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IPPreport

Development of a first cellular reporter for monitoring inositol pyrophosphate messengers
Funder: French National Research Agency (ANR)Project code: ANR-24-CE44-1619
Funder Contribution: 285,232 EUR

IPPreport

Description

Inositol pyrophosphates (IPP) have been recently characterized as important signaling molecules in organisms ranging from plants, slime moulds and fungi to mammals. Extensive research has been conducted on the IPP pathway revealing the role of these molecules on organogenesis, diseases (e.g., cancer metastasis and deafness), nutrient homeostasis, and plant hormone responses. IPPs are present in cells as multiple isomers at low concentrations, subject to rapid interconversion, making them a real challenge to monitor in vivo, and restricting our ability to define the specific roles of different IPP molecules. To solve this problem, and further determine the subcellular and tissular distribution of IPP molecules, we have initiated the design of a cellular reporter for monitoring IPPs in real-time. The reporter combines the cellular IPP receptor, formed by a SPX dimer, with the recently established split FAST system. Preliminary work in yeast showed that the first version of the reporter produces a black-and-white fluorescence change when responding to cellular IPP accumulations. We propose here to characterize the kinetics and dynamics of the IPP reporter in yeast cells and improve its selectivity to sense different IPP species and isomers. We further plan to transfer the IPP sensor to plants to address the fundamental characteristics of IPP signaling in a multicellular organism. We believe that the IPP reporter could be transferred in the future to cancer cell lines for a better understanding of IPP-regulated cancer metastasis.

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