Dr. Neuvéglise: – Yeast is a fascinating research model

Yeast – the average person associates it with sweet rolls and wine, but that’s just a fraction of its potential. What do we know about yeast, and what’s still left to discover? What has surprised you about it?

Yes, indeed, yeasts have enormous potential. There are thousands of yeast species, each with unique traits and uses. Baker's yeast Saccharomyces cerevisiae is the best known, but others find roles in white biotechnology as cell factories, in various fermented foods, and even in dietary supplements. Yeasts provide many ecosystem services. They help decompose organic matter, recycling nutrients back into the ecosystem. Yeasts have been the basis of many discoveries and the number of Nobel Prizes testifies to the importance of this eukaryotic model. There’s still a wealth of knowledge waiting to be discovered: new species and genera, new metabolic pathways, and new gene functions, with potentially unknown properties. The future of yeast research promises exciting discoveries about diversity (there are still unexplored environments), metabolic properties other than fermentation with potential new applications, or human health. The intricate relationship between yeast and our gut microbiota is a fascinating area to explore.

Is yeast a demanding research subject, or does luck play a role in researching it?

Yeast research is a fascinating mix of demanding rigour and a touch of chance. Experiments in yeast require careful control. Because experiments are usually performed on a population of cells, small variations can occur and their significance must be carefully analysed, not over-analysed. Moreover, although S. cerevisiae is a well-known model, some metabolic pathways are not fully understood and depend on others. Sorting out the meaningful results is sometimes a real challenge.

But unexpected discoveries can be made, especially in non-Saccharomyces yeasts. I think studying yeast biodiversity is more likely to lead to novelties.

How have biotechnology and bioinformatics advanced yeast research?

Yes, we can say that biotechnology and bioinformatics have revolutionised yeast research and accelerated discoveries. The sequencing of S. cerevisiae that was completed in 1996 has provided a wealth of data, with enormous consequences for the identification of genes, their putative function, and the understanding of chromosome structure. Then the Génolevures consortium coordinated by B. Dujon, J.L. Souciet, and C. Gaillardin, opened the way to comparative genomics. That was 26 years ago and now, with the development of bioinformatics tools, anyone can sequence and (automatically) annotate the genome of their favourite species or strain, even without any skills in genomics, which is probably why the gene databases are full of errors!

The next step has been the development of in silico modelling, which makes it possible to simulate yeast behaviour and predict outcomes under different conditions. This allows for faster and more cost-effective experimentation prior to experimental trials. In the laboratory, genetic engineering with techniques such as CRISPR-Cas9, TALEN, and Gibson assembly have revolutionised previously time-consuming experiments. High-throughput is now commonplace in all laboratories with the drawback that it significantly increases the cost of experiments.

You conduct research on the biological diversity of yeast genomes in various environments, particularly in viticulture. Southern Europe is synonymous with winemaking, but lately, dire warnings about climate change have reached the general public – climate change could destroy viticulture. Droughts and excessively high temperatures, along with shorter growing seasons, might lead to the end of wine production. From your perspective, do yeast have any special adaptive abilities to the changing conditions they live in?

No, to be honest, we can’t say that climate change will destroy viticulture. Wine production still has many good years ahead of it. Alternatives are being developed with new grape varieties that are tolerant to higher temperatures or resistant to cryptogamic diseases. These are mainly hybrids between Vitis vinifera and other grape varieties that contain genes of interest (e.g. resistance to mildew and powdery mildew). The selection of low-sugar varieties also makes it possible to keep the alcohol content at a reasonable level. It is true, however, that climate change is a threat to yeast diversity. Last year in vineyards near Montpellier, we observed a dramatic reduction in fermentative yeasts on the grapes. This has many consequences for spontaneous fermentation, i.e. with the only microbiota present on the grapes, without commercial inoculum. Experiments are underway to find alternatives. We are studying the ability of fermentative yeasts to survive at high temperatures through adaptive laboratory experiments.

Beyond the food industry, what other uses does yeast have for humans?

Yeast potential extends far beyond wine, beer, bread and other fermented foods. They can be used in health and medicine, such as Saccharomyces boulardii, which is used as a probiotic. Yeast-derived enzymes are also used in various medical applications. We can also cite the case of yeast used as cell factories to produce specific antigens, which are crucial components in vaccines for diseases such as Hepatitis B. 

Yeast as a cell factory is used in white biotechnology, which has many fields of applications: production of biofuels (bioethanol or biodiesel), biodegradable plastics, and biosurfactants, i.e. alternatives to chemical detergents. The idea today is to explore the possibility of using renewable sources for more sustainable alternatives to traditional petroleum-based products. In addition, yeasts can help to clean up polluted environments by hydrolysing pollutants consisting of heavy metals or organic compounds.

What sparked your interest in yeast?

To be honest, I had just finished my thesis on the use of an entomopathogenic fungus to control sugarcane whiteworm and I wanted to continue working on fungal diversity. At the INRA, there was a permanent position on yeast diversity using a genomic approach. I was immediately very interested. And there you have it, almost 30 years later, I still believe that yeasts are the best biological model for scientists!

You collaborate with scientists from the Wrocław University of Environmental and Life Sciences – when did this collaboration begin? What determines its character or uniqueness?

My collaboration with scientists from the Wrocław University of Environmental and Life Sciences started at least 12 years ago when Prof. Małgorzata Robak visited our team in Thiverval-Grignon. She invited me to give a lecture in Wrocław in 2014 and to organise a training course in yeast genomics in 2016 and 2017. In 2012, she recommended her PhD student and we hired Zbigniew Lazar for a two-year postdoctoral position. This was the beginning of our collaboration on Yarrowia lipolytica, which is still ongoing. Also in 2014, Dr. Xymena Połomska, went to our lab in Thiverval-Grignon to purify plasmids of Debaryomyces hansenii and together we received a PHC Polonium grant to work on the killer toxin of D. hansenii. Then, several Polish students from different teams came to our lab with different projects on Y. lipolytica or D. hansenii.

What does scientific work mean to you?

In my view, scientific work is a never-ending quest for better knowledge to understand a particular question, to formulate hypotheses and to test them experimentally. It’s a collaborative effort, building on past discoveries and looking to the future with new questions, in the hope of making discoveries that will change and if possible improve our lives. It means being rigorous, creative, critical, honest, and able to share results with the international community. True collaborations are not always easy to get, as scientists are often competitive. But, when it is, it's so much more rewarding. This is how I see my collaboration with Prof. Zbigniew Lazar. 

How do you evaluate the role and position of women in science – what has changed or is changing in recent years? Universities are undertaking equality initiatives, but does true equality or parity exist, even in France, where the scientific icon is, after all, Marie Skłodowska-Curie from Poland? Skłodowska-Curie had to leave Russia since historically Poland did not exist at the time, because as a woman she could not study or work in science. In France, the Sorbonne graduate, double Nobel winner, was not admitted to the French Academy of Sciences.

It is clear that it has been much more difficult for a woman to be a scientist in the last centuries. Marie Skłodowska-Curie was not accepted into the French Academy of Sciences but was recognized as a true scientist. On the opposite, the studies carried out by other women were deliberately ignored because they were too far beyond the understanding of their time. I often think of Barbara McClintock who discovered mobile genetic elements even before the structure of DNA was known. It took almost 40 years for her to be awarded the Nobel Prize. I think life is much easier for women in science today. In biology in France, I would say that there is now parity and women have access to senior positions. This was not the case almost 30 years ago when I joined the INRA. All the team leaders and the head of the unit were men!

Should a scientist also teach? How should one combine research with teaching? How can one be a master, mentor, and role model?

Yes, I think so. Scientists should teach, but not too much! Teaching is very time-consuming and exhausting. I think 300 hours a year is simply impossible! Being a scientist-teacher is beneficial for the students and for the scientists. On the one hand, it is a way of bringing fresh insights and enthusiasm to the students, a way of creating vocations. On the other hand, the scientist has to learn and be aware of everything about his or her domain of expertise, which is not always the case when scientists are too specialised.

When you’re not working with yeast, you are... doing what?

I’m drinking them!

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  The EU GREEN alliance meeting of rectors is underway

  A strategic meeting of the rectors of the EU GREEN alliance – Board of Rectors– which includes nine European universities, has begun at the Wrocław University of Environmental and Life Sciences in Wrocław. This event is of crucial importance, taking place twice a year, during which the future development path of the international partnership is determined.