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Duke Research - Welcome to the 'Intellectual Hotel'

Nicholas Katsanis

Nicholas Katsanis uses zebrafish as models of human disease, combing through huge libraries of disease genes to find hidden patterns. (Duke Photo: Jared Lazarus)

February 1, 2011

Welcome to the 'Intellectual Hotel'

Many Minds May Make Light Work

By Ione Echeverria and Marla Broadfoot

(A longer version of this story originally appeared in DukeMedicine Magazine )

Nico Katsanis, PhD, says the new model of doing science should be to abandon the model.

“A lot of the problems we are now facing are experimentally intractable through a single approach,” he says. At the same time, research is becoming so specialized that the journals of one researcher’s discipline read almost like gibberish to a researcher in another field.

What’s needed now, Katsanis believes, is the dissolution of the classical boundaries between departments -- and a means to help them learn from each other.

The Center for Human Disease Modeling, which he launched at Duke in December 2009, is the result of this vision: what Katsanis calls “an intellectual hotel” where investigators from diverse scientific and medical disciplines can meet and collaborate to challenge and perpetuate each other’s science.

The center offers Duke researchers a place to bring their new, perhaps unusual ideas and find peers who can analyze them, critique them, and figure ways in which their own research might catalyze discovery in the work of others. Pivoting around the central idea of using broad basic science to assist the management of patients, the center is investing heavily in the development of tools that can be used to solve problems of clinical significance. For example, the center has worked with a number of investigators to help develop functional assays using small animal models such as worms or zebrafish  to understand how genetic variation can contribute to human disease.

“The idea is to provide a little bit of activation energy,” says Katsanis, “and support for the early stages of synthetic work—specifically for projects that may otherwise not be funded by traditional routes, because they are either too high-risk or too premature.”

 

brachydanio rerioZebrafish share 70 percent of our genes and can be 'humanized' for research.

Since zebrafish share 70 percent of their genes with humans, they can also be “humanized,” meaning that the fish version of a gene or set of genes can be replaced by their human equivalents. Such model fish – which also have handily transparent embryos – are being used by the center to study muscular dystrophy, blood vessel formation, and a rare condition Katsanis studies called Bardet-Biedl syndrome (BBS), a genetic disorder affecting the hair-like cilia on the surface of many cells.

 

The only requirement for researchers to participate in the center is that their work must have, even if only very loosely, some link to human health. Katsanis is excited about the opportunities he sees for seemingly unaffiliated science to connect in this way—to get clinicians and researchers talking, when otherwise they might not.

For example, Katsanis is currently collaborating with Ronald Goldberg, MD, chief of neonatology, and colleagues on a new hybrid taskforce in which pediatrics research scientists and clinicians can get together and look at particularly vexing cases. “Duke University Hospital is a major referral hospital, which means that we see patients with challenging diagnoses and murky outcomes,” he says. “In some instances we can make the joint decision to bring these cases into the lab and see what we can develop from it. My thought is that these efforts will not only inform the care of the patient, but also sprout out to experimental avenues that we have never even thought about.

When he first tackled BBS as a postdoctoral researcher, Katsanis took an unusual tactic: he analyzed every single disease variant reported in the genes of BBS patients—about 150 in all—and examined their function in zebrafish. The results have been surprising. In 20 percent of BBS patients, it takes a combination of three mutations to manifest the disease.

“We have a far more precise—not fully accurate— but far more precise notion of the disease architecture from doing this experiment,” says Katsanis. “And I am willing to bet—in fact, I am betting my entire career—that this is going to be an approach that will be useful for many other problems of clinical relevance.”

Teamwork is also essential. “When I was conducting research into Bardet-Biedl syndrome, I felt the need to be a nephrologist, ophthalmologist, psychiatrist, pulmonary biologist, the list goes on. I couldn’t possibly do all those things and do them well,” Katsanis adds. “That is the point where I started to branch out and seek out colleagues to help me. Many people have helped me during the course of my career, and now it’s time for me to use that model and pay it forward.”

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