Using yeast to untangle the complexity of life


At our headquarters set in the beautiful UK countryside, Singer Instruments were honoured to welcome world-leading yeast geneticist Professor Joseph Schacherer along with team member Teo Fournier, from the University of Strasbourg.

They arrived hot on the heels of their Nature paper – a game changer in understanding the natural genetic and phenotypic diversity of yeast populations globally. We were keen to hear the story behind the paper and show Joseph and Teo around the factory where some of the robots helping drive their research are manufactured, built and tested!

The challenge

Uncovering what’s behind the awesome phenotypic diversity seen in nature is one of biology’s greatest challenges. The 1002 Yeast Genomes project was a ground-breaking effort in that regard, setting out to map the total phenotypic variation of the Saccharomyces cerevisiae genome on a global scale. It was a challenge of epic proportions so we were keen to ask the pair what motivates their science?

At the project’s inception in 2013, yeast population genomic studies had been limited to a small number of isolates (less than 100 strains). Together with Gianni Liti and Genoscope, The Schacherer group co-founded a mission to take that figure to more than 1,000 yeast isolates sourced from a wide variety of different ecological and geographical backgrounds.

Joseph knew the task would be enormous: “It’s easy to get a thousand wine strains, but that’s not how we wanted to proceed,” was his candid response to The Atlantic when asked why they went to such lengths to uncover little-known wild strains from far flung corners of the world.

Equivalent large-scale programmes had already been accomplished in Arabidopsis thaliana and humans, but this was the first attempt to address a eukaryotic model system in such meticulous detail. However, Joseph had clearly been under no illusion about the scale of the undertaking:

“In our work we’re trying to find genomic regions that are related to some specific phenotype. Sometimes you get lucky and find a single region that is strongly involved in a trait. But often it’s more complex than that, requiring high throughput experimentation and data analysis, and making those interesting discoveries a much longer process.”

The solution

Fortunately for Joseph’s team, working in yeast meant 1002 genomes had several advantages over its forerunners in Arabidopsis and humans. Not least, the genetic manipulation of yeast is cheaper and significantly easier than more complex multicellular organisms, as Joseph explains:

The team also had access to the fastest colony manipulation robot in the world, capable of accurately and reliably arraying nearly a million colonies per hour! We are of course referring to Singer Instruments’ ROTOR+ which, when combined with rapidly advancing next-generation sequencing technology, was able to shave not months but years off the time needed to complete the project. In fact, 1002 genomes achieved journal publication up to three years quicker than its 2008 predecessors, the 1000 genomes and 1001 genomes programmes. Put simply, Teo told us:

“For scalability and high throughput the ROTOR has allowed us to phenotype thousands of strains, which otherwise would not have been possible.”

Not long after the publication of their landmark paper, Joseph and Teo chose to add ‘PIXL’ to their microbial handling arsenal, an ultra high precision colony picker. PIXL and ROTOR+ combine to perform almost seamless end-to-end high-throughput screening workflows. It gave the team the efficiency and reliability they needed to continue the legacy from 1002 genomes, and move their experiments “from the micro to the macro”, says Joseph:

“We now have a new challenge that we think […PIXL] will be able to help solve. We have generated many segregants from crossing different isolates and what we want to be able to do now is handle them individually. We can achieve this with toothpicks but it’s time-consuming and also a source of error and so PIXL is going to be much better for us in many ways.”

Two years on, we caught up with Joseph and his team in the lab to see how it’s going and shot this short video:

A final word…

A responsibility to science’ is more than a tagline for Singer Instruments. It’s a guiding principle that drives product development and ensures great service and technical support. Professor Schacherer added his own views:

Professor Joseph Schacherer
Laboratory for Molecular Genetics,
Genomics and Microbiology (GMGM), University of Strasbourg

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