WEHI Wednesday Seminar hosted by Professor James McCarthy
 

Dr Matthew Dixon
Senior Research Fellow in the Department of Infectious Diseases, Doherty Institute, University of Melbourne and in the Immunity Division at WEHI

Protein-Transcript decoupling drives Plasmodium falciparum sexual development

Davis Auditorium

Join via SLIDO enter code #WEHIWednesday

Including Q&A session

Dr Matthew Dixon is co-appointed as a Senior Research Fellow in the Department of Infectious Diseases, Doherty Institute, University of Melbourne and in the Immunity Division at WEHI. He leads a research program focused on understanding the biology of malaria parasite sexual development and co-leads the development of human challenge models to test malaria transmission blocking interventions with Prof James McCarthy.

The transmission of malaria from the human host to the Anopheles mosquito vector requires the formation of specialised male and female parasites, known as gametocytes. Young Plasmodium falciparum gametocytes home to and sequester in the bone marrow and spleen for up to 12 days before re-entering the circulation ready for uptake by mosquitoes. During this time, they dramatically remodel their morphology, physiology and metabolism supporting their survival in the host and readying themselves for mosquito stage development. Despite the importance of these pathways to gametocyte development and transmission, we lack a detailed understanding of how these complex biological programs are regulated.

To identify the underlying mechanisms controlling the expression of the key biological programs, we generated a high-resolution molecular atlas of P. falciparum gametocytes by integrating time-matched transcriptomic and proteomic data from across gametocyte development.  Our analysis reveals for the first time, a tightly programmed global decoupling of transcription and translation that regulates the coordinated transition of early to late-stage gametocyte development. This decoupling event is characterised by rapid ubiquitin-mediated degradation of hundreds of proteins required for early gametocyte development with the release and translation of previously repressed transcripts encoding hundreds of proteins essential for late-stage differentiation and sexual maturity. Finaly, we show that conditional deletion of genes controlling this decoupling ablates gametocyte development and transmission.

This work defines a new mechanism of developmental regulation in an early eukaryote and describes new biology that could be targeted to block gametocyte development and parasite transmission.

All welcome!