Award details

Plastid-to-nucleus signalling in Plasmodium

Reference	BB/E004393/1
Principal Investigator / Supervisor	Professor Christopher Howe
Co-Investigators / Co-Supervisors
Institution	University of Cambridge
Department	Biochemistry
Funding type	Research
Value (£)	100,127
Status	Completed
Type	Research Grant
Start date	01/09/2006
End date	29/02/2008
Duration	18 months

Abstract

Plasmodium and many other apicompexan pathogens have a remnant chloroplast (plastid), the apicoplast, which is essential for the cell's survival. The apicomplexan plastid has a remnant genome encoding an iron-sulphur cluster biosynthesis protein, a chaperone, and components of the transcription and translation machinery. The majority of apicomplexan plastid proteins are nuclear encoded, synthesized in the cytosol and imported into the plastid. It is known that in plants and algae, the chloroplast signals its metabolic state to the nucleus, and this affects the expression of nuclear genes for chloroplast proteins. We believe that this is likely to happen with the apicomplexan plastid, and propose a pilot project to test this. If successful, this will lead to a application for support for a full three-year project. In experiments analogous to those used successfully with plants, we will treat Plasmodium cells at a range of stages in the growth cycle with inhibitors of (i) plastid protein synthesis and (ii) a plastid metabolic pathway. We predict that plastid-to-nucleus signalling will lead to changes in levels of mRNAs from nuclear genes for plastid proteins, and we will test this using molecular biological techniques. We will use microarrays to determine which genes are most affected. Agents that interfere with the signalling process will have potential as antimalarials.

Summary

Malaria is caused by a single-celled parasite. Very surprisingly, the ancestors of this parasite (and related ones like Toxoplasma, which can also cause disease) were photosynthetic. Like plants and algae, their cells contained chloroplasts, the site of photosynthesis. Although Plasmodium is no longer photosynthetic, it still has the remains of the chloroplast, called the apicoplast, and this is essential for the parasite to live. Many drugs for malaria, such as clindamycin, work by interfering with the the Plasmodium chloroplast. Many of the proteins in the chloroplast are made elsewhere in the cell, from genes present in the nucleus, and imported into the chloroplast after they have been made. We believe that the chloroplast can send a signal to tell the nucleus when it needs these proteins, and we want to test this idea. We know that something similar happens with the chloroplasts of plants and algae, so we know how to test it with Plasmodium. If we can show this signalling happens, we can start to understand how to interfere with it - and this may lead to new drugs for treating malaria.

Committee	Closed Committee - Plant & Microbial Sciences (PMS)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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