Free Range Problem-Solving

By Eric Sauter

These are interesting times for Peter Kuhn.

Most interesting to him right now is the successful test run of a new synchrotron, a particle accelerator that creates high intensity x-ray light. Until now, the dimensions of most synchrotrons could be described in terms of football fields—but this miniaturized machine will fit into a 3,000-square-foot laboratory.

The new synchrotron, a prototype produced by the Palo Alto-based Lyncean Technologies, was created by the marriage of two mature technologies, particle accelerator technology and solid-state laser technology. The advance will be a boon for structural biologists, who, using crystallographic techniques, are taking advantage of synchrotrons' powerful x-rays to study the structure of macromolecules and proteins.

"This is stellar," says Kuhn, an associate professor of cell biology at The Scripps Research Institute and life sciences director for the Scripps-Palo Alto Research Center Institute. "It's amazing. [President] Richard Lerner first proposed that Scripps Research should have its own synchrotron in the late '80's and now we have one that will fit into our laboratory."

That machine won't be installed until January of 2007 but that hardly matters to Kuhn. He is very much in the moment. "This is amazingly exciting for us, a major milestone. The first x-rays were generated by the prototype, it's working and functional, and our machine is being built. It will touch most laboratories at Scripps Research. This is very important for structural biologists."

A Scientific Conglomeration

In all this excitement, Kuhn probably would be hopping up and down except for the fact that he is still recovering from a serious knee injury that required surgery. True to form, he was flying over a cliff during a wilderness ski outing and tore the ligaments in his knee when he landed. Within 24 hours after the surgery was complete, he said, members of his research group showed up at his door to see when he was coming back. And he probably would have gone with them at that very moment had it not been for the fact that he was flat on his back.

"That I had to lie on the couch for seven days made it major surgery for me," he says. "It was a lesson in patience that for me was quite unique. But I'm now fully functional in the laboratory and I expect to be surfing on the Fourth of July."

Even aside from surfing, there are lots of projects that Kuhn has reason to be excited about these days. The synchrotron, a program of the Accelerated Technologies Center for Gene to 3D Structure, is only one aspect of the highly active scientific conglomeration that is the Kuhn-Stevens laboratories.

Kuhn's work on severe acute respiratory syndrome (SARS) proteins continues to move forward under the rubric of the Functional and Structural Proteomics of SARS-CoV Related Protein—part of a $15 million grant from the National Institute of Allergy and Infectious Diseases to study the pathogen, a project that includes multiple Scripps Research and Scripps-PARC faculty.

His laboratory is also involved in a $15 million National Institutes of Health Roadmap study on innovative membrane protein technologies. Led by Scripps Research Professor Raymond Stevens, the goal of the study is to develop reliable and cost-effective technologies to produce integral membrane proteins for research. Kuhn also leads the Scripps Novartis protein-protein interaction project, now in its third year investigating the modulation of protein interactions for therapeutic intervention.

Then there is the work of the Cancer Bioengineering Research Partnership, which has developed an instrument capable of rapid and accurate detection of rare cancer cells in circulation using fiber-optic array scanning technology (FAST), one that works 500 times faster than conventional automated digital microscopy, according to a new study just published in Biosensors & Bioelectronics. The technology, as the study points out, "has the potential to serve as a clinically useful point-of-care diagnostic and a prognostic tool for cancer clinicians."

The Art of Translation

This is more or less the theme of his laboratory—to go from basic science to the patient with everybody working together. When you ask Kuhn about the nature of these various projects, however, the word he chooses is translation. Indeed, so much of what he does involves just that—translating biology to the engineers at Scripps-PARC and translating research to clinicians, for example. Kuhn may be the original free range scientist, roaming through various disciplines at will, a technological version of the original Baedeker's guide stuck in his back pocket to help get him through the rough terrain.

"Coming from Germany with a degree in physics as I did," he says, "I was trained in a solution-finding approach to things without restriction of topics or discipline. This is what we find fun to do—and when you get thrown into a new language environment, you have no choice. You learn the art of translation from scratch and you learn it as fast as possible."

The language part was never hard for Kuhn, because he'd lived around English speakers, American or otherwise, for a long time. This also gave him a good grasp of American and European cultures, which are so similar and yet so different—the same kind of similarities and differences he found whenever he crossed scientific disciplines. The language is still easy for him and it shows. Kuhn often speaks in entire paragraphs, great enthusiastic gulps of words that sometimes emerge so complete that it seems he's reading them off a teleprompter running in his own head.

"After studying physics in Germany, I moved into molecular biology in the United States," Kuhn says. He received his master's degree in 1993 and his Ph.D. two years later from the State University of New York, Albany. "Some of the learning process was in the discipline of understanding the actual language that you're using. When you go through this translation process so many times, it becomes part of you. That's what's attracted me to Scripps and the PARC research project—it was and is an enormous translation challenge. Our task is to create a bridge from innovative physics to innovative cell biology and biophysics, and then all the way to the pathology and clinical oncology of the Scripps Clinic."

Kuhn arrived at Scripps Research from Stanford in 2002 to help steer the enormously complex collaboration between two enormously complex research institutions, each with its own language and culture. The FAST cancer cell screening was one of the first products of that merger, but there have been others, including the development of new software to accelerate mass spectrometry of proteins and a new system to directly measure molecular interaction that will eliminate the need for custom assays as well as reducing costs.

One Plus One Equals Ten

Although the target of nearly all of Kuhn's research has been proteins, understanding their structure and deciphering their interactions, the goal of his work is much larger.

 "What excites me is having an impact on human health," he says. "What excites me professionally is problem solving. And what pushes me personally are a few key events—most importantly, my mother surviving breast cancer due to early-stage radiation. I know that by bringing research and the clinic together as early as possible it can result in survival—that's a powerful message to me personally. As Ray Stevens said to me, 'We can drive our research all the way to the patient and we must never lose sight of that.'"

Kuhn runs his own laboratories along what he calls non-hierarchical lines, something that to him seems completely natural in a place like Scripps Research and more than worth the effort.

"Here is a place crowded with people who have tremendous competencies and intellects," says Kuhn. "If we work in a collaborative way, the common gain should be enormous. The synchrotron is a perfect example. If we put this new machine—which is an instrument of physics—in a physics lab, so what? If we plunk it down in front of [Scripps Research investigators] Ray Stevens, Ian Wilson, Jack Johnson, or Jeffery Chang, all of a sudden there's an explosion of scientific creativity because these scientists will exploit its potential. Everything we do is a natural collaboration that makes perfect sense. "

As a result, Kuhn says, he drives into work fired up everyday.

"We have put in place a research framework, have proven that it works, and are now putting these pieces together," he says. "That's why enabling instruments like the synchrotron or the FAST scanner are so important. Once you put together the right scientists and the right clinicians and the right programs, you add some very creative graduate and postdoctoral fellows, and you set it up so everyone talks to one another, then suddenly one plus one becomes ten. They are able to do things not achievable before."

Send comments to: mikaono[at]scripps.edu

Associate Professor Peter Kuhn is excited about a successful test run of a new miniaturized synchrotron, a particle accelerator that creates high intensity x-ray light.

The new machine will be a boon for structural biologists, who use the powerful x-rays from synchrotrons to study the structure of macromolecules and proteins. Click to enlarge