By Tiffany Fox, (858) 246-0353, email@example.com
San Diego, Calif., Aug. 25, 2010 —Biomedical researchers from around the world spent a week at the University of California, San Diego, as part of the fifth annual National Biomedical Computation Resource (NBCR) Summer Institute, an opportunity for hands-on training with a wide variety of cutting-edge tools that enable multiscale biomedical modeling and visualization.
Biomedical computation – which applies statistics and computer science to the field of biomedical sciences – is often a cheaper alternative to traditional experimental approaches and can speed the rate at which drugs are discovered for a host of human diseases.
The annual NBCR Summer Institute, which took place from Aug. 2-6, provided an overview of the challenges pertaining to cyberinfrastructure and multi-scale modeling approaches and offered opportunities for networking among researchers and participants.
Explained NBCR Principal Investigator Peter Arzberger: “Our principal activities at this year’s Institute focused on engaging participants in using technologies developed to address three areas of translational research: Individual patient modeling, especially with cardiac disease; subcellular modeling; and molecular modeling for the drug discovery pipeline.
“We also focused more this year on our resource and trying to build a future user base,” added Wilfred Li, executive director of NBCR. “And we did that by making a real attempt on our part to really be as open and available and interactive with students as possible.”
For the first time, certain researchers who presented posters at the Summer Institute were asked to give talks to the larger group about their findings. UC San Diego post-doctorate researcher Johan Hake of the Department of Bioengineering presented his research about the calcium dynamics in normal vs. failing heart cells during heart attacks.
“Calcium is important because it triggers contractions” of the heart muscle, explained Hake. “We know that 90 percent of all calcium signals come from intracellular storage, and the process that releases this intracellular calcium controls how much total calcium is triggered. We also know that this process is impaired in heart failure. If we can understand this process, we can develop medicine to alter it.”
Hake and his colleagues built a mathematical model of the intracellular volume (dyadic cleft) where calcium enters a cell and triggers additional calcium release in a progress known as calcium-induced calcium release (CICR). They then tried to mimic the processes of a failing and a healthy heart cell and compared their predictions with experimental results.
“The different dynamics of CICR we ran through the model was reconciled with the experimental settings,” Hake remarked. “What happened was a happy cascade where the predictions from our computational model suggested new experiments that experimentalists didn’t think of.”
Arzberger, who co-organized the Institute with Li, said that this ability to quickly and accurately compute complicated biological data will, in time, vastly improve the way that clinicians interact with their patients.
“In the case of the heart, we’ve seen a manifold increase in the ability to compute and get close to a realistic simulation of one heartbeat per second in real time,” added Arzberger, who is a longtime academic participant at the UCSD division of the California Institute for Telecommunications and Information Technology (Calit2). “Because we have better computer models, greater access to computing and, most importantly, data on individual patients that can be fed into the model, within the next five years a clinician will be able to use simulations, almost in real time, as input to whether or not patient will respond positively or not to a particular treatment.”
A second focus of this year’s NBCR Summer Institute was the area of subcelluar modeling, which explores how realistic cell geometry, ion transporter distributions along the sarcolemma and mobile and stationary calcium buffers (including calcium dye) affect subcellular processes. Arzberger pointed to the example of calcium’s role in heart health and its relationship with biological structures called t-tubules, which play an important role in calcium pumping. Anushka Michailova, an associate project scientist in the UCSD Bioengineering Department and co-PI of the NBCR core project “Structurally and Functionally Integrated Modeling of Cell and Organ Biophysics,” presented a paper on the topic at the Summer Institute.
“Up until several years ago, people that modeled the flow of calcium assumed t-tubules were cylindrical in shape,” summarized Arzberger. “But now that we have better geometrical models, it’s become clear that the t-tubules are not uniform, and depending on their shape you have different efficiencies in flow of calcium. We’ve seen in failing hearts that these structures tend to change, so the question now is why? A better understanding of this process will help us come up with diagnoses that could help us restore heart function.”
Computer-aided drug discovery is a third area of focus for NBCR and was a primary research topic at its Summer Institute. University of California, Irvine Assistant Professor of Pharmaceutical Sciences Rommie Amaro presented a lecture on the Relaxed Complex Scheme, which takes a static 3-D crystal structure of a protein and applies molecular dynamics simulations to predict the protein’s movements, thereby exposing previously undiscovered binding sites on the protein where chemicals (pharmaceuticals, for example) can “dock” or bind within the cell.
Also presenting his research at the Institute was University of Florida chemistry graduate student Bill Miller III, who developed a computer script for calculating binding energy using a program called AMBER, or Assisted Model Building with Energy Refinement.
“In drug development, there is a need to calculate binding energy to show how well a drug binds with certain enzymes,” explained Miller. “We created a program that computationally calculates how well something binds without having to spend the money on experimental binding techniques. A lot of HIV drugs have been found by using methods such as this one.”
Arzberger added that a prime motivation for the NBCR computer-added drug discovery research is to apply computational modeling techniques to the area of neglected tropical diseases such as leprosy, river blindness and sleeping sickness.
Remarked Arzberger: “These diseases affect 1 in 6 people and yet the number of drugs developed for them is miniscule because they are in third-world countries that don’t have a large political voice. We want to do anything we can do to automate the process and help the scientists in these countries solve some of these problems.”
Tiffany Fox, (858) 246-0353, firstname.lastname@example.org