SINGAPORE: Scientists from the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine), have successfully synthesised a redesigned yeast chromosome XV, consisting of a staggering 1.05 million base pairs. This marks the largest synthesised chromosome in Asia and a significant leap forward in the field of synthetic biology.

Yeast, renowned as a model organism for comprehending basic cellular processes, shares cellular similarities with plants and animals. Its simplicity of manipulation and study make it an invaluable tool for scientists. The redesign and synthesis of the yeast genome, specifically chromosome XV, provide a unique opportunity for researchers to unravel the impact of genetic variations on individual traits, potentially shedding light on the mechanisms of genetic diseases.

The driving force behind this scientific feat is Associate Professor Matthew Chang, who leads a team as part of the Synthetic Yeast Genome Project (Sc2.0). This international consortium unites labs worldwide in an effort to redesign and construct all 16 yeast chromosomes from scratch. A/Prof Chang’s team’s accomplishment is hailed as a major milestone in the realm of synthetic biology.

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Creating the synthetic Chromosome XV (synXV) involved a comprehensive redesign of the original DNA, resulting in a sequence distinctively unique from the natural one.

The team introduced a groundbreaking technology, CRISPR/Cas9-mediated mitotic recombination with endoreduplication (CRIMiRE), to streamline the assembly process of synXV. This innovative technology accelerates the exchange of large chromosomal DNA segments at specific sites, facilitating the concurrent assembly of multiple synthetic chromosome segments into a complete synthetic Chromosome XV. The details of this pioneering work are published in Cell Genomics.

CRIMiRE simplifies the process and allows intentional mixing and matching of synXV with another yeast chromosome, generating various genetic combinations for studies. This approach offers a deeper understanding of the association between genetic variations and individual traits.

Associate Professor Matthew Chang said, “This achievement opens the door to understanding basic questions about biological processes.” He highlighted the remarkable journey of constructing the synthetic yeast chromosome and emphasized the team’s ability to rapidly reconfigure them for further studies, unlocking answers to fundamental biological questions.

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Dr Foo Jee Loon, Research Assistant Professor from SynCTI, Syn Bio TRP, and the Department of Biochemistry, NUS Medicine, and the paper’s first author, asserted this work’s promise for future advancements in synthetic genomics.

The ability to work with larger and more complex chromosomes holds the potential to decipher mechanisms and understand genetic diseases better, potentially paving the way for revolutionary treatments.