This project aims to develop, implement, and ultimately utilize a cohesive population genetic framework for quantifying the evolutionary forces governing human pathogens. The preliminary aims, focused around TB, are two-fold: first, the biology underlying this bacterial infection requires the development of novel theoretical and statistical approaches, as the clonal nature of the organism, combined with low mutation rates and a lack of recombination, renders tools previously developed for the study of viruses, for example, largely inappropriate. Secondly, novel time-sampled data is being generated from at-risk populations. Together, these preliminary data, will serve as a springboard for the expansion of this collaborative project in to not only other populations hard hit by TB, but also in to other pathogens currently threatening global health.