Reprogramming of the Trypanosoma brucei Epigenome during Human Infection: Opportunities for New Therapies
T. brucei is a single-celled trypanosome that occurs in extensive parts of sub-Saharan Africa, and causes African sleeping sickness. Hundreds of thousands of individuals suffer from this disease. We plan to study the way in which the epigenome of this organism is used to allow this trypanosome to continually evade the human immune system. The epigenome of an organism represents heritable information that is encoded outside of the nucleotide sequence of its genome, and is formed by the components that package the DNA inside the cell nucleus, and modifications of the DNA molecule itself. The epigenome is an essential interface that helps to control the genetic function of DNA, and misregulation of the epigenome is responsible for many serious human diseased states, including cancer, myotonic dystrophy and autism spectrum disorders. The epigenome thus represents a potent therapeutic target, and several compounds that interfere with proteins that recognize or that confer specific histone modifications have either received FDA approval or are undergoing clinical trials. These compounds hold a tremendous promise for the treatment of diseases such as leukemia. In this project we hope to identify epigenetic targets for the development of future drugs to treat African sleeping sickness more effectively.