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Trawling for Meaning Beyond Sequence

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  • Title: Postdoctoral Researcher, European Molecular Biology Laboratory, Heidelberg
  • Education: PhD, University of Cambridge, 2004
  • Recommended by: Ewan Birney

If there’s one thing Laurence Ettwiller has learned from her time in the genomics field, it’s the importance of collaborating with people from a range of different backgrounds. That’s not to say that Ettwiller herself can be easily pigeonholed, though. A biologist by training, she came to see the need for a better understanding of the computational side of things after she completed a master’s degree in cellular and molecular biology and worked for a few years as a technician for New England Biolabs and Millennium Pharmaceuticals. “I realized I was really interested in doing analysis of the data,” she says, so she went back to school and earned her PhD in pure bioinformatics.

Today, Ettwiller is a postdoc at EMBL in Heidelberg, where her advisor is Jochen Wittbrodt. She makes sure that her projects involve an experimental aspect as well as computational work. Her particular interest is in “gene regulation at the transcriptional level,” she says, and part of her research includes making predictions and then validating them in the model fish Medaka.

Ettwiller, who developed an algorithm to map regulatory sequences and protein functions in yeast to help determine functional regulatory motifs, has recently been a collaborator on a project that searches for overrepresented motifs, predicts whether those motifs will exist in other species, and aims to define the binding site for a transcription factor of interest. The resource, known as Trawler, relies on chromatin immuno-precipitation data and is publicly available. Other partners on the project include Ben Paten, now in David Haussler’s lab at the University of California, Santa Cruz, and Mirana Ramialison, another scientist with EMBL.

That collaboration is just one of several Ettwiller is currently participating in. “I find this is very important — to be able to do many different things with many different people, and somehow having a different mindset and approaching the question from many different angles,” she says.

Among the themes of Ettwiller’s work is the idea that “inside the [genome] sequence is valuable information that we don’t really understand,” she says. For example, she adds, “we know how to analyze activation of a gene, but it’s a bit harder to analyze repression of a gene.” Regulatory elements, for instance, have proven especially difficult: “They’re very short, they have low information content, their code is really hard to decipher,” Ettwiller says — but their importance is indisputable. So she hopes that her work, as well as other scientists’ efforts, will help the community trace and understand elements like these.

Looking ahead

In the coming years, Ettwiller believes that scientists will be faced with the dilemma of finding experimental approaches to validate the many predictions that can currently be made but are much harder to test in a biological system. “We need to find experiments that answer the questions that we are asking,” she says. She also thinks that working in highly interdisciplinary teams will be a boon to the field — even disciplines as far flung as astronomy or information theory could offer a lot to genomic scientists, she says.

Publications of note

The Trawler project with Paten and Ramialison is a good example of the kind of work Ettwiller enjoys, and a paper describing it came out this summer in Nature Methods. (“Trawler: de novo regulatory motif discovery pipeline for chromatin immunoprecipitation.”) With senior authors Ewan Birney and Jochen Wittbrodt, the team describes the tool, its effectiveness in calling binding sites from ChIP data from yeast and mammals, and its Web interface. The standalone tool is still in development, but you can access the Trawler pipeline through EMBL’s website at ani.embl.de/trawler.

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