WEHI Wednesday Seminar hosted by Professor Alan Cowman
 

Dr Danushka Marapana

Senior Research Officer – Infection and Global Health division, WEHI

An E3 ubiquitin ligase controls sexual stage differentiation in human malaria parasites

 

Davis Auditorium

Join via SLIDO enter code #WEHIWednesday

Including Q&A session
 

The human malaria parasite Plasmodium falciparum undergoes dramatic changes to its cellular morphology and physiology allowing it to transition between disparate cellular niches within the human and mosquito hosts. The only parasite forms that can be transmitted from the human to the mosquito facilitating the spread of disease are sexually dimorphic cells known as gametocytes. The molecular mechanisms underpinning gametocyte development is a nexus of keen interest as it represents a developmental bottleneck that could be exploited to block transmission.

A metabolite-based CRISPR screen in the related apicomplexan parasite Toxoplasma gondii identified the parasite-expressed Glucose Induced Degradation (GID) E3 ubiquitin ligase complex as a critical factor in parasite transition between the actively dividing tachyzoite and latent bradyzoite stages. In this work we investigate the function of the Plasmodium falciparum GID complex.

The PfGID E3 ubiquitin ligase complex is a central regulator of sexual development in P. falciparum, and controls a sophisticated system integrating protein degradation and RNA regulation. Disruption of the PfGID complex leads to severe impairment of gametocyte maturation that blocks parasite transmission to mosquitoes, underscoring its pivotal role in the parasite life cycle. We identified that the PfGID E3-ligase complex ubiquitinates and degrades proteins critical for gametocyte development and transmission. These PfGID substrates and their timely regulation function in fine tuning gametocyte development and link a previously unidentified translational repression complex and a male gametocyte development program in human malaria parasites.

These findings illuminate the intricate molecular choreography underlying Plasmodium gametocyte development and provide insights into how single-celled eukaryotes execute cell fating programs that allow them to navigate complex life cycles and adapt to diverse host environments.

All welcome!