There are many challenging problems at the interface of computer science and many other fields. Recently computer scientists have contributed extensively to areas such as DNA sequence assembly, sequence analysis, protein-protein interactions and intra-cellular signal communication. However, there are many system-level biology areas which are ripe for inter-disciplinary approaches. This proposal explores one such area - the immune system. In response to a microbial infection, the immune cells which are highly specific to small structural components of the microbe get activated. The process by which this highly parallel search gets accomplished will be studied. Another challenging problem is the process by which the immune cells develop tolerance. Such a study will be useful in understanding how malignant cells become immortalized evading the immune cells. Intellectual Merit The proposed research will provide a theoretical foundation to very important immunological phenomenon. New search algorithms based on spatial and temporal aspects require development of new theoretical tools. Broader Impacts New breakthroughs in cancer treatment will depend upon rapid advances in immunology. Even though generic treatments for cancer (radiation treatment for localized forms and chemotherapies for metastatic forms) will continue to play dominant roles in cancer treatment, more targeted antibody and other immunological modalities will become more widely used. These will have potentially fewer side effects compared to generalized chemotherapies. A better understanding of the immune responses could result in new approaches for coping with spam, phishing and viral attacks of computer systems. A-1
