Investigating novel chromatin proteins of the malaria parasite P. falciparum as drug targets.

Research Opportunity
PhD students, Masters by Research, Honours students, Master of Biomedical Science
Department / Centre
Microbiology and Immunology
Location
Doherty Institute
Primary Supervisor Email Number Webpage
Dr Michael Duffy mduffy@unimelb.edu.au 8344 3262 Personal web page
Co-supervisor Email Number Webpage
Dr Lee Yeoh

Summary Plasmodium falciparum has novel bromodomain proteins that are involved in creating chromatin structure and gene regulation. We will characterise these proteins as potential drug targets.

Project Details

Plasmodium falciparum has novel bromodomain proteins that are involved in creating chromatin structure and gene regulation. We will characterise these proteins as potential drug targets.

The malaria parasite Plasmodium falciparum caused the deaths of approximately 435,000 people in 2017, most of whom were children. P. falciparum multiplies inside our red blood cells and bursts out every 48 hours and then rapidly re-invades fresh red blood cells. Resistance is emerging to our best anti-malarial drugs so new drugs are urgently needed. A promising strategy is to target proteins that are found in P. falciparum but not humans. P. falciparum employs novel chromatin proteins to regulate gene expression in its pared back genome.

Bromodomain proteins (BDPs) bind to acetylated lysine residues on histones within nucleosomes and then can either recruit complexes that further modify chromatin, or recruit transcription factors that directly regulate transcription. Bromodomain inhibitors have shown promise in treating cancer. P. falciparum has 8 novel BDPs, we recently showed that one was an essential regulator of genes required for parasite invasion of erythrocytes (Josling A et al Cell Host Microbe 2015). We have now made recombinant parasites that can be induced to knockout and/or knockdown BDPs. From these parasites three more BDPs are essential whilst two are not required for blood stage survival. All of these BDPs will be assessed for their role in regulating parasite gene expression by RNAseq, their genomic location by ChIPseq, and their functional role in parasites by assessing parasite growth and various parasite phenotypes, e.g. erythrocyte invasion and transition to sexual, transmissible forms. BDPs that have essential, functional roles could be promising, novel drug targets.



Faculty Research Themes

Infection and Immunology

School Research Themes

Infection & Immunity



Research Opportunities

PhD students, Masters by Research, Honours students, Master of Biomedical Science
Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research

Graduate Research application

Honours application

Key Contact

For further information about this research, please contact a supervisor.

Department / Centre

Microbiology and Immunology

Research Node

Doherty Institute

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