Gene regulation in Plasmodium falciparum

  • Project Leader

    Dr Stuart Ralph
    T: +61 3 8344 2284
    E: saralph@unimelb.edu.au
    Location: Bio21 Institute, 30 Flemington Rd, Room: 335, Lab: 312

Project Details

Gene regulation in Plasmodium falciparum

Plasmodium falciparum successfully evades the human immune system by an ingenious trick of constantly changing the surface coat to avoid detection and destruction mediated by human antibodies. This constant surface transformation is referred to as antigenic variation, and is controlled by a fascinating mechanism of genetic regulation. Many of the regulatory processes involved in this mechanism are epigenetic processes, dependent on covalent modifications of the nucleosomes that serve as a scaffold for DNA wrapping.

transmission electron micrograph showing Plasmodium falciparum parasite

Figure 1: This false-colored transmission electron micrograph shows a P. falciparum parasite, cause of the most severe form of malaria. Antigenic variation in these parasites contributes to parasite immune evasion, and compartmentalisation of silencing factors and chromatin states in the nucleus play important roles in regulating antigenic variation. In this image, the infected erythrocyte is shown in red, and the parasite is shown in purple. The dark blue highlights the condensed material at the nuclear periphery with lighter blue displaying the nuclear core

Projects

1. Chromosomal compartmentalization

Genetic elements within and adjacent to genes help regulate the covalent modifications of the nucleosomes to which they are attached. These elements also delineate where one nucleosome-modification zone ends and where the next begins. This is a phenomenon that has been very poorly studied in any microbe, but is extremely important for understanding how some genes are highly activated while others are stringently silenced. We have established genetic screens to identify these elements in P. falciparum, and will identify the proteins that recognise these elements.

2. Upstream elements regulating transcription

While much is known about the genetic elements that regulate transcription in some model organisms, transcriptional promoters are only vaguely understood in Plasmodium. The complete sequencing of the Plasmodium genome, combined with a number of whole-genome microarray experiments, now provide us with an opportunity to identify the elements that regulate timing and abundance of Plasmodium transcription. This project will combine bioinformatic analyses with parasite genetic transfection experiments to characterise transcriptional regulation.

Apicomplexan cell biology

Apicomplexan parasites possess novel organelles and cell biological structures, some of which are adaptions to intracellular parasitism, while others are vestiges of their evolutionary past. We are interested in understanding protein trafficking to the various compartments of apicomplexan parasites, and are developing bioinformatic tools to catalogue and predict protein subcellular localisation in apicomplexan parasites such as Plasmodium.

Research Group

Ralph laboratory: Drug targets and gene regulation in Plasmodium falciparum



Faculty Research Themes

Infection and Immunology

School Research Themes

Infection & Immunity, Molecular Mechanisms of Disease



Key Contact

For further information about this research, please contact the research group leader.

Department / Centre

Biochemistry and Molecular Biology

Unit / Centre

Ralph laboratory: Drug targets and gene regulation in Plasmodium falciparum