The chemistry and biology of the Plasmodium Apicoplast
Why study Plasmodium, causative agent of malaria?
- Enormous disease burden (>300 million cases per year globally; among top 3 infectious killers!)
- Affects the poorest, youngest, and most vulnerable in the global population
The apicoplast: a key anti-malarial target
A great example of Plasmodium's "weird" biology is its plastid organelle, the apicoplast. The discovery of the apicoplast and its function in the parasite has been full of twists and turns.
- Surprise #1. Malaria and other pathogenic parasites contain a relict chloroplast.
- Surprise #2. The apicoplast is essential to the parasite during human infection.
- Surprise #3. In the clinically-important blood stage, the only essential function of the apicoplast is to produce a single metabolite, isopentenyl pyrophosphate (IPP).
We explore intriguing biological questions... with a slight chemical bent.
There is lots to learn. We employ a variety of methods but with a particular focus on the use of chemical tools to overcome the current challenges in studying Plasmodium biology.
- What cellular small molecules and prenylated proteins are constructed from IPP? What are their functions? (metabolic labeling, probes using Click chemistry, proteomics, metabolomics)
- What is the proteome of the apicoplast? How are 100s of nuclear-encoded proteins transported into the 4-membraned apicoplast? (proteomics, organelle isolation)
- How is a single apicoplast faithfully replicated and segregated during multiple fission? (microscopy, inhibitors)