Early Stage Researcher PhD fellowship in the Marie Skłodowska-Curie ITN European Training Network PANDORA on “Human macrophages as sentinels for discriminating normal innate response from anomalous reactivity to engineered nanoparticles”

The PANDORA network – Probing safety of nano-objects by defining immune responses of environmental organisms – aims at the education of promising young scientists who will learn shall assess the global impact of engineered nanoparticles (NP) on the immune responses of representative organisms covering all evolutionary stages and hierarchical levels from plants to invertebrates and vertebrates. PANDORA will train 11 PhD students in an overarching training programme involving training-by-research, joint courses of technical, scientific and transferrable skills, participation to public scientific events, and an intense intersectoral networking exchange plan. The PANDORA consortium encompasses academic institutions, research centers, and SMEs, all with proven experience in higher education and training, and state-of-the art scientific and technical expertise and infrastructures

The research activities implemented in PANDORA have the following objectives: 1. To identify immunological mechanisms triggered by nano-objects, and predictive markers of risk vs. safety; 2. To do so by a collaborative cross-species comparison, from plants to human, of innate immune defence capacity, using selected, industrially-relevant NP; 3. To design predictive in vitro assays to measure the immuno-risk of NP to the environment and human health, as new approaches to industrial and environmental nanosafety testing.
Each of the 11 ESRs will be enrolled in the PhD programme of the beneficiary’s organization (the beneficiaries which do not award PhD will establish agreements with local and international universities that can provide the degree) and will participate in the network’s training activities and work placements at the laboratories of the participating academic and industrial partners. In addition, the training programme of the recruited ESRs will be implemented with regular meetings and workshops within the PANDORA network.
The scientific project is based on human primary monocytes and monocyte-derived macrophages, which will be taken as model of vertebrate innate/inflammatory reaction upon exposure to nanoparticles. Macrophages are phagocytic and scavenging cells whose activity is conserved across species. Human tissue-like macrophages and blood monocytes will be used in in vitro models of resolving and chronic inflammation for representing the local tissue sentinels and the blood-derived inflammatory phagocytes, respectively. Cells will be challenged with foreign objects of different size, shape and stiffness (nanoparticles vs. bacteria or other materials) in order to understand the mechanisms underlying recognition vs. ignorance, activation vs. tolerance, selective activation pattern, and innate memory induction. Cells and supernatants will be sampled at several time points, to profiling gene expression (RNAseq and real-time PCR), rate of cytokine production (multiplex and single ELISA), lipid metabolism (mass spectrometry) and intracellular organelle trafficking (confocal, correlative microscopy, HC image acquisition). Expected results are: 1. understanding the mechanisms by which monocytes and macrophages recognise and react to foreign objects; 2. examining the possible interference of nanoparticles with the defensive functions of monocytes and macrophages; 3. assessing the capacity of nanoparticles to induce "innate memory" either in the direction of tolerance or in that of enhanced reactivity.