Pedro Moura Alves
Since the start of my PhD, I have focused on understanding how bacterial infections are recognised by the host, with particular interest in innate immune recognition. Over the last few years, I have studied host-pathogen interactions, uncovering Pattern Recognition Receptors and signalling pathways triggered upon different bacterial infections, together with the identification of the pathogen counterparts participating in such crosstalk.
I recently discovered that the host encoded Aryl hydrocarbon Receptor (AhR) can be directly activated by bacterial molecules, including phenazines produced by the opportunistic pathogen Pseudomonas aeruginosa, as well as other molecules expressed during the course of bacterial infection. Pseudomonas aeruginosa phenazines are part of the Quorum Sensing system, a cell-to-cell communication system used by bacteria to coordinate their gene expression in response to changes in their population density, or infection stage. Therefore, if a host sensor can detect these different molecules and their expression patterns, it may allow hosts to customise their immune responses according to the stage of infection. Being capable of recognising a vast number of ligands and mounting fast transcriptional programmes in the host in response to infection, the AhR is well positioned to monitor bacterial infection dynamics and to rapidly shape immune responses accordingly. However, the elicited host responses might lead to fundamental changes in the bacterial community, whereby an adaptation to a new scenario might pose a new paradigm to the host that also needs to be evaluated.
In March 2019 I joined the Ludwig Institute for Cancer Research in Oxford as a Leadership Fellow to start my independent research group. My research focuses on understanding how the host innate immune system is capable of sensing changes in the microenvironment during the course of infection, both at cellular and organismal levels; and how upon sensing it orchestrates host defence mechanisms.
AhR sensing of bacterial pigments regulates antibacterial defence
Moura-Alves P. et al, (2014), Nature, 512, 387 - 392
Aryl Hydrocarbon Receptor Modulation by Tuberculosis Drugs Impairs Host Defense and Treatment Outcomes
Puyskens A. et al, (2019), Cell Host & Microbe
The insecticide chlorpyrifos modifies the expression of genes involved in the PXR and AhR pathways in the rainbow trout, Oncorhynchus mykiss
De Anna JS. et al, (2021), Pesticide Biochemistry and Physiology, 104920 - 104920
Cellular stress promotes NOD1/2‐dependent inflammation via the endogenous metabolite sphingosine‐1‐phosphate
Pei G. et al, (2021), The EMBO Journal
Novel Method for Quantifying AhR-Ligand Binding Affinities Using Microscale Thermophoresis
Stinn A. et al, (2021), Biosensors, 11, 60 - 60