Malaria parasite drug target

Candidate—Ellen Yeh, UCSF

Nominated by Joe DeRisi, UCSF

The Deloitte QB3 Award for Innovation recognizes a graduate student, postdoc, staff scientist, or team from UC Berkeley, UC Santa Cruz, or UCSF who has made an advance with the capacity to improve human health. Candidates for were nominated by QB3 faculty. Finalists were chosen by a panel of expert judges.

We asked each nominee (or team) to answer a series of short questions, to give a snapshot of their project. Read their answers below. Leave a comment to let us know what you think!

Ellen Yeh, MD, PhD. Photo: Jason Bardi, UCSF Public Affairs

Please describe your innovation.
Malaria-causing Plasmodium spp parasites contain an essential plastid organelle, the apicoplast, which is a key target for the development of anti-malarials. However, nearly 20 years after its discovery, the essential functions of the apicoplast remain a mystery. We use a simple chemical method to generate parasites that have lost their apicoplast, normally a deadly event, but which are “rescued” by the addition of a single essential metabolite. These apicoplast-minus parasites demonstrate that, surprisingly, the apicoplast has only one essential function during blood-stage infection, namely isoprenoid precursor biosynthesis. This finding has important implications and utility for therapeutic development.

Within the 140-character Twitter limit:

What’s the impact?
With 300 million cases and 1 million deaths per year, #malaria disproportionately affects the world’s poorest and youngest,

What’s the novelty?
We got freaky parasites missing an essential organelle, “rescued” by +ing just 1 metabolite! 20yof ?s —>wacky biology, life-saving therapy

What’s the utility?
Instantly defines druggable pathways AND easy specific drug screen. Ready to test as attenuated vaccine which improves on what’s available

In the malaria parasite, the ‘apicoplast’ normally segregates certain metabolites (left). Knocking out the apicoplast (right) removes the ability to segregate, and kills the parasite—because its survival depends on a single chemical produced by the apicoplast.

How does your research topic represent a strong advance in human health? And how will it influence the way we operate in science in the future?
Malaria is a profound human health problem that has shaped our evolutionary past and continues to influence modern day with a disease burden that disproportionately affects the world’s poorest and youngest. New anti-malarials are desperately needed in the face of existing or emerging drug resistance to all available therapies, while an effective vaccine remains elusive. Apicoplast-minus parasites define the essential pathway in the apicoplast and provide a pathway-specific screen to immediately begin identifying drugs that specifically target this essential function. Moreover, apicoplast-minus parasites are a potential attenuated vaccine strain with significant advantages over current vaccine technologies.

Reference:
Chemical Rescue of Malaria Parasites Lacking an Apicoplast Defines Organelle Function in Blood-Stage Plasmodium falciparum
Ellen Yeh and Joseph L. DeRisi
PLoS Biol 9(8): e1001138. doi:10.1371/journal.pbio.1001138