An abattoir saves the day
When Timm Maier arrived at Nenad Ban's lab at ETH Zurich in early 2004, he was looking for a project that would push him to his limits. Not long before, ETH's Simon Jenni had obtained well-diffracting crystals of fungal fatty acid synthase, so Maier decided to go after its mammalian analogue.
"It was a funny project," says the German-born protein crystallographer, who completed his PhD at the Free University in Berlin. Since the 1970s, other groups had repeatedly shown that "it was impossible to obtain diffraction-quality crystals," he says.
But Maier needed to jump over another hurdle before he could even start trying to grow crystals: He needed a good source of...
After pondering the problem for a while, Maier remembered that fatty acid synthase is overexpressed in lactating mammary glands. With nothing to lose, he put in a call to the local abattoir, or slaughterhouse, to see if they'd sell some to him.
"Before that moment, I hadn't thought of going to the slaughterhouse, but they said it was no problem. In fact, they had a price list. It was 15 Swiss francs per organ." (At those prices, Maier says, he had to resist the temptation to order a bunch of steaks in the name of medical research.)
Over the coming months, trips to the abattoir became a regular event, as Maier needed about 150 grams of tissue every few weeks. After isolating and purifying the protein, he tried growing crystals under thousands of different conditions. "For each of the proteins I purified, I screened about 3,000 conditions," he says.
For that process, Maier used the robotic crystallization facilities of the Swiss National Center of Excellence (NCCR) in Structural Biology, established on campus at ETH a few years ago as a collaboration between ETH and the University of Zurich. The system images each droplet automatically, but also allows researchers to review them manually on their desktop computers.
After about nine months, Maier spotted tiny 3-µm crystals in a single well, which the computer had missed. "Out of 10,000 drops there was one that had crystals," he remembers. "I just smiled for five minutes and went to ask three or four colleagues if they thought they were definitely crystals."
They were, and three months later, Maier had generated diffraction patterns at the synchrotron. "When I started this project I estimated my chances of getting crystals was 20% to 30%. I would have given it exactly two and a half years to get some indication before I gave up." Instead, he ended up being the first author on a paper that appeared on the cover of Science in 2006 (311:1258-62), two years after arriving at ETH. "It's mostly based on luck," he says.