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Evaluating Translation as an Antimalarial Target

  • Author(s): Garcia, Valentina Elizabeth
  • Advisor(s): DeRisi, Joseph
  • et al.

As the primary cause of severe malaria, P. falciparum is a vexing parasite that has had profound effects on humanity for centuries. To continue to fight towards the global eradication of malaria, novel treatments must be employed. These therapeutics can be developed through two different means. Already existing compounds can be screened for specific activity against the parasite, or drugs can be designed to target unique parasite biology. Both are powerful potential methodologies; however, both also require a deeper understanding of parasite biology. Here, we take both approaches to explore translation as a potential therapeutic pathway. We start in chapter 2 with tool development that aided our ability to scale up our studies. In chapter 3, all commercially available antimalarials were screened for an effect on translation. In chapter 4, synthetic derivatives of Virginiamycin M2 were screened for activity against P. falciparum growth and in vitro translation. In chapter 5, we reversed our approach by studying the mechanisms of translation initiation in P. falciparum and compared the results to human. Finally in bonus chapter 6, we take a sharp turn to zoonotic disease and look at the differential effects of reptarenavirus infection on boa constrictors and ball pythons.

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