Sanger embraces new approach to genomic research

The Wellcome Sanger Institute has embarked on a new field of research - synthetic genomics - by working with three of the area's leading scientists. Tom Ellis, Jason Chin and Patrick Cai have joined the Sanger as Associate Faculty and will establish small research teams at the Institute to lay the foundations for creating and inserting synthetic DNA sequences into genomes at speed and scale. The ultimate goal is to develop the methods needed to build an entire working genome from scratch.

Their work will open new avenues of understanding how different stretches of DNA play key roles in determining health and disease by affecting how genes are switched on and off, and why.

Patrick Cai is the Chair Professor of Synthetic Genomics at The University of Manchester, developing methods to support the creation of a completely artificial yeast genome and to then evolve new and useful functions within it by using recombination techniques. In addition to working with yeast cells, Patrick has also devised a one-pot, overnight system to deliver long sections of DNA into mammalian cells using an approach known as EMMA (Extensible Mammalian Modular Assembly).

At the Sanger Institute, Patrick's Associate Faculty team will be looking to scale up the EMMA system to an industrial level using computer-aided design and automation. The goal will be to create a way of introducing biological pathways and protein products into cells that can reveal changes in a cell's state (to show how genes' actions affect cell state), introduce missing components to diseased cells and even create new biological pathways in the cell that respond to internal or external cues.

Patrick's group will also work with other Synthetic Genomics Associate Faculty teams to use synthetic genomes to find targets for drug sensitivity, explore how much of a genome needs to be changed for a new species to appear, and build and test a synthetic mitochondrial genome in yeast.

Not only will this work create a highly adaptable model with which to test gene functions, and even add in useful abilities - such as breaking down oil spills - but the journey itself will reveal more about the structure and workings of genomes. By only using the DNA needed to make a working genome, researchers will discover which segments of DNA between genes have vital roles to play, and what those roles are.

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