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Q&A: Danforth's New President on Computational Expansion Plans and the Challenges of Plant Research

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JimCarrington.jpgJames Carrington — a professor of botany and plant pathology and the director of the Center for Genome Research and Biocomputing at Oregon State University — will take the helm as the new president of the Donald Danforth Plant Science Center on May 1.

As the director of the CGRB, Carrington was involved in campus-wide efforts in computational and genomic biology research and education, and his background in computational biology will play a large role in his new position. The Danforth Center recently received a $70 million grant from the Danforth Foundation to expand its staff and facilities, with a particular emphasis on its bioinformatics and biocomputing capabilities.

As the new head of the Danforth Center, Carrington will be in charge of more than 200 employees and a $20 million annual budget. Investigators at the center conduct research into areas such as biofuels, biofortification, disease resistance, drought tolerance, pesticide and fertilizer reduction, and biosafety and regulation.

Prior to joining the faculty of OSU, Carrington served as a professor at the Institute of Biological Chemistry at Washington State University, and spent nine years as a biology professor at Texas A&M University. He is also a member of the National Academy of Sciences.

Carrington's research areas include gene silencing, the functions of small RNA, and virus-host interactions. He received his BS in plant science from the University of California, Riverside, in 1982 and his PhD in plant pathology from the University of California, Berkeley, in 1986.

This week, BioInform spoke with Carrington about Danforth's growing plans as well as the informatics challenges of the plant science space. Below is an edited version of the conversation.

Your appointment was approved last November, but your term officially begins on May 1. What have you been up to in the intervening months?

A lot of the work that I am doing has to do with recruiting new people. We are going to be bringing in about five new people and the search for those people has been going on for the past few months and we are interviewing candidates now. Other things involve setting up some agreements and cooperative interactions with neighboring institutions such as Washington University in St. Louis.

What positions are you looking to fill at Danforth with the new hires?

We are looking for people addressing important problems in plant science. That can be at any level but we are particularly interested in people who are using computational systems [and] synthetic or genomic approaches to solve these big problems. We are looking in particular for people who are integrative, who can span from the computative to the biological, and we are looking for those people to integrate well with the mission of the Danforth Center, which is to serve humanity through plant science.

We are hoping that the new faculty would have an interest in things like biofuels or crop improvement or other areas, even though they may be working on a fundamental problem in plant biology. So there is lots of room for collaboration and interaction from the basic science to the translational science.

You mentioned a partnership with Washington University. Can you give some details about that and other partnerships you are looking to form?

There are partner institutions that the Danforth Center has maintained since the center was founded and that includes Washington University, the University of Missouri, and the University of Illinois. Some faculty at the center have adjunct appointments at these partner institutions.

But then there are some new interactions that we are developing now with the genome scientists and the computational and systems biologists. For example, with the Center for Genome Sciences and Systems Biology at Washington University — that's headed by Jeff Gordon — we are setting up collaborative agreements whereby we would interact with their scientists, instrumentation, and computing facilities to do the work at the Danforth center.

The Danforth Center [also] has a very productive arrangement with the [US Department of Agriculture] whereby we house a couple of their scientists and they interact as faculty within the center but they are USDA employees.

The center recently received a $70 million grant from the Danforth Foundation. What are your plans for the funds as well as for the Danforth Center in general?

Those funds will enable us to hire this new round of faculty and to get the center's facilities up to full capacity. The funds will support the expansion of computational core facilities and computational expertise. As you know, all areas of modern biosciences, including plant science, is heavily dependent on quantitative science — in particular, computation, statistics, and mathematics — and so we need to develop more capacity and facilities to support those areas. The funds will [also] enable expansion of support to graduate students at our partner institutions.

Let's talk a little bit about the computational aspect of your expansion plans

There are a lot of areas that require advanced computation — high-throughput genomics and high-throughput genome expression analyses, comparative genomics, also proteomics and association mapping. All of these types of approaches to answer fundamental questions or applied questions in plant science require computation. So on the data acquisition side and analysis of primary data, there is a big need for not only computation but also statistics, mathematics, and eventually modeling once we are to the point where models are useful to us.

What that means is that groups that have good computational biology or quantitative talent in the form of faculty, staff, and students are at a real advantage. This is why we are so interested in developing additional core competence and hiring additional faculty who have a heavy computational and quantitative component to their research.

Following up on that, are you looking to focus on developing tools in-house or are you considering commercial and open source products?

Bioinformatics and computational biology has really developed in the open source computing world. Most of the tools that are developed to answer questions that involve high-throughput data have been developed in academic labs and they're available as open source tools. So the culture in biocomputing is very much open source and we anticipate continuing that.

There is a lot of room, however, for specific collaborations with people, prior to the open source tools being made open to the public. This is where the interaction with the Center for Genome Science and Systems Biology will be very important because they have some of the best computational minds in the world there and we hope to tap into their expertise and their talents and gain from their experience.

That means most of the collaboration will occur [around] new technology for computing, which will mostly involve tool development, algorithms, and other software type tools.

Are you planning to purchase any hardware?

We'll purchase some. But again, the center at Washington University has a very significant compute cluster that we'll probably depend on for very heavy computing applications. But we'll no doubt bolster an in-house computational infrastructure because there is always a need for local computing.

What compute infrastructure do you have on the ground right now?

There is not much because there hasn't been a coordinated biocomputing core that’s developed. Most of the compute infrastructure is handled by individual laboratories or is handled by the general IT group, but the IT group has not developed a biocomputing infrastructure, per se. There are programs and groups at the Danforth Center now that are using computing but many of them are using collaborators so the heavy duty computing gets done off site.

Again, the goal with this new round of hires is to bring in faculty who can bridge the biological and the computational and the quantitative and who can establish more of that expertise in-house. They will still collaborate externally but we are hoping that they will infuse a lot more computation and quantitative biology into the groups that are currently at the Danforth Center.

What are some specific informatics challenges?

Even though more and more effort has gone into development of genomic computational tools, we are still at a very primitive stage in our ability to understand what a genome sequence actually means.

Take, for example, a single genome. We are barely at the point where we can accurately predict all the genes. We are largely unable to understand the significance of the rest of the genome. We do not have good ways to analyze how the parts interact. What you would very much like to do is sequence a genome and then predict all of the interactions of the proteins and understand what their functions are, but we are so far away from being able to do that. The algorithms and predictive tools are just not available yet.

Furthermore, when you expand that to populations of plants, we would very much like to be able to sequence all genomes out there and that’s probably feasible. But then to understand what novel things plants can do, and then associate a genetic basis for those novel things — whether they be novel chemicals or the ability to grow on heavy metals or whatever the trait or set of traits are — we really need better algorithms. That becomes a computational, statistics, mathematics, and modeling set of problems.

There are a lot of immediate problems that have to do with how we handle and display and extract data. We don’t deal very well with the massive amounts of data that we already have in hand. For example, if you sequence 50 different variants of the genome of a particular species like Arabidopsis or soybean, how do you view that? Because all those variants are going to be different and there are going to be insertions and deletions, how do you visualize a cloud of genomes?

Speaking more generally now, what are some of challenges you see in the plant science space?

The big challenge is funding. There is no shortage of interesting and important problems to address, [but] the limitation is funding.

When you consider the whole landscape of biological funding in the US, biomedical science gets the lion's share of the biological research dollar. By contrast, plant science gets a fairly small sliver. The agencies that you might guess would be supportive of plant science like the USDA actually support relatively little in terms of fundamental plant science and even for applied problems, there is limited funding available for that.

There are organizations like the Bill and Melinda Gates Foundation that have supported individual projects and some of those are occurring at the Danforth Center. There is funding from the Department of Energy, [which] has ramped up [its] bioenergy research portfolio in the past couple of years, but by and large funding is the big challenge.

Do you think that perhaps there will be an uptick in funding as issues like biofuel and food production become more prominent?

Let's take those two things separately. We've seen an uptick in funds for development of new types of biofuels. Indeed renewable energy has been a big priority at DOE in this administration. For example, at Danforth, there is a very sizable set of grants that support new ways to produce oils from either plants or algae and the oils can go to replace things like industrial oils — diesel and so forth.

Now for agriculture and food production, I think the basic historical problem has been [that] once we figured out in the US how to produce food efficiently and food became very cheap as a percentage of family income, the interest in agricultural and plant science has been very low because it hasn’t been on anybody's radar.

We now have a situation where biofuels are in competition with the food supply. We have international agricultural problems that were never solved and that are becoming worse in some places. We have climate change and global environmental issues that pretty clearly indicate that water is a diminishing resource and high-quality land is limited.

We have this myriad of problems that I think we've, in the US, yet to see impact individuals in a meaningful way. However we are starting to see it. Food prices are starting to go up, [and] because we depend on oil for our fuel needs we have relatively high gasoline prices.

People are becoming more aware [of this, however,] and organizations like the Gates Foundation are very concerned about this and they are putting substantial resources into it.

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