WELBIO is an inter-university life sciences research institute based in Wallonia, Belgium. WELBIO aims at promoting scientific excellence in fundamental life sciences research and translating scientific achievements in medical, pharmaceutical and veterinary biotechnology applications.
Lung regulatory macrophages: phenotype, function and therapeutic potential
In 2009, the laboratory of Cellular and Molecular Immunology (Fabrice Bureau) identified lung interstitial macrophages (IMs) as important regulators of pulmonary immune homeostasis. Indeed, in mice, they showed that IMs may counteract the development of adaptive immune responses toward inhaled allergens. More recently, they have uncovered an as-yet unappreciated role for IMs in mediating the well-known immunotherapeutic effects of bacterial CpG-DNA. They have indeed shown that CpG-DNA has the unique ability to substantially expand IMs from monocytes and to provide them with a hypersuppressive profile. In this WELBIO project, Fabrice Bureau ans his team propose to investigate in-depth the phenotypic and functional plasticity of IMs at steady-state and during inflammation. This will enable them to better understand an essential regulatory mechanism by which health and homeostasis are maintained in the lung mucosae. Moreover, this could help in developing new therapeutic strategies for the treatment of chronic airway inflammatory diseases.
> Continuation grant (2017-2021)
tRNA modifying enzymes and their targets in immunity and cancer
This project focuses on protein reprogramming (the modification of the "program" for translating messenger RNAs into proteins) that is involved in the immune response and in cancer. Changes in chemical modifications of transfer RNAs (tRNAs) play an essential role in this reprogramming. With his group, Alain Chariot described the role of an enzyme that modifies tRNAs, the Elongator protein complex, in several cancer models. He is now studying proteins whose translation depends on Elongator. This project aims to understand the role of these enzymes in several oncogenic pathways. Another aspect of the project will address the role of tRNA modifications in the immune response. The mechanisms by which Elongator promotes the differentiation of intestinal Tuft cells will be studied. These cells are involved in the immune response to a parasite infection in the intestine.
> Continuation grant (2019-2021)
Translation reprogramming through wobble tRNA modification in cancer
Large scale sequencing of human tumours led to the identification of cancer driver genes that confer selective advantage to cancer cells and stimulated the development of specific therapies that improved the overall prognosis of cancer patients. The heterogeneity in tumour genetic alteration is contrasted by an apparent convergent evolution of cancers, where a limited number of molecular strategies are developed by cancer cells to survive hostile environment or therapeutic interventions. A number of genes and associated functions that are not inherently tumorigenic and frequently involve stress response pathways appear to be essential for the acquisition of tumour traits. Our project will uncover strategies developed by cancer cells to escape therapeutic control. We envision that cancer cell adaptation relies on fundamental, highly conserved, mechanisms that affect specific protein synthesis and have been developed by early organisms. Theproject of Pierre Close and his team aims at understanding protein synthesis rewiring in tumour development and resistance to therapy. This project will uncover new opportunities to interfere with cancer cells adaptation and to improve the therapeutic response of cancer patients.
> Starting grant (2017-2021)
Epithelial cells as master regulators of mucosal homeostasis: unraveling the regulatory role of Rab guanine nucleotide exchange factor-1 (RABGEF1)
Epithelial barriers constitute the physical interface between the host and the environment, and are increasingly recognized as critical regulators of immune homeostasis. The goal of this project is to understand how the dysregulation of epithelial cell (EC) functions, by altering interactions between the environment and the host, can contribute to the pathogenesis of mucosal diseases such as inflammatory bowel disease (IBD) or asthma. The team of Thomas Marichal have demonstrated that the guanine exchange factor protein RABGEF1, was a regulator of epidermal keratinocyte-intrinsic signaling that maintained skin homeostasis and prevented development of atopic dermatitis. In this project, they will investigate the role of EC-intrinsic RABGEF1 in mucosal homeostasis and host-microbial interactions, using mouse models and relevant human materials. The molecular mechanisms by which RABGEF1 maintains epithelial homeostasis will also be studied. This project is expected to reveal new insights into barrier and immune functions of EC that are fundamental for maintaining mucosal homeostasis and preventing immune-mediated diseases.
> Starting grant (2017-2021)
Lymphendo : Innovative roles of uPARAP in lymphatic vessel morphogenesis and functions
> Advanced Grant ( 2019-2021)