Credit: Photo by Bob Skalkowski / Photography As a postdoc at the Whitehead Institute for Biomedical Research in Cambridge, MA, Mike Axtell would often come into the lab carrying bits of plants he had clipped from bushes by the sides of the busy roads. He would dump them on his desk and begin to prepare them for microRNA sequencing, hoping to determine wh" /> Credit: Photo by Bob Skalkowski / Photography As a postdoc at the Whitehead Institute for Biomedical Research in Cambridge, MA, Mike Axtell would often come into the lab carrying bits of plants he had clipped from bushes by the sides of the busy roads. He would dump them on his desk and begin to prepare them for microRNA sequencing, hoping to determine wh" />

Mike Axtell: The curious gardener

Credit: Photo by Bob Skalkowski / Photography" /> Credit: Photo by Bob Skalkowski / Photography As a postdoc at the Whitehead Institute for Biomedical Research in Cambridge, MA, Mike Axtell would often come into the lab carrying bits of plants he had clipped from bushes by the sides of the busy roads. He would dump them on his desk and begin to prepare them for microRNA sequencing, hoping to determine wh

By | April 1, 2009

<figcaption> Credit: Photo by Bob Skalkowski / Photography</figcaption>
Credit: Photo by Bob Skalkowski / Photography

As a postdoc at the Whitehead Institute for Biomedical Research in Cambridge, MA, Mike Axtell would often come into the lab carrying bits of plants he had clipped from bushes by the sides of the busy roads. He would dump them on his desk and begin to prepare them for microRNA sequencing, hoping to determine whether microRNAs were active throughout plant evolution. Most people would have ordered the plant samples from a catalog, says Graham Ruby, then a grad student in David Bartel's lab, where the two worked. "It was really amusing to see how far he was able to get with things people planted in an urban setting," says Ruby.

Axtell became interested in plants as an undergraduate at Ithaca College in New York. To him, plants simply seemed like a nonmessy way of studying genetics. "Plants are so easy to manipulate," says Axtell. For graduate work, he picked the lab of Brian Staskawicz at the University of California, Berkeley. As he was finishing his PhD in plant biology-immunology,1 Axtell started reading about microRNAs, which up until the year 2001 were thought to be biological oddities. By 2002, researchers had discovered them in plants. "I just got really excited by the fundamental questions that could be asked in this field," says Axtell.

Axtell applied for a postdoc position with Bartel, an animal microRNA researcher who was "eager to have someone come into the lab who knew how to work on plants," says Bartel. He quickly saw Axtell's potential. "He's the kind of person who's an early adapter," says Bartel, "or if the technique isn't there he'll invent it himself."

At the time, microRNAs were known to be important in flowering plants, but no one knew if they were present in other types of plants. Using a DNA microarray chip that he developed, Axtell found that mosses—which represent the base of plants' evolutionary ancestry—not only had many microRNAs in common with flowering plants, but also shared mRNA targets.2 These sequences are "unchanged in plant species separated by 500 million years of evolution," says Axtell. "It's like comparing C. elegans to humans."

Axtell wanted to find a faster way of studying the genetic targets of plant microRNAs. Normally in order to study a target, a researcher would try to match the microRNA sequence against a genome database of interest. The problem was that only the Arabidopsis genome had been fully sequenced at that time. Also, says Axtell, the match between sequenced microRNA and Arabidopsis database "is a prediction. It doesn't necessarily mean that microRNA actually forms a regulatory pair" experimentally, says Axtell.

So Axtell developed a way to scan the targets of plant microRNAs en masse, by scanning for the products of microRNA digestion: the chopped pieces of mRNA. Once cut, mRNA is unstable in the cell, and is quickly degraded. "I was not convinced that it would work," says then-grad student Ramya Rajagopalan, but Axtell "was really keen to try it out." He scanned for pieces of mRNA that contained a telltale sign of microRNA snipping: a cut at the tenth nucleotide in from where the microRNA binds to the mRNA. "We called it the degradome to be kind of cheeky," says Axtell.3 The comprehensive sampling of microRNA revealed that "we see not just a conservation of the microRNA but complete conservation of the target" across evolution, says Axtell, which contrasts sharply with the genetically drifting microRNA targets of animals.

In his own lab at Pennsylvania State University since 2006, Axtell is now working to characterize the types of plant mRNA that microRNA targets. "I think his future is very bright," says Bartel. "I think that he's taught me what it is to be a good scientist," says Rajagopalan. "He is this kind of guy that dreams stuff up—that's what a scientist needs to do."

Title: Assistant Professor of Biology, Pennsylvania State University.
Age: 32
Representative publications:
1. M.J. Axtell, B.J. Staskawicz, "Initiation of RPS2-specified disease resistance in Arabidopsis is coupled to the AvrRpt2-directed elimination of RIN4," Cell, 112:369-77, 2003. (Cited in 235 papers) 2. M.J. Axtell and D.P. Bartel, "Antiquity of microRNAs and their targets in land plants," Plant Cell, 17:1658-73, 2005. (Cited in 105 papers) 3. C. Addo-Quaye et al., "Endogenous siRNA and miRNA targets identified by sequencing of the Arabidopsis degradome," Curr Biol,18:758-62, 2008.

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