Understanding the impact of environmental POLlution on the adaptive Immune System

Introduction

There is growing evidence that currently used toxicological assessments of chemicals fail to fully capture their actual biological activity. While chemicals are routinely tested for acute toxic effects, often at high concentrations, potential function-modulating effects at low concentrations are often underexplored.

Importance of High-Resolution Methods

The inclusion of up-to-date high-resolution methods in the toxicological screening praxis would allow instead to fully capture the complex bioactivity profile of these compounds. This profile depends on numerous aspects including:

• Bioavailability
• Route of exposure
• Individual susceptibility

Historical Context

While the last 100 years have seen an enormous number of chemicals introduced into our daily life, a sufficient understanding of their bioactivity potential is lacking. A large number of these chemicals are well-known to persist in the environment.

Health Implications

Based on growing evidence, it is not far-fetched to hypothesize that some of these industrial chemicals could be partly responsible for the constant increase of non-communicable diseases. These include:

1. Autoimmune diseases
2. Chronic inflammatory diseases
3. Cancer
4. (Neuro)degenerative diseases

Focus on PFAS

Perfluoroalkyl and Polyfluoroalkyl Substances (PFAS) are a class of xenobiotics with proven strong toxicity at high-level exposure. However, little is known about their bioactivity at concentrations commonly detected in human samples.

Environmental and Health Concerns

Considering their high stability and ubiquitous occurrence in the environment and human body, exposure to PFAS has reached a pandemic scale.

Research Proposal

I postulate that it is of utmost importance to finally dissect the potential of these compounds to molecularly interfere with organ functionalities at the single-cell level using state-of-the-art high-resolution omics technologies.

Qualifications

Supported by an interdisciplinary training in pharmacology, systems immunology, omics, animal and cellular models, and bioinformatics, I represent a prime candidate to successfully develop this project and clarify the bioactivity of PFAS.