Alternative splicing in human parasites

Project Details

Next generation sequencing has revealed that an unexpectedly high proportion of mammalian genes undergo alternatively splicing to produce multiple transcript isoforms.

diagram showing alternative splicing
Figure 1: Some precursor mRNAs (pre mRNA) can undergo alternative splicing to produce diverse mature transcripts. This can result in altered exon boundaries, or even skipped introns or exons. In some cases this results in the production of multiple protein variants.

We have recently shown that alternative splicing is also widespread in the human parasites Plasmodium (causative agent of malaria) and Toxoplasma, (causative agent of toxoplasmosis). We are now investigating whether this mechanism is necessary for parasites differentiating between human and invertebrate life-stages. We will apply novel long-read sequencing techniques to establish the impact of alternative splicing on whole transcripts in a variety of human and veterinary parasites. We will also investigate the implications of alternative splicing on generation of proteome diversity. This is a collaborative project with Associate Professor Aaron Jex at the Walter and Eliza Hall institute of Medical Research.

diagram showing the effect of alternative splicing
Figure 2: The Plasmodium cysteinyl tRNA synthetase gene produces transcripts that are alternatively spliced to produce protein variants with different N-termini. One variant is targeted to the parasite’s plastid while another variant is targeted to the parasite’s cytosol.

Collaborators

Associate Professor Aaron Jex, Walter and Eliza Hall institute of Medical Research

Funding

This is a collaborative funded by a discovery project grant from the Australian Research Council (Grant DP160100389)

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, Systems Biology



Key Contact

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

Department / Centre

Biochemistry and Molecular Biology