From Theoretical Physics to Understanding Disease: Shifting Focus Proves Successful for Luijten

Side view and cross-sections of a bundle of F-actin filaments (blue) held together by lysozyme (orange), as predicted by molecular dynamics simulations.
Side view and cross-sections of a bundle of F-actin filaments (blue) held together by lysozyme (orange), as predicted by molecular dynamics simulations.

Erik Luijten's academic training was in theoretical physics but he wasn't afraid to take his research interests in new directions, one of which may lead to better treatments for cystic fibrosis patients.

Theoretical physicists don't usually earn thank-yous from the parents of children with cystic fibrosis. But then Erik Luijten isn't your typical theoretical physicist.

Luijten and collaborator Gerard Wong are Beckman Institute researchers whose 2007 paper provided new insights into fighting bacterial infections in cystic fibrosis patients. In a Proceedings of the National Academy of Sciences (PNAS) paper, the pair demonstrated through a combination of experiments and computer simulations why long-term bacterial infections, a leading cause of death for those afflicted with cystic fibrosis, were able to resist current treatments while also describing a model for the possible future development of antimicrobials that would fight long-term infection.

"Coming here has stimulated me in so many ways - it completely changed my research focus. It is unrelated to anything that I did before." - Erik Luijten

Luijten, a member of Beckman's Computational Multiscale Nanosystems group and Associate Professor in the Department of Materials Science and Engineering and the Department of Physics, said that after news of their work was made public, he heard from parents of cystic fibrosis patients from across the country.

"It was interesting because when we do other, what I would call exciting projects, the feedback is limited or subdued," Luijten said. "Here I received e-mails after the press release came out from parents sending me pictures of their children, saying 'my child has cystic fibrosis and this (discovery) is so fantastic,' which of course never happens normally. They wrote 'if you're ever in my state stop by,' that sort of thing. In that sense it felt really good."

Luijten's contribution to the project was his expertise in the area of computer simulations of soft materials, specifically complex fluids. As he did in the cystic fibrosis project, Luijten takes the work of experimental researchers like Wong and adds the element of dynamic computer simulation in order to gain a better understanding of the workings of complex fluids. It was an area he was hardly familiar with before coming to the University of Illinois.

"When I came here seven years ago there were several people who were doing really exciting experimental research in this area," Luijten said. "So I was very intrigued by the results that they described and I thought, hey, with the sort of simulation techniques which I have mastered and used for a lot of different problems, I could also try to understand these types of systems."

So Luijten created a new research path for himself, based upon his knowledge of computer simulations and his excitement over the work of experimentalist researchers like Wong, and fellow Beckman colleagues Paul Braun, Jennifer Lewis, and Steve Granick.

"I try to find clever ways of using computer simulations to understand the systems that the experimentalists study," Luijten said. "Really, the second that I came here I got so much exposure to exciting topics and to colleagues who were excited about what they are doing.

"Coming here has stimulated me in so many ways - it completely changed my research focus. It is unrelated to anything that I did before. I am a person who likes change a lot; I always like to be stimulated. I don't like to make things easy for myself."

Luijten certainly didn't make things easier on himself by shifting his research focus or by taking a road-less-travelled approach.

"I was not truly aware of this type of research (on complex fluids) and I jumped into it not realizing how complicated the simulations would become," he said. "We try to understand from a mechanistic point of view what is going on in these systems, how can we explain the experimental results that are reported, given the ingredients or the components of these systems."

In order to do that, Luijten had to break some new ground in applying his computational methodologies to biological processes.

"In going this whole other direction with my research I realized that many of the existing simulation methods were just not adequate for studying these sorts of systems (complex fluids)," he said. "The ideas are correct but the systems are so complicated that it would take forever. So I always try to be smart about how to address a particular system or problem that I encounter. We developed several new simulation techniques that have turned out to be extremely powerful."

Luijten's approach is to create computer simulations that have the same components an experimentalist finds in a lab experiment. The goals, as his research summary states, are to "first, understand experimentally observed phenomena from the underlying microscopic features of a system, and second, to test the predictive value of analytic theories describing these systems. The insight thus gained allows the prediction of yet unknown properties of materials and the design of new materials."

To accomplish these goals, Luijten uses a few standard computer programs but most are new simulation methods developed by his own group. A few years ago, he reported on a breakthrough geometric cluster algorithm for use in Monte Carlo simulations.

"It was spectacularly efficient compared to anything else that existed and it has made its way into textbooks already, which is amazing," Luijten said.

In the project with Wong, Luijten's molecular dynamics simulations were able to gain insight into the thick mucus that forms inside a cystic fibrosis patient's pulmonary passages and that serves as a breeding ground for bacterial infection. Luijten's computational model predicted this process and aligned with results from X-ray scattering experiments.

"It would be more precise to say that we came up with the proper methodology to study this system to understand what's going on," he said. "Modeling can be simple and straightforward, but then how do you investigate this model, what are the things you have to study about it to answer what is going on in the experiment?"

While he appreciated hearing from parents of cystic fibrosis patients, Luijten said he knows any possible treatments are well into the future.

"This is not a medicine we created," he said. "It's some insight into what might be going on. I'm fairly convinced that that picture is true, but it's not the cause of cystic fibrosis. The cause is a genetic defect which we are not curing. But we understand that as a result of that defect certain symptoms happen and we understand why some of the current techniques that are used to fight those symptoms are not working. Given that insight, this is one way you could change the fight against the symptoms. But it would be a long road."

Even without feedback from the public, Luijten finds his research exciting.

"Once you get involved in it, there are so many things that are still unknown about the systems, whenever you look at them you encounter so many surprises," he said.

"It's only in the last 10 years or so that computers have become powerful enough to reasonably study these, which by itself is kind of interesting because if it hasn't been done in the last 10 years I don't have to worry that anybody has sorted it out already," he added with a laugh.

Luijten said his collaborations with materials science researchers mean his work is an interdisciplinary enterprise.

"The fact that the people I work with are all in materials science might hide the fact that it is actually interdisciplinary," he said. "I come from my side doing computer simulations and my training is in theoretical physics, so I often transfer ideas that I know from completely different areas of computational physics into this area of soft materials or complex fluids.

"I then try to combine it with these people working with a range of experimental techniques. In my view that's completely interdisciplinary, but in my view the whole department is interdisciplinary. You can see that in the affiliations of these people, all of them have affiliations in other departments as well: physics, chemical engineering, chemistry. It's no surprise that many of these people are at the Beckman Institute too."

Luijten came to Illinois in 2001 and joined Beckman in 2006 as a natural progression of his expanding research interests.

"I felt there was a lot of exciting stuff going on at Beckman and I'm always looking for challenges," he said. "I really got excited by the types of experimental results here. For me it is an important driving force, all these exciting topics that are so different from what I've seen before."