The Miller Hypothesis.

The immune response is a cornerstone in the body's struggle against microbial pathogens. In ways that we do not yet completely understand, the mammalian immune response has evolved to identify proteins of pathogens that are either important virulence factors or key immunoprotective targets. Professor James N. Miller suggested that one way to discover such proteins is to harness the power of the immune system in the laboratory.This general concept, referred to here as the Miller Hypothesis, took several different manifestations in the discovery of some of the best known and widely studied leptospiral proteins: The porin OmpL1 was identified by surface immunoprecipitation, leptospiral immunoglobulin-like proteins were uncovered by screening a genomic library with sera from leptospirosis patients, and the major outer-membrane lipoprotein LipL32 was recognized through immunoblot studies. Such approaches will continue to bear fruit for both the leptospiral research field and research on other invasive pathogens.