Mathematics used to discern immune response to infectious diseases

December 08, 2005

The National Institutes of Health (NIH) has awarded the University of Pittsburgh School of Medicine a five-year, $9.1 million contract to develop sophisticated mathematical models for investigating how the immune system responds to the pathogens that cause flu, tuberculosis (TB) and tularemia, an especially dangerous infection that some authorities believe could be used as a biological weapon. Such models should help expedite the development of vaccines and therapies against these and other infectious agents and help researchers and public health officials in their efforts to predict or prevent disease outbreaks as well as determine the best courses of treatment.

The contract establishes Pitt as an Immune Modeling Center, one of four supported by the NIH's National Institute of Allergy and Infectious Diseases (NIAID), and takes advantage of Pitt's existing collaborations with Carnegie Mellon University and the University of Michigan.

"This center's work will draw upon our expertise in mathematical modeling of the immune system as well as our knowledge about immunity to infectious diseases. Working as a team of immunologists, computational biologists, computer scientists and mathematicians, our goal is to capture the complexity of the immune system through mathematics," said Penelope A. Morel, M.D., associate professor of immunology and medicine at the University of Pittsburgh School of Medicine and principal investigator of the Pitt-based Immune Modeling Center. Shlomo Ta'asan, Ph.D., professor of mathematics in Carnegie Mellon's Mellon College of Science, is co-principal investigator of the center.

The Immune Modeling Center will focus on understanding the innate, or natural, and adaptive immune responses to influenza A virus, Mycobacterium tuberculosis, which causes TB, and Francisella tularensis, the bacterium responsible for tularemia. Since each of these organisms enters the body via the lung, the investigators will study the specific immune cells recruited to the lung and identify the particular genes expressed and the molecules produced in response to infection. A combination of mathematical and animal models will be employed to test different vaccine and therapeutic strategies, including a novel approach that aims to enhance immune response through certain proteins called cytokines.

"Mathematical modeling has tremendous potential to help improve the safety and efficacy of vaccines as well as to facilitate prediction of outcomes and prevention and treatment of emerging and re-emerging infectious diseases. One of the advantages of generating a computerized mathematical system that mimics how our immune system responds to specific pathogens is its use for conducting meaningful studies with minimal use of the infectious agents themselves," explained Dr. Morel.

Studies focused on developing models of the immune response to TB will be headed by JoAnne L. Flynn, Ph.D., department of molecular genetics and biochemistry, University of Pittsburgh School of Medicine, and Denise Kirschner, Ph.D., a mathematician in the department of microbiology and immunology at the University of Michigan.

Gerard J. Nau, M.D., Ph.D., also of the School of Medicine's department of molecular genetics and biochemistry, will lead the project modeling the immune response to tularemia. That project also includes the University of Michigan's Dr. Kirschner and Dr. Ta'asan from Carnegie Mellon.

Modeling of flu virus infection and immunity will be undertaken by Ted M. Ross, Ph.D., division of infectious diseases, department of medicine, University of Pittsburgh School of Medicine; and Dr. Ta'asan of Carnegie Mellon.

At Pitt, Dr. Morel is leading a project focused on modeling the innate immunity of the lung, which also includes from the University of Pittsburgh School of Medicine: Dr. Nau; Russell Salter, Ph.D., department of immunology; and Takis Benos, Ph.D., department of computational biology; and from Carnegie Mellon, Benoit Morel, Ph.D., of the College of Engineering and Ziv Bar-Joseph, Ph.D., of the School of Computer Science.

The Immune Modeling Center contract includes a bioinformatics component for managing the data generated by each project and developing a Web-based collaboration platform that will allow investigators from other institutions to access data and use the models developed over the next five years. Leading this effort are Panos K. Chrysanthis, Ph.D., and Alexandros Labrinidis, Ph.D., both of the department of computer science, University of Pittsburgh School of Arts and Sciences. An educational program that will focus on the value of using mathematical approaches to the understanding of immunological processes will be developed by Drs. Ta'asan, Kirschner and Penelope Morel.

The other institutions receiving NIAID contracts to support Immune Modeling Centers are Duke University, the University of Rochester and Mount Sinai School of Medicine.

University of Pittsburgh Medical Center

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