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Q&A: JCVI's New Rockville Campus Director Karen Nelson on Current and Future Sequencing Projects


karennelson.jpgName: Karen Nelson
Age: 45
Position: Director of the J. Craig Venter Institute Rockville campus, since 2009
Experience and Education:
Other positions, JCVI, since 1996
PhD in microbiology, Cornell University, 1996
MS in animal science, University of Florida, Gainesville, 1992
BS in animal science, University of the West Indies, Trinidad and Tobago, 1987

Karen Nelson was recently named head of the J. Craig Venter Institute's Rockville, Md., campus. She succeeds Robert Strausberg, who is moving to the Ludwig Institute for Cancer Research as director for collaborative sciences.

Nelson has been with JCVI since 1996, when she came on board as a postdoctoral fellow and the center was still known as the Institute for Genomic Research. She was involved with the institute's early metagenomic projects, including its first metagenomic analysis, published in 2006, of the microbial diversity found in human fecal matter.

Nelson also led the team that sequenced the bacterium Thermotoga maritime, which lives in 175 ºF water. She eventually became the director of human microbiology and metagenomics in the department of human medicine and genomics at JCVI and has played a large role in the human microbiome project, which aims to characterize and analyze the entire human microbiota.

Recently, Nelson spoke with In Sequence about the future of JCVI's research and how new sequencing technologies are expanding the scope of what researchers there are able to study.

What are your plans and what projects are you involved in as the new head of JCVI's Rockville campus?

My training is as a microbiologist, so I'm very excited about looking at the areas of metagenomics, and looking at all the microbial species that we have not been able to culture but now we can access with these new sequencing technologies.

We have a very strong infrastructure in terms of sequencing and data analysis. We have a very strong informatics team involved in the annotation and comparative analysis of these large data sets. So I expect that we will continue to play a major role in terms of the metagenomic analyses of not only the human body but a number of other environments.

We have collaborations looking at the metagenomics of domesticated and wild animals, and we have a huge pipeline analysis of viruses, particularly flu, that's funded by the NIAID. We're looking at viruses in the environment and how viruses hop from their natural reservoir into humans.

On the environmental side, we were approached by the University of the West Indies to go to Trinidad and start sampling some of the areas where they have oil reservoirs, to use microbial-based approaches and metagenomic-based approaches to help look at the methane cycle in cleaning up the environment.

So, we have a number of very large-scale studies — both single genomes and large metagenomic studies — that I expect will continue to expand and diversify.

Will you be going in any new directions in the coming years?

I'm hoping to take advantage of the new sequencing technologies, and the whole area that is allowing us to generate larger data sets. We have the tools to analyze the data, but now we can actually generate the data at a reduced cost and in much larger quantities than you could imagine before.

Going beyond gene sequencing, I'm also looking at the transcriptome and the whole area of meta-transcriptomics.

And also, partnering more closely with the traditional microbiologists. The thing that is obviously coming out of sequencing now is that we really can't culture a lot of these organisms, but we can probably figure out ways to pull them out of the environment, for example, using single-cell approaches. We can now start to figure out how to pull out single cells and get the genome of something that hasn't been cultivated before and, using a reverse of the traditional approach, figure out how to culture these isolates now. So I think that whole area of using sequencing to pull out uncultured isolates and figure out their physiology and what they're really about is going to be really exciting. We have a group here that is focused on looking at single-cell isolates — pulling these isolates out, generating their genome, and then hopefully culturing some of these guys.

What sequencing technologies are you using?

We work very closely with the companies that produce the instruments and we're continuously exploring new avenues and keeping ahead of the newest technologies that are out there. We're working with Illumina, [Roche's] 454 [group], Life Technologies. We are also looking at Pacific Biosciences.

We have 454 on campus, and we also have both [Illumina] and SOLiD systems. So we're working on all different platforms. And also we're looking into when you merge the datasets and samples and different platforms together — the different platforms have different benefits. Some are longer, some are shorter, some give you much more data than others. We're constantly looking into exploring those.

[In the human microbiome project], we're using a combination of all platforms. We're even doing a little bit of Sanger. We're doing a lot of 454 and [Illumina] and we'll be working towards assembling large data sets based on both platforms. The different platforms have different benefits and we're aiming to take advantage of those. Just as an example, some of the isolates for our reference genome sequencing are closely related. So, you can [sequence one of the isolates] with 454, and then you can do multiple, closely related cousins on different platforms, and you get deeper coverage at reduced cost. We are being very creative in terms of how we merge different platforms of sequencing — it's not going to be one single platform.

Where are you in the human microbiome project, and what will you be doing going forward?

We have multiple projects. One component is devoted to the four large-scale centers – Baylor [University], JCVI, [the Broad Institute], [Washington University] — and for that part we are sequencing from 15 to18 different body sites. I think it's close to 600 people now that we have recruited. So, different samples from the body sites are being sent to the centers and they're all being collated and then hosted by the data analysis and collation center. So we are creating primarily a huge resource for the community.

In addition to that, we are going to be doing between 200 [and] 300 reference genomes with the hope that we will be able to align a lot of this metagenomic data to these reference genomes. The [human microbiome] consortium is doing between 900 [and] 1,000 reference genomes, but just at JCVI, we're doing 200 to 300. And, for that we get samples from all over the world.

In addition, we were awarded two demonstration projects. So, I have a project at [New York University] with Zhiheng Pei, where we're following 80 individuals over the next few years and looking at esophageal cancer. We have preliminary information that would suggest that there is a microbial component to cancer of the esophagus. And, another individual at JCVI who works very heavily on the human microbial initiative is Dr. Barbara Methe. She also has a demonstration project from the National Institutes of Health looking at psoriasis in collaboration with Dr. Martin Blaser [at NYU].

You mentioned earlier being excited about taking advantage of the new sequencing technologies. How are these advancements in sequencing technology impacting the scope of what you're able to do, and the pace of your research?

The scope became much larger. I always tease my colleagues and say that in 2006 you could get on the cover of Nature with two people. And now, it's like, if you have a hundred, well maybe that gets you in one of the top journals. So things have really changed in the past few years.

I think by virtue of having access to the new technologies, we can adapt questions beyond just our immediate area. For example, we would like to be able to look at diseases in the developing world. And now we can probably do that because costs have come down so much. You can focus on a population beyond just the populations that have been most traditionally studied. So I think it's really expanding the concept of which diseases we can look at, which health conditions we can look at, and even for the environment, we can now sequence much deeper in the environment, and access microbial diversity far beyond what we could have done five or ten years ago.

But in parallel with that, we've had to obviously keep up the pace on the data analysis side and data storage side because you have so much more data coming out. So that's also been another exciting area for us. We have people like Shibu Yooseph and Granger Sutton. They work very closely with the data and look at the assembly approaches we have to use and the metagenomics tools that have to be adapted.

One of the things to point out is that of the large sequencing centers, JCVI has been at the forefront of metagenomics and has probably processed the largest number of metagenomic data sets just by virtue of when we got on board in the process. So, we've really had to keep apace and learn rapidly the new tools — what works, what doesn't work, and how we have to grow to adapt to new sequencing technologies as they come on board

It's actually never been dull, but especially in the last few years with the new sequencing technologies, it's become particularly exciting.

And I think also, we can now ask this question about the rare species in environments. I think because we were limited before by sequencing depth, we were not able to drill down and see what they call the minor players. And now we can actually start to access these organisms. Just to give you an example, Scott Peterson, who is at the [JCVI] Rockville campus, has been looking at oral plaque and he has been able to show you using subtractive hybridization approaches, that when you pull out the dominant players you can see up to 50 to100 species that you have not seen traditionally before as being present in the oral cavity. And that's because people have not been able to drill down to that depth previously.

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