Two research projects from NARILIS selected for funding under the WELBIO Investigator Programme

Funded by the Walloon region, the WELBIO (Walloon Excellence in Life Sciences and Biotechnology) programme is aimed at supporting strategic research in life sciences, with a view to translate discoveries into industrial applications.

The outcome of the last call for proposals of the WELBIO Investigator Programme, launched in September 2023 by the FNRS, has just been announced. Among the 21 newly selected research projects, two are led by researchers from NARILIS.

Prof. Alison Forrester is appointed WELBIO investigator with her project “Identification of compounds that target ERES and anterograde trafficking, and their application in disease models of aberrant secretion”.

Approximately one-third of proteins are synthesized in the endoplasmic reticulum (ER), where they undergo modifications, folding, and subsequent trafficking through the secretory pathway. Alison Forrester’s research focuses on the ER exit sites, which are specialized areas of the ER dedicated to the formation of COPII coated carriers, cargo loading and transport to the Golgi. ER exit is a tightly controlled process, and its deregulation can cause catastrophic aberrations in protein secretion, potentially leading to severe diseases, such as fibrosis and neurological disorders.

The potential of targeting ERES as a therapeutic strategy was recently validated by the discovery of Retro-2, the first specific pharmacological inhibitor of ERES. The WELBIO project led by Alison Forrester now seeks to identify additional compounds capable of modulating ER-Golgi trafficking of secreted proteins. Her group will then identify which diseases could benefit therapeutically from treatment with these compounds and test the new ERES modulators in relevant disease models. This work will pave the way for novel treatment approaches to treat the very common, and still untreatable diseases of aberrant secretion.

Prof. Xavier De Bolle becomes a WELBIO investigator with his project “Lipopolysaccharide O-chain biosynthesis in Brucella abortus: from fundamental knowledge to synthetic microbiology”.

Brucella is the bacterial pathogen responsible for a major worldwide zoonosis called brucellosis, which causes abortion in domestic animals and undulant fever in humans. Xavier De Bolle's team aims to elucidate essential processes in the molecular biology of Brucella abortus, particularly its adaptation to various stresses during its infectious cycle and its growth within hosts. Over the past 20 years, the team has made important discoveries about bacterial cell cycle, stress response mechanisms as well as envelope biosynthesis and regulation during growth.

As part of the WELBIO project, they will continue investigating lipopolysaccharide (LPS) biosynthesis, a main component of the envelope outer membrane. The team previously discovered that Brucella abortus displays unipolar growth, with LPS being incorporated at the active growth sites, and proposed a model for LPS transport across the cell envelope from the inner to the outer membrane. Smooth LPS containing a O-chain is required for Brucella abortus virulence.  The new WELBIO project aims to characterize the O-chain biosynthesis pathway and the translocation system responsible for exporting smooth LPS to the outer membrane. This deeper understanding of LPS biosynthesis and export will allow the production of smooth LPS from pathogenic Brucella strains in harmless bacterial strains, opening possibilities for further research and applications.