Feature: Blending ‘omics in the wine glass

This feature appeared in the November/December 2009 issue of Australian Life Scientist. To subscribe to the magazine, go here.

For thousands of years, winemakers have been breeding new varieties of grapes, applying different strains of yeast and experimenting with techniques to incrementally improve flavours, yields and develop the spectrum of wines you can find at your local bottle shop today. Even now, winemaking follows many of the same customs in what is essentially a sophisticated version of trial and error. But times are changing.

After all, when you take a sip of that ruby red Barossa shiraz, you’re really tasting the combined metabolome of the grape, yeast and bacteria present in fermentation. That doesn’t sound quite as romantic as saying it has peppery notes with a cheeky finish, but this scientific approach is set to fundamentally change the way wine is made.

At the forefront of wine research is the Australian Wine Research Institute (AWRI), based in South Australia, not far from the famed winemaking region, the Barossa Valley. The AWRI has been in operation for more than 50 years and is primarily funded by Australian winemakers and grape growers, along with funding from Australian Government, through the Grape and Wine Research Development Corporation.

The AWRI is currently undertaking an ambitious project to gain an unprecedented insight into the ubiquitous wine yeast, Saccharomyces cerevisiae. This project will not only contribute valuable knowledge to the commercial wine industry, but is also serving as the vanguard for an even greater endeavour – a new approach to studying biological processes: systems biology.

Bottom-up, top-down

“The traditional way we do research in biology is to approach things as a collection of component parts; we take a reductionist approach,” says Paul Chambers, Research Manager for Biosciences at the AWRI. “It’s been a very powerful approach to date. Most of what we know in molecular biology and genetics comes from these reductionist approaches, understanding one or two genes at a time, one or two proteins at a time.

“The problem is that sometimes when you go back to the whole organism with what you’ve learned about the isolated component parts, it’s more complex. The component you’ve been looking at perhaps interacts with components you’d never have guessed. It might be involved in processes other than the ones you’ve been focused on.”

The alternative is to turn this approach on its head. Instead of looking at a small number of isolated components, you explore the complex interactions between all components in the organism.

---PB---

“Systems biology attempts to look at the whole mix of components in single experiments so you can see what collection of genes might be involved in a particular trait, or what collection of proteins might be important in the cell, or what metabolic pathways might be up or down regulated. You start looking at the complexity of biological system rather than looking at single components or small numbers of components.”

Systems biology brings together a wide range of disciplines, from genomics up through transcriptomics, proteomics, metabolomics and fluxomics, and knits them all together using sophisticated bioinformatics technologies. Weaving all these disparate disciplines together is clearly an ambitious venture, and it’s for this reason that when the Australian Government-sponsored Bioplatforms Australia wanted to kick start systems biology in Australia, it chose as a model organism one of the simplest and best understood that we have: the wine yeast Saccharomyces cerevisiae.

Wine fermentation also provided an ideal test bed for systems biology due to its relative simplicity, at least in biological terms. “Compared to human cells and cancer or mouse cells and the immune system, wine yeast fermentation is relatively simple,” says Chambers.

As a result the AWRI is working with Genomics Australia, Proteomics Australia, Metabolomics Australia and Bioinformatics Australia, all overseen by Bioplatforms Australia, to conduct this pioneering study in systems biology in Australia.

“We’re very excited about this because we’re getting this really big science approach to Australian wine research that would typically be out of our reach,” says Chambers. “Also we’re very happy that our system is being utilised to do some trailblazing to get systems biology projects underway in Australia in a meaningful sense. And, of course, any outcomes from this will be of direct benefit to a major Australian industry.”

Microbiological characters

Yeast plays a central role in the process of wine fermentation, and the choice of yeast can radically affect the final product. “There’s a couple of hundred different commercial wine yeast strains available to wine makers today,” says Chambers. “Those wine yeasts have quite different properties and they’ll deliver quite different outcomes for wine makers. Some wine yeasts are particularly good at bringing out fruit characters or floral characters in wine, others will not emphasise those characters as much and will bring out other qualities.”

The greater understanding of yeast that will emerge from the systems biology project will enable the development of new and improved yeast strains that will add to the arsenal available to wine makers, allowing them to better control the outcome of their wine making process.

---PB---

However, there’s another reason to develop new yeast strains beyond their impact on the characters present in the wine. Over the past few decades, the alcohol content in wine has been creeping steadily upwards. “In some parts of Australia, you get lots of sunshine, and the grapes are left on the vines to develop those big lovely rich aromas and flavours are typical of many Australian wines. The problem with that is that you end up building up a lot of sugar in the grape. The yeast cell then takes just about every molecule of sugar it can get and it makes alcohol from it.”

This escalating level of alcohol has some negative consequences. One is the health impact, with the World Health Organisation recently putting pressure on governments around the world to make efforts to reduce alcohol consumption. Another consideration is that high alcohol content can actually negatively impact the flavours in the wine itself. “We know that if the alcohol levels get too high in wine, they can deaden some of the flavours. So you can actually compromise the quality of the wine if the alcohol levels are too high,” says Chambers.

“What we would like to do is try to manipulate the metabolism in wine yeast so that it will make less alcohol from the sugar it consumes. As alcohol is an important contributor to many aspects of the taste and mouth-feel of wine, our aim is to just get the alcohol levels down a little, not to completely remove it.”

And according to Chambers, the systems biology approach lends itself to these objectives nicely. “We think that systems biology is going to give us a much more informed approach to things like metabolic engineering in a wine context,” he says. “Currently, we manipulate the yeast we work with to get particular traits. Sometimes when we do that we end up with a yeast that might perform in less optimal ways. It might produce flavours that are less than desirable, it might be less robust than it needs to be to work in wine fermentation. We’re hoping that by moving down the path of systems biology we’ll be able to look at the complexity of the genetic and biochemical systems in the cell and make more informed decisions on how to manipulate metabolism to get the outcomes that we want.”

‘omics and ‘omics of data

One of the major hurdles to overcome in a systems biology approach is weaving together multiple layers of ‘omics in to one unified result. “Data management is a major issue,” says Chambers. “There are massive amounts of data generated in our experiments. And we’re still to work out how we’ll integrate the data sets. One of the issues we might face is that the data sets from the different platforms are quite different to each other. There might be issues of compatibility that we’ll have to iron out in the coming months. I think that’s going to be quite interesting.”

Communication is also a challenge, particularly between the scientists producing the data, and the bioinformaticians knitting it all together. “It requires informaticians and biologists to communicate with each other, and they often come from quite different worlds. Both sides find it a little difficult to understand where the others are coming from. That’s a cultural and language divide that we’re trying to bridge, and I think we’re doing okay, but it is slow. I suspect that’s going to be one of the most interesting aspects in terms of building a project and getting the systemic side of the project sorted out.”

Another challenge is that, by its nature, systems biology is interdisciplinary, yet there are few, if any, researchers who are intimate with all aspects of all the disciplines involved. “It’s quite difficult to plan a project when you don’t really know the different components of it yourself. And there aren’t any people out there who know how to do all the components. We do really rely on communication and cooperation and collaboration. These projects absolutely require good communication and a willingness to cross collaborate. That sounds a bit airy fairy, but there’s no other way it can work.”

---PB---

Clean finish

Since the project got underway in January of this year, progress has been steady, with the AWRI researchers laying the foundations for the greater systems biology programme. The first few months were spent establishing the model fermentations that will be used to experiment with the wine yeasts throughout the project. To do this, they also needed an improved synthetic grape juice that suited their needs, as real grape juice is too wildly variable to be reliable in repeatable experiments.

That accomplished, the first experimental fermentation using Saccharomyces cerevisiae was finished in late September, with a replicate run completed several weeks later. All this is just to ensure that all the systems and methods are in place to act as the foundation for further experiments, which will kick off later in the year.

The three-year goal is to be able to develop wine yeasts that produce less alcohol but, crucially, also produce high quality wine and which are robust enough to handle the rigors of commercial fermentation. “If all that works well we hope we’ll be in a position to take some low alcohol wine yeasts out to the industry in around four to five years. Longer term, when we’ve got all of the ground work done, we want to use this approach to look at developing what we call flavour active yeasts – yeasts that will coax amazing flavour out of the grape juice and give complexity and intensity to wine.”

But the results won’t only impact the wine industry. Yeast is also a crucial component of other industrial processes, from brewing beer to the production of biofuels, and Chambers expect the results of the AWRI’s systems biology project to benefit these industries as well.

Then there’s the scientific benefits of forging a path in to the uncharted realm of systems biology, which is set to fundamentally change the way we approach biology. “It’s an exciting time to be doing biology. Most biologists have had the sense that we’re working with these amazingly beautiful complex systems, and we don’t do justice to them necessarily with the reductionist approaches,” says Chambers. “We do our best, and there have been some incredible developments and discoveries from the reductionist approach, but it’s exciting to think that now methods are available to us that are allowing us to knock on the door of that complexity and begin to open the way to new understandings of biological systems.”

And in the process we get even better wine. It’s hard to question the benefit of that.