The 2018 Yeast Genetics Meeting (#Yeast18) was held in August at Stanford University in Palo Alto. I learned about the latest developments in research and advances in tools and technology, reconnected with former colleagues, and established new connections and potential collaborations. It was also great to finally meet our PMM2 PerlQuest collaborators, Greg Lang of LeHigh University, and his grad student Ryan Vignona, as well as some of the scientists that I had been following on Science Twitter.
Ready, set, yeast!
2018 Yeast Genetics Meeting highlights
There were far too many great talks at the 2018 Yeast Genetics Meeting to cover in one blog post, so I will highlight only a few that relate to yeast as a human disease model.
Christopher Loewen of the University of British Columbia described his lab’s effort into the Sentinel Interaction Map. Many clinical sequence variants of human genes are not known to associate with any diseases. Sentinels are yeast mutants that are sensitized to over-expression of a human gene. They can be used to determine how functional a given sequence variant is. For example, say that we over-express a wild type or normal human gene variant in yeast and it kills the cells. When we then over-express a sequence variant of the same gene, the yeast cells continue to grow. This tells us that this variant is not functioning normally. What is great about this tool is that these genes do not need to be conserved in yeast! They only need to have an effect on the growth of yeast cells when we over-express them. This expands our ability to use yeast to understand human gene variants.
2018 Yeast Genetics Meeting swag
Anita Corbett of Emory University described yeast models of EXOSC3 and EXOSC2. These are subunits of the RNA exosome complex, which was originally identified in yeast. Mutations in conserved residues of EXOSC3, EXOSC3, as well as other subunits of the exosome EXOSC8 and EXOSC9 cause diseases. EXOSC3 mutations specifically link to a rare disease in humans called Pontocellubellar Hypoplasia. Analogous mutations in the yeast EXOSC3 and EXOSC2 cause a temperature sensitive phenotype, which indicates a protein stability defect. She extends this further by characterizing EXOSC3 mutations in fly models. Similarly, the fly models show morphological defects and partial effect on viability. This is not surprising, but it is reassuring to see conservation across organism. Corbett also showed a nice diagram pointing out the application of model systems to human diseases. In particular, although flies and yeast may be further away from showing the human disease phenotype, we can learn a lot about the mechanism and function (or dysfunction) of a gene variant that would be more challenging in cell culture or mouse models.
Benoit Kornmann of ETH Zurich described improvements to our understanding of conditional essential genes – that is, genes that become essential under specific condition(s). This isn’t yeast as a human disease model exactly, but it’s a powerful tool to understand the relative importance of a gene that I think will facilitate yeast model development. The yeast community has long been aware of genes that are essential for growth under all conditions. Using saturated transposon insertion combined across different growth conditions, Kornmann was able to identify genes that are essential under specific conditions on a genome-wide scale. Furthermore, the method is high resolution and can detect gain-of-function mutations. For example, if the transposon knocks out a regulatory domain like the nuclear localization signal, this could lead to a case where the gene is constitutively on and this can affect cell growth.
More yeast swag
I also spoke to Anita Manogaran of Marquette University, and her undergraduate student Emily Davis, about their yeast model of Transthyretin amyloidosis (ATTR), an age-related disease. ATTR is associated with the accumulation of amyloid that results from the aggregation of the Transthyretin proteins. Expression of Transthyretin in yeast also leads to amyloid-like protein aggregates, suggesting that yeast could be a good in vivo model for ATTR.
The 2018 Yeast Genetics Meeting was very fulfilling, both personally and professionally, and I look forward to the next time I get to gather with this group of yeast researchers. The next meeting, however, won’t just be a yeast meeting. It’ll be The Allied Genetics Meeting 2020, with all the genetic model organisms, in Washington, DC!
BTW, I’m collecting #yeast jokes for possible appearance on some fun new pages in development on Perlara’s website. What are some of your favorites? Leave ’em as a comment below or reply to my request on Twitter. Remember to follow me @jessplao and @PerlaraPBC too!
Like yeast? Read about Perlara’s work in developing various disease models in yeast.