UC San Diego

HIV/AIDS, malaria, and tuberculosis are the world’s three deadliest infectious diseases of humans, often referred to as the ‘Big Three’. Together, they are responsible for more than 10% of all the deaths worldwide each year. What is perhaps most worrisome is the fact that the current therapies that treat

these conditions are losing their efficacy due to the emergence of antimicrobial drug resistance. Accordingly, research is urgently needed to address the growing problem of drug resistance and to help drive the development of novel therapeutics. In the first chapter of this doctoral dissertation, three strategies to combat drug resistance are discussed: 1. Developing therapeutics that target host-derived factors, 2. Identifying new antimicrobial inhibitors, and 3. Investigating host-pathogen biology using systems analysis to drive the development of novel therapeutics. Examples of research utilizing these strategies are discussed in the following chapters, with a particular focus on two of the “Big Three” pathogens- HIV-1 and the malaria parasite, Plasmodium. The identification and characterization of a novel host factor that regulates HIV-1 reverse transcription is described in Chapter 2. In Chapter 3, the development of a high-throughput phenotypic assay to identify novel antimalarial drugs is discussed, and in Chapter 4, a broad review of systems biology-based research of host-parasite interactions (with an emphasis on Plasmodium) is included. The Appendix includes preliminary data and future aims for systems biology research aimed at understanding Plasmodium liver-stage development. Through the combination of these scientific efforts, we will surely strength our position in the ongoing battle against antimicrobial drug resistance.