The Institute for Mathematics and Its Applications (IMA)
by Patrick Nelson, University of Minnesota.

The Institute for Mathematics and Its Applications (IMA), at the University of Minnesota, is currently holding a yearlong program in Mathematical Biology. During the year there will be between 13 and 15 week long workshops dealing with a wide range of topics in the biological sciences. The past month's focus was on three areas related to disease and immunology with sessions on Immune System Modeling, Forging an Appropriate Immune Response and Mathematical Models of HIV. The IMA has taken great pains to bring together leaders in these fields to organize the sessions. The workshops have been a wonderful medium for interaction between experimentalists and theoreticians and in many cases have led to new collaborations. A few days before each workshop a tutorial is held which introduces the terminology and current work in the upcoming areas. This has been a useful opportunity to allow individuals who may be interested in starting research in a specific field to get a brief introduction. The idea of the tutorials is one of many that the IMA has put into effect to optimize the level of understanding of each workshop.

The workshop on Immune System Modeling and Cell Signaling was organized by Byron Goldstein and Alan Perelson, both from the Los Alamos National Laboratory. The general goal of this workshop was to bring together immune system theorists and experimental immunologists with mathematicians who can become stimulated by this exciting and important area, and who may be able to make an impact by contributing new methods and tools of analysis. The main themes of this workshop can be broken down into: how do cells of the immune system receive and send signals; what are the dynamical interactions among B cells, T cells, and antigen presenting cells, and the regulation of these populations; what are the dynamics of the formation of germinal centers, somatic mutation and affinity maturation.

The workshop on Immunology attracted participants from many parts of the world and provided the resident post-docs a wonderful medium for developing new collaborations. The workshop had many excellent talks. To highlight a few: Henry Metzger from the NIH spoke about signal transduction by the FceRI, a class of immunoreceptors, and discussed the analysis of the early events. Mark Jenkins from the University of Minnesota discussed tracking the interactions between antigen specific T and B cells in situ and Byron Goldstein spoke on aggregating receptor systems.

The following week Lee Segel, from the Weizmann Institute of Science, and Stephanie Forrest, from the University of New Mexico, organized a workshop called ``Forging an Appropriate Immune Response as a Problem in Distributed Autonomous Systems''. The main theme dealt with how the vast collections of cells and molecules that comprise the immune system self-organize to provide appropriate responses to the wide variety of evolving pathogens that attack the organism during its lifetime. One very interesting area of this workshop discussed the application of immune system principles to computer security against 'viruses' and other intrusions. The organizers invited researchers from IBM and the computer science department of the University of New Mexico who specifically talked about this exciting area. Other researchers presented discussions on T cell activation, antigen presentation and processing, MHC complexes, cytotoxic T cells, and on how spatial organizations can allow non-specific signals to select specific immune elements that contribute to system goals. The workshop ended with a dinner at a local restaurant, which allowed the participants an opportunity to discuss ideas in a more relaxed manner.

After a one-week break, a new workshop began focusing on dynamics and control of AIDS. This workshop was organized by Denise Kirschner from the University of Michigan and Alan Perelson and focused on modeling HIV pathogenesis and the complex interaction of HIV with the immune system. One of the hallmarks of AIDS is the decline in CD4+ T lymphocytes. After potent antiviral drugs are given, the concentration of HIV in blood and the lymphoid tissue declines and T cell populations recover. The workshop examined models of disease progression and therapy that include the kinetics of lymphocyte production and lymphocyte movement during both disease and remission. The modeling of HIV can be broken down into four categories: HIV progression, which is defined from initial infection until the onset of AIDS, drug treatment models, vaccines and epidemiology, and mutation. In the past few years, models combined with experimental results have assisted in revealing many of the complicated dynamics of the disease. The workshop brought together leading modelers and experimentalists and provided a forum for presenting new results.

The workshop started with Alan Perelson presenting an overview of the landmark work he has done in collaboration with David Ho, of the Aaron Diamond AIDS Research Center. Two of the leading experimentalists in the study of HIV, George Shaw from the University of Alabama at Birmingham and Ashley Haase from the University of Minnesota, were present and gave fascinating talks on cutting edge research. There were talks examining the initial stage of infection with hopes of trying to understand the long latent phase seen in most HIV infected individuals. Other participants, including Sally Blower from the University of California at San Francisco, gave expositions about the epidemiology of the disease and discussed the use of vaccines and their predicted success or failure. Drug treatment strategies are becoming increasingly complicated since the introduction of combination therapy and researchers presented colorful talks on the applications of drug perturbation models and their results. The workshop's best asset was its generation of discussion and comments on the presented work which in many cases led to a new understanding of the modeling process.

These workshops have been stimulating, exciting and have led to scientific advancement. I have presented only a brief overview of each workshop. A complete listing of all the talks and abstracts from the previous workshops as well as the upcoming areas of concentration can be found on the IMA web site. We are entering a new and exciting era of research in mathematical biology. I would like to end with a quote from the IMA web page: ``A century of research has elucidated fundamental mechanisms in evolution, collective phenomenon and pattern formation, and laid the foundations for more specialized modeling; and the development of new computational tools has greatly expanded the potential both for fundamental studies and for communication.''

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