Amandine Guérin
“Host manipulation by the parasite Cryptosporidium”
Lecture
The infection by the parasite Cryptosporidium is a leading cause of child mortality, no vaccine is available and the current drug treatment against this diarrheal pathogen is inefficient. The disease is transmitted through food or water contaminated with oocysts, the chlorine-resistant parasite stage. The parasite infects the epithelial cells of the small intestine in which it replicates intracellularly. Invasion and intracellular development require extensive modifications of the host cell that remain largely unknown at the molecular level. We recently showed that parasite secreted proteins play an important role in this process, however, our knowledge remains limited. Modifications of the enterocytes as well as persistent inflammation will alter the physiology of the gut and can have long lasting impact on the children. We conducted a proteomic experiment, hyperLOPIT, on fractionated Cryptosporidium sporozoites to identify the content of the various secretory organelles. This list of potential Cryptosporidium virulence factors will help fill important gaps in our knowledge of the host/parasite interplay.
Biography
Amandine Guérin obtained her bachelor’s and master’s degree in microbiology from the University of Bordeaux in France. She then pursues her work at the University of Montpellier where she obtained her PhD in 2017 with the support of two French fellowships, ParaFrap and FRM. Her work in Dr. Maryse Lebrun laboratory was to investigate the invasion mechanism of the parasite Toxoplasma gondii, specifically how parasite secreted proteins hijack host mechanisms1-2. This work was an important step toward understanding the role of the RON complex with the identification of the first direct host partners. She continued to work on apicomplexan parasite, in Dr. Boris Striepen laboratory at the University of Pennsylvania, with a long-term postdoctoral EMBO fellowship. Her work focused on the investigation of Cryptosporidium, responsible for diarrheal disease, and how it manipulates the infected intestinal epithelial cell. She identified and characterized the first secreted effectors in Cryptosporidium confirming that the tools are now available to decipher this complex interaction at the molecular level3,4. She identified the entire secretome of the parasite using spatial proteome5. She also used live imaging techniques to decipher the parasite invasion process as well as the parasite lifecycle highlighting unique mechanisms6,7. In addition, in collaboration with Dr. Chang laboratory, she used cryo-electron tomography to elucidate the machinery of a specialized secretory organelle, the rhoptry, in Toxoplasma, Plasmodium and Cryptosporidium8-10. This technique allowed the 3-dimensional reconstruction of the rhoptry secretion apparatus and provide the first structural framework for understanding the secretion mechanism. In April 2023, thanks to the support of a PRIMA SNSF grant, she opened her laboratory at the University of Geneva, in the department of Microbiology and Molecular Medicine, where she focuses on the characterization of Cryptosporidium secreted effectors and their impact on the infected host cell.
https://www.unige.ch/medecine/mimo/en/groupes/amandine-guerin/
17 Aug 2023