Assistant Professor, University of Toronto
Recommended by Susan Lindquist, Whitehead Institute
NEW YORK (GenomeWeb) – When Mikko Taipale joined Susan Lindquist's lab as a postdoc, he was interested in the evolutionary work going on there. He started on a project examining whether prions like the ones that cause like Creutzfeldt-Jakob in humans could have more positive, useful roles in other organisms.
After a few years, though, that project didn't seem to be going anywhere, and Taipale switched gears. He instead began to work on how chaperones could buffer genetic variation by binding mutated proteins to stabilize them.
He then set off to develop a genome-wide assay to look at chaperone interactions quantitatively.
"It eventually worked really well and it provided a lot of opportunities and approaches — opportunities to expand it to start doing even higher throughput than I ever imagined," Taipale told GenomeWeb.
In his own lab at the University of Toronto, Taipale is continuing to study the chaperone system, but he's also interested in developing new technologies. He argued that many of the recent biological discoveries have actually been technological advances. RNA interference, induced pluripotent stem cells, and CRISPR, he said, are all technologies that are driving new research — RNAi enables knockdown studies, iPS cells help with modeling disease, and CRISPR allows for genome engineering.
"If you come up with a new technology, then it opens up a lot of avenues," Taipale said. "So, in that sense, I'm interested in developing new technologies to look at mostly protein-protein and drug-target interactions and biomolecular interactions."
In particular, he's interested in studying interactions that aren't always amenable to current technologies, such as ligand-receptor interactions and E3 ligase-target interactions.
Paper of note
In Nature Biotechnology last year, Taipale and his colleagues reported that chaperones could be used as thermodynamic sensors to study drug-target interactions.
They'd noticed that the interaction between HSP90 and its target kinases was sensitive to the conformation of the kinases, and when a small molecule binds the kinase and stabilizes it, the chaperone was then less likely to bind the kinase. This, they figured, could be used as a signal to indicate whether small molecules were binding kinases in vivo. Using this assay, they found that crizotinib targets ETV6-NTRK3 and inhibits the proliferation of ETV6-NTRK3-dependent tumor cells.
"It was completely serendipitous, I never planned anything like that," Taipale said. "It was an experiment in the lab that was, 'oh that's kind of interesting, I wonder if I could follow up on this?' And then it turned out that it worked really well."
The field is in "a really nice moment now," Taipale said. Relatively new techniques like CRISPR and iPS cells are enabling new types of studies and "we don't even know what we can do right now," he said.
It's hard to say, he added, what new technologies will be coming along in the next few years to change how people think and go about addressing their research questions.
"Technological discoveries just change the way people think and suddenly they work on something completely different," he said.
And the Nobel goes to…
Taipale said that if he won the Nobel Prize, he'd turn it down like Jean-Paul Sartre did. He said that prizes do more harm than good to the scientific enterprise. The difference, he added, between the people who take home the prize and those who just missed out is negligible.
"It just makes us forget that we're all trying to discover new things, something about nature and how the world works," he said.
This is the fourteenth in a series of Young Investigator Profiles for 2015 appearing on GenomeWeb.