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Q&A: AgriBio Researchers on the Application of a Systems Biology Approach to Agriculture

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Name: Ben Cocks
Position: Research Director, Biosciences at Victorian Department of Primary Industries; Professor Animal Genetics and Genomics at La Trobe University
Background: Senior Director, Drug Discovery Biology at Incyte; PhD Biochemistry, University of Melbourne

Name: Simone Rochfort
Position: Principal Research Scientist, Biosciences at Victorian Department of Primary Industries
Background: Research Scientist, Mass Spectrometry at Victorian Department of Primary Industries; PhD Marine Natural Products Chemistry, University of Melbourne

The Biosciences Research Division of Victoria, Australia's Department of Primary Industries is applying a systems biology approach, including proteomic and metabolomic techniques, to improving agricultural profitability and sustainability in Australia and worldwide.

In May 2009, the Victorian government and La Trobe University began work on a new facility to house the organization's research – AgriBio, the Centre for AgriBioscience. The A$288 million ($256 million) facility is scheduled to be fully operational in 2012 and will accommodate up to 400 staff including researchers, students, and support staff.

This month, Thermo Fisher announced that it would be outfitting the facility with AU$2.5 million in mass spectrometry equipment, including two LTQ Orbitrap Velos machines.

Ben Cocks and Simone Rochfort are scientists at AgriBio with joint appointments at DPI and La Trobe University. This week they spoke to ProteoMonitor about their research and the goal of applying systems biology to agricultural production more generally.

Below is an edited version of the interview.


How established is the practice of applying proteomics to agriculture?

Ben Cocks: The history of proteomics is that in mammalian systems like mice and humans it's been well established as a useful technology for discovery. In mammalian systems such as cows it's just as effective, but the application of the technology in agricultural animals is behind, I guess, what it's been for investigations in diseases such as cancer. But all the relevant pathways to do with, say, lactation and muscling as two examples, can all be investigated very effectively with the new proteomics tools.

What sort of pathways are you investigating and what are their potential applications?

BC: The main ones for us are really focused on dairy animals and that means looking at processes important for feed conversion efficiency and also in lactation. We are looking to get [proteomic] profiles and [an] understanding of what makes superior animals. We're also using the technology to understand some of the fundamental cell biology. The ultimate aim would be to have some kind of profiling that would assist with genetic tests, improving productivity. There are about 40 different traits that are selected for genetically, and what we are looking to do is understand the genetic variation that leads to the economic phenotypes.

So this is being done with commercial applications in mind?

BC: Yes, that's definitely the aim. So in the muscling example, it's enabled us to understand some of the pathways involved in muscling in animals and therefore has assisted in the genetic selection and also assisted with management approaches to increase muscling.

How does it apply to management for muscling?

BC: With feed modification. In our case it's more about a specific additive that we can use to activate certain pathways that we understand. Of course, at that point it really isn't about proteomics. Proteomics is one part of the systems biology puzzle [we use] to understand muscle biology.

So it's a whole systems biology approach to agriculture?

BC: Yeah, I think that's probably where we are fairly unique as far as we know in terms of being able to combine the genomics approach, metabolomics, proteomics, and transcriptomics in a systems biology context to understand animal and plant systems.

Have any commercial applications come out of this so far?

BC: I guess probably the big success story we've had is we've greatly assisted milk processing companies by being able to determine what proteins are in milk and in different milk fractions. The techniques allow you basically to detect every protein that's in milk. There are higher value milk fractions, so this allows companies to determine what proteins are going into what fractions, and it allows them to identify bioactive components, for example, to develop as new products.

Milk components are used for everything from baby formula through to complementary medicines. There was knowledge of what was present in terms of the most abundant proteins, but without really knowing what some of the more mid- to lower-abundance proteins were in the mixture. It turns out these were critically important components. One example would be lactoferrin. Lactoferrin is a protein that's more abundant in human milk than in bovine milk – it's an antimicrobial protein – and what the dairy companies actually do is purify lactoferrin from bovine milk and add it to infant formula. That's one example.

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What other areas of research are you looking at?

BC: One of the things that we're very interested in is the microbial populations, for example, in the rumen, and we've been using some metabolomics in that area and are starting to look at the interaction between the mammalian system and the microbial communities – what proteins are made by the host, and what are the protein components of the microbial population. The main aim there is to increase feed conversion efficiency in dairy cattle and also to reduce methane emissions by ruminants.

We're in fairly early stages in that area. We've definitely developed more genomics tools to give us some leads in that area. One other area that the proteomics is useful for us is characterizing proteins that we express. If we're doing expression in E. coli we can quality control the proteins that we're making. To validate the role of some proteins we identify in systems like muscling and lactation we'll make certain proteins to test them, mostly in vitro, to validate their involvement in certain processes.

Simone Rochfort: One of the major [projects] at the moment is in the area of forage improvement, particularly in the area of rye grass endophyte interaction. Rye grass is a major forage here and also in New Zealand, and [it has] these endophytes in [it] that produce alkaloid compounds. Some of these metabolites are good for agriculture in that they seem to help with stress, drought tolerance, and insect resistance, but other metabolites that these endophytes can produce are toxic to animals and so you get something known as rye grass staggers. So our aim is to produce new endophyte varieties that are stable in the plant that produce the beneficial but not the toxic alkaloids. We've been working on that for about four years.

Some of the other work we're doing in terms of forage improvement includes looking at metabolic pathways that produce lignin and saponin as well as condensed tannins. To improve the digestibility is the overall end. If we can alter the lignin structure, for example, we might be able to increase the digestibility of the forage and that will mean we get better feed conversion efficiency from the animals. We've come up with some interesting strains of the rye grass and also some interesting white clover products as well in terms of viral resistance and condensed tannins biosynthesis.

So it's really looking at both the systems biology of the individual animals and the larger agricultural system?

SR: Absolutely. We're looking at the farming system, if you like, and trying to optimize it from all aspects that we can think of. Hence the forages and the rumen and the animal work that we do.

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