I N T E R N A T I O N A L P A G E 15
UK 32 - 6 MEI 2010
Addicted to enzymes |_
Poelarends gets his kicks finding out how they work
| i n t e r v i e w | He’s making natural enzymes do unnatural things. That way, he hopes to help the chemical industry become cleaner and more efficient. But his ultimate drive is to understand how his enzymes work. By René FRansen The news came when he wasn’t expecting it anymore: an EUR 2 million ‘starting grant’ from the European Research Council (ERC). “It was on 8 February, and it came as a bit of a shock. I had even already filed an application for the 2010 ERC starting grant round.” Biochemist Gerrit Jan Poelarends had known since last summer that he was in with a chance. “My application for the 2009 round went well. I was invited to Brussels for an interview and the committee seemed very interested. But I ended up on the reserve list and would only get a grant if there was enough money.” Europe being what it is, this meant that Poelarends had to wait and see if all the participants in the ERC would honour their pledges. “It’s only at the end of the year that the ERC knows its final budget. And in the end, my application succeeded.” So there was cake for the department, as well as lots of negotiations and paperwork. “When you get a grant from the Dutch research organization NWO you have to fill out a one-page form. For the ERC, it’s a whole stack. And you have to negotiate the terms of the contract.” But after all that work, he has a budget of EUR 2 million. “I’ve got five PhD students at the moment, and that will double.” The grant also secures his tenure-track appointment, “but the application for tenure will have to wait. First, I have to assist some of my students with a couple of important papers. They need them for their theses.”
Passion It’s not the money that drives him – even though he admits that he almost took a degree in econometrics. “It was either that or biology. Then I heard a wonderful talk by a behavioural ecologist and was totally seduced. So I chose biology, in Haren. But then I took a course in molecular biology. Animal behaviour studies seemed so descriptive whereas molecular biology and biochemistry really taught you something about the mechanism of what was happening. And that is really where my passion lies, finding out how things work.” He’s now applying his passion to enzymes, the proteins that catalyze so many chemical reactions in our bodies – or in any other biological system. The chemical industry is interested in enzymes because they work fast and are clean – no noxious solvents needed, just add water. The way new enzymes are discovered is by looking for them in nature. “You search for enzymes
Photo Jeroen van Kooten
Gerrit Jan Poelarends with some natural capacity to catalyze the reaction you want, and then tweak the enzyme to make it work better”, Poelarends explains. “But we’ve taken a different approach.” He’s looking more deeply into the chemistry of things. “There’s a field called organo-catalysis which studies how organic molecules catalyze chemical reactions. This taught us that one particular reaction we were interested in, the creation of a new bond between two carbon atoms, was catalyzed by the amino acid proline.”
‘I get a real kick out of that’ So Poelarends began to look for an enzyme that had a proline in its active site (that’s what you call the part of the enzyme where the chemical reaction takes place). “And the
proline also had to be at the start of the peptide chain that forms the enzyme”, Poelarends explains. There appeared to be a family of enzymes that fitted the bill called tautomerases. “These enzymes are not known for creating these chemical bonds between carbons. They do something entirely different. But when we tested some, we found they could indeed catalyze the reaction we wanted.” This way, he hopes to end up with an enzyme that can efficiently catalyze a crucial reaction in the production of the cholesterol-lowering drug Lipitor. However, finding commercially interesting enzymes is not Poelarends’ aim. He wants to know how these enzymes work. The chemistry is complicated, but he finds this very stimulating. He sketches some chemical structures on a whiteboard to explain what is happening. Electrons jumping from one atom to the next, getting caught and forming bonds with another molecule... He’s showing what happens ‘under the hood’ of these en-
Structure of a tautomerase enzyme zymes, something that is not common practice in the enzymology world. “You know, there’s an enzyme called aspartase which has been studied for almost 100 years. But nobody knew how it worked. We’ve recently figured that out, together with the structural biology group here at the University. I get a real kick out of that.”
success What remains to be explained is
how Gerrit Jan Poelarends became so successful. Apart from his ERC grant, he previously landed not only a Veni but also a Vidi grant from NWO. “To be successful, you need drive”, he explains. “You have to really want to climb that academic ladder and invest a lot of time in building up your CV. Then the time to harvest will come.” His family (wife, three children) sometimes complains when deadlines make him work overtime. “I live in Ommen, an hour’s drive from Groningen. In that hour, I try to switch from researcher to husband and father. And the weekend is for my family.” Unless, of course, he has to sneak an extra hour on Sunday mornings to finish an important paper. And yes, his urge to explain the mechanisms is at times too much for his family. “When we walk through a forest on Sunday mornings, my wife sometimes tells me to stop explaining. ‘Shut up dear, I don’t think the children are really interested’, she says.”