Laws of mechanics and function in proteins as evolved molecular machines

项目总结/文摘

PROJECT SUMMARY/ABSTRACT The adaptive immune system has evolved to remember primary exposures to specific antigens and launch effective attacks to subsequent exposures. However, rapidly evolving viruses like influenza and HIV present new challenges to the human immune system as they mutate, making them harder to recognize and respond to during subsequent exposures. In order for secondary responses to these pathogens to succeed, the primary response must generate a memory response that balances specificity to the original antigen with diversity against the multitude of possible variants of subsequent exposures. For an individual of a given species interacting with other individuals within a larger population, the efficacy of a given balance between specificity and diversity depends on a number of factors, including how likely the individual is to be exposed to the same pathogen in the future, the rate at which the antigen is mutating, and constraints on the biological processes which control the generation of immunological memory within that species. This research program aims to construct a theoretical framework for characterizing the benefits and trade-offs associated with diversity in the adaptive immune response and the mechanisms by which said diversity is generated. This study will then use computational analyses of several datasets to evaluate the extent to which the antibody responses of different species generate levels of diversity which are well-adapted to their biological needs, using mice and humans as representative examples.