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November 15, 2010

Researchers battle bioterrorism threat with $11.9 million award


Flu viruses are a great threat, whether they stem from Mother Nature or are modified by humans to create a deadly bioweapon. The Medical Center will tackle both scenarios with a five-year contract, totaling approximately $11.9 million, from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The contract will further research into how scientists can use computer modeling to find ways of boosting human immune responses against and identify new areas of investigation into treatments for a variety of potentially lethal viruses.  

“This type of research is extremely important because it is going to make the United States better, stronger, and faster at developing new vaccines and therapies for flu infections that we don’t yet have vaccines for,” says Martin Zand, codirector of the Center for Biodefense Immune Modeling and medical director of Kidney and Pancreas Transplant Programs at the Medical Center.

Throughout the five-year contract, researchers will design mathematical models and simulation tools to study how the immune system responds to flu vaccines, attempting to uncover why some people have a good response to a vaccine and others don’t. Using data from mice and humans, they hope to use these models to simulate different flu scenarios and test medical interventions that might be developed to limit the extent of a dangerous flu infection in people.

“The wonderful thing about models is that we can get some idea of how a virus might evade the immune system, how the immune system might respond, and how we can enhance the immune response without ever having to create or live through a pandemic or bioterrorist attack,” Zand says.

The contract is a five-year renewal of the Center for Biodefense Immune Modeling at the Medical Center, which was initially funded with a $10 million contract in 2005 as part of NIAID’s Modeling Immunity for Biodefense program. Researchers spent the past five years developing models of different flu infections, and now they will use this knowledge to further model and study animal and human immune responses to new and existing flu vaccines. 

In addition to the modeling and experimental work, the contract will fund development of new mathematical approaches and software tools that will be made available to the entire research community.

This NIH program differs from past NIH-funded immunology research by its emphasis on mathematical modeling, combined with cutting-edge immunology experiments and the development of new computational tools for immunology research. Such approaches allow scientists to look at the behavior of the whole immune system over time, as opposed to getting a snapshot of one or two points in time, such as after someone is vaccinated or infected with the flu. Researchers believe this more comprehensive and mathematically based approach will yield greater understanding of how the flu and other viruses attack the body, how the immune system reacts, and how we might be able to intervene.

“Using models and simulations is commonplace in many industries, such as the auto and airline industries, where manufacturers test designs before they actually produce cars and planes,” says Hulin Wu, co-director of the Center for Biodefense Immune Modeling and a professor in the Department of Biostatistics and Computational Biology at the Medical Center. “Biomedical research has adopted this same way of doing business, using models to gather information that will help scientists design the most effective vaccines and therapies in the shortest amount of time.”

Wu adds that models are essential because many immunology experiments can’t be done in a lab: “We can’t infect people with a new strain of the flu virus, but we can use a mathematical model of a human in the computer to learn more about the virus and test potential therapies.”
Biomedical research that integrates methods and techniques from mathematical modeling, biocomputing, biostatistics, and bioinformatics is an emerging discipline known as systems biology, and is helping fuel biomedical science discoveries in the new century. Wu and Zand are utilizing a systems biology approach to help guide their research.

An example of a study Wu and Zand will begin this year involves collecting blood samples from small groups of people each day, for 11 days after they receive the seasonal flu vaccine. Each day, these samples will be analyzed in a battery of cutting-edge cell, protein, and gene expression tests. The research team will do a similar study in mice and compare the human and animal data to garner valuable information about where antibodies or immune cells are and when, what genes are expressed in different places and what cellular markers are present following vaccination: The detailed data will be used to create models that predict responses to current and future flu vaccines in mice and, possibly one day, in people.

In addition to Zand and Wu, John Treanor, David Topham, Tim Mosmann, Stephen Welle, Alexandra Livingstone, Mark Sangster, Luis Martinez-Sobrido, Brian Ward, Hongyu Miao, Hua Liang, Gregory Warnes, Jingming Ma, Anthony Almudevar, and Jeanne Holden-Wiltse from the Medical Center are involved in the research. Alan Perelson and Ruy Riberio of the Los Alamos National Laboratory are also part of the research team.

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