Single-cell imaging of host-parasite metabolic interactions in the liver (iMET)

Hepatocytes support the first massive amplification of malaria-causing Plasmodium parasites in the mammalian host. Despite clear parasitism and subversion of host cell resources, the molecular mechanisms implicated in favorable replication inside hepatocytes remain largely unknown. Metabolic signaling pathways appear to be modestly different in Plasmodium-infected hepatic cells compared to uninfected cells. However, these differences were measured by averaging cell populations and are likely masked by the high metabolic cell-to-cell heterogeneity recently unveiled in human and mouse hepatocytes. Also, in the previous studies it was not possible to discriminate whether the metabolic differences were a response to the parasite, or the parasite had selected to home in a hepatocyte where those conditions where already in place. To address the questions in the aim of the project, the researchers will employ the most-advanced single-cell live imaging approaches and bioengineered in vitro liver systems to probe the subpopulation of Plasmodium infected cells. Plasmodium liver-stage is the prime target for antimalarial therapeutic intervention, thus understanding the molecular basis and significance of hepatocyte homing signals and host-parasite metabolic interactions is fundamental in defining novel strategies.

Project details

Genetics and Genomics

Dec 2020 — Dec 2024

$433,616

France