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Diego Huet

Blurred image of the arch used as background for stylistic purposes.
Adjunct Assistant Professor

Apicomplexans are protozoan parasites that cause more than half a million deaths every year. During their life cycles, these pathogens are able to survive in different environments, as they enter and exit host cells, and transfer between hosts. Their ability to propagate within distinct niches demonstrates their metabolic plasticity, and although this ability is crucial for parasite survival, its underlying mechanisms remain poorly understood. Our research program aims to comprehensively map divergent metabolic pathways involved in the metabolic plasticity of apicomplexans. To do so, we use Toxoplasma gondii, a model to understand the conserved aspects of apicomplexan biology.

Within mitochondria, the enzyme ATP synthase plays crucial roles in metabolic plasticity, and its activity is regulated through different mechanisms. In apicomplexans, important metabolic pathways take place within their single mitochondrion. However, the mechanisms regulating the apicomplexan ATP synthase activity remain poorly understood. Surprisingly, more than half of the subunits of the apicomplexan ATP synthase are only found in these organisms, raising the question of whether these subunits could be involved in the regulation of the complex. We aim to define the function of those subunits, and determine the regulatory mechanisms behind the apicomplexan ATP synthase.

We will also characterize the role that organelles play in the metabolic plasticity of apicomplexans. In other eukaryotes, organelles can exchange metabolites with each other via regions termed membrane contact sites (MCSs). We aim to identify the molecular effectors, which we hypothesize are MCSs, linking the mitochondrion and the apicoplast, an apicomplexan-specific organelle involved in lipid homeostasis. Identifying MCSs between the mitochondrion and apicoplast will reveal apicomplexan-specific adaptations, providing new opportunities for designing treatments against these pathogens.

1.         Usey MM, Huet D. Parasite powerhouse: A review of the Toxoplasma gondii mitochondrion. J Eukaryot Microbiol. 2022 Mar 21;e12906.

2.         Huet D, Rajendran E, van Dooren GG, Lourido S. Identification of cryptic subunits from an apicomplexan ATP synthase. Elife. 2018 Sep 11;7:125.

3.         Sidik SM, Huet D, Lourido S. CRISPR-Cas9-based genome-wide screening of Toxoplasma gondii. Nat Protoc. 2018 Jan 11;13(1):307–23.

4.         Sidik SM*, Huet D*, Ganesan SM, Huynh MH, Wang T, Nasamu AS, Thiru P, Saeij JPJ, Carruthers VB, Niles JC, Lourido S. A Genome-wide CRISPR Screen in Toxoplasma Identifies Essential Apicomplexan Genes. Cell. 2016 Sep 8;166(6):1423–35.e12.

 

Professional Website:

https://huetlab.com/

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