter Institute (JCVI), a not-for-profit genomic research organization, published results today describing new methods in which the entire bacterial genome from Mycoplasma mycoides was cloned ...

Researchers at the University of Arizona have found a promising way to prevent the loss of millions of tons of crops to a fungus each year, offering the potential to dramatically improve food security, especially in developing ...

Finnish and Estonian researchers have discovered and identified 16 new fungus gnat species in the Amazonia. The diverse gnat species maintain exceptionally rich parasitoid wasp species, which shows the importance of interdependence ...

A team of researchers with members from several institutions in India has found evidence of ostrich relatives living in India as far back as 25,000 years ago. In their paper uploaded to the open access site PLOS ONE, the ...

A new mathematical model could help clarify what drove the evolution of large brains in humans and other animals, according to a study published in PLOS Computational Biology.

Geneticists from the Universities of Manchester and Bath are celebrating the discovery of the elusive 'greenbeard gene' that helps explain why organisms are more likely to cooperate with some individuals than others

A global research team has built five new synthetic yeast chromosomes, meaning that 30 percent of a key organism's genetic material has now been swapped out for engineered replacements. This is one of several findings of ...

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

See the article here:
Biology team makes breakthrough in synthetic yeast project - Phys.Org