MSCA4Ukraine. PIECE: Predicting the impact of exposome in human health by unbiased identification of chemical targets in cells

The purpose of this project is to develop methods for the unbiased identification of chemical targets in cells.

This project will focus on developing a new methodology for high-throughput identification of the membrane protein targets of chemical molecules.

The outcomes of this project would benefit the rapid discovery of mechanism of actions of novel drug and, the prediction of mechanism of action of emergent pollutants in human health.

Therefore, this proposal merges the candidate researcher interest as pharmacologist for the biodiscovery of pharmaceutical properties of novel compounds and the host lab vision of developing methodologies for the unbiased identification of targets from emergent pollutants that could predict their exposome impact in human health.The host lab has been the first to modify TPP and PISA for its application to identify targets of environmental chemicals, and has also modified PISA method for the identification of targets of environmental chemicals within the proteome from zebrafish embryo.There is an additional challenge before offering a complete map of chemical targets.

Membrane proteins interacting with environmental chemicals have been revealed as a common mechanism of toxicity for decades.

Therefore, the gap to fill is to develop a method that could maintain the solubilized membrane proteome stable across a needed range of temperatures and capture alteration of the target solubility only based on ligand binding effects.

The specific objectives of the projects are: i)establishing a methodology for proteome-wide identification of membrane protein targets from chemicals, and i) discovering new membrane protein targets for environmental chemicals. This methodology would facilitate chemical target identification with membrane protein in focus.

It will be applicable to toxicology but also drug target engagement, and discovery of mechanisms of actions from novel compounds from biodiscovery.