Research

Three ULiège projects selected for Welbio Investigator Program funding

WEL Research Institute


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As part of the Welbio Investigator Program call for projects, two FARAH projects and one GIGA project have been selected for funding at the Université de Liège.

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hrough this funding, Wallonia grants significant resources over several years to WELBIO Investigators within the WEL Research Institute, enabling them to develop ambitious research programs and achieve new scientific breakthroughs. WEL Research Institute Investigators must demonstrate their scientific excellence, their knowledge of the medical and technological needs in their field, and their willingness to look for opportunities to apply their discoveries

As part of the 2023 call, 3 projects have been selected at ULiège :

Pneumovirus infections lead to lasting alterations in host immunity, promoting the development of lung cancer | Starting Grant

CONTACT Bénédicte Machiels,Faculty of Veterinary Medicine, FARAH - Veterinary Public Health, Department of Infectious and Parasitic Diseases (DMI )

Environmental factors influence the development of diseases, including cancers. Respiratory viruses are highly prevalent and potentially responsible for lasting alterations in host immunity. However, the impact of these changes on anti-tumor immunity is poorly studied. The human respiratory syncytial virus (RSV), a pneumovirus responsible for bronchiolitis in children and recurrent infections in the elderly, is intriguing. Although causing transient infection, this virus is associated with the development of type 2 immunopathologies later in life, suggesting long-term immune imprinting. The aim of this project is to investigate whether and how pneumovirus-induced immune imprinting can affect anti-tumor immunity. To this end, we will use the mouse pneumonia virus (MPV), homologous to RSV, and several tumor models (Lewis lung carcinoma cells as well as a model of spontaneous lung tumor development). First, we will test these models in mice to characterize clinically and histologically the impact of PVM pre-infection on anti-tumor immunity. We will then use flow cytometry, scRNA seq, imaging and spatial mapping to define the cellular and molecular changes associated with PVM following tumor implantation. We will also study the underlying mechanisms using in vivo approaches such as conditional KO mice, depletion, adoptive transfer and epigenetic analysis of myeloid progenitors. Finally, strategies to prevent or correct the deleterious imprinting caused by PVM will be tested in preclinical models. This research could reveal the immunomodulatory effects of pneumoviruses in promoting cancer development, and identify innovative prophylactic/therapeutic targets.

 

Translational reprogramming through tRNA modifications in health and diseases | Advanced Grant

CONTACT Alain Chariot,Faculté de Médecine ,GIGAStem Cells - Medical Chemistry

Protein reprogramming enables cancer cells to proliferate and survive longer. Many human pathologies are characterized by deregulation of this reprogramming. Chemical modifications of transfer RNAs regulate the translation of messenger RNAs and therefore play an important role in protein reprogramming. The Elp3 enzyme modifies certain transfer RNAs and is involved in tumor development and metastatic progression. Loss of Elp3 function in hepatocytes leads to post-natal mortality via a blockade of glucose production. We will define the mechanisms by which Elp3 promotes cell differentiation in the liver. We will identify new targets whose translation involves Elp3. Loss of Elp3 function in adipocytes exacerbates weight gain following a high-fat diet. We will identify the molecular players involved in adipocyte hypertrophy whose translation is regulated by Elp3. Finally, we will determine whether loss of Elp3 function in adipocytes sensitizes mice to obesity-related liver cancer. Finally, we will also explore the role of Lepre-1, a hydroxylase that targets proline residues, in tumor development in the intestine. Our work will provide new insights into how chemical modifications of transfer RNAs regulate hepatocyte and adipocyte biology, with important consequences for hepatic metabolism, obesity and obesity-related liver cancer. Our project will also provide a signature of Lepre-1-hydroxylated prolines during tumor development.

 

Deciphering the mechanisms regulating the effector functions of virtual memory T lymphocytes during helminth and viral coinfections | Advanced Grant

CONTACT Benjamin G. DEWALS,FARAH: Veterinary Public Health, Department of Infectious and Parasitic Diseases (DMI)

Certain CD8+ T lymphocytes, defined as 'virtual memory' Tvm cells, develop rapidly after stimulation by interleukin (IL)-4, a type 2 cytokine involved in helminthic immunity and allergic response. Although type 2 cytokines generally inhibit the type 1 immunity associated with antiviral immunity, IL-4-stimulated Tvm retain a type I IFN signature and produce antiviral effector molecules. The synergistic activity of type 1 and 2 immunity in Tvm cell function represents a paradigm shift in our understanding of host defense, offering an opportunity to dissect how disparate immune pathways converge to epigenetically form protective immunity. Understanding the mechanisms that control Tvm cell function is paramount to improving rapid protection against various pathogens. However, a number of questions remain unanswered: For example, how are Tvm cells uniquely imprinted with IL-4, and how long does this imprint last? How are autoreactive Tvm cells regulated? Can we exploit Tvm responses in species other than mice, such as humans or other animal species of veterinary importance? To fill these gaps, there is an urgent need to combine preclinical animal models of infection with bioinformatics approaches to reveal the complex molecular networks underlying Tvm cell function. Here, we will pursue three main objectives to identify fundamental mechanisms regulating Tvm cell responses that can be exploited for the next generation of interventions to manipulate T cell responses to infection.


About Welbio

The WEL Research Institute is an inter-university research institute based in Wallonia whose mission is to support strategic research of excellence. Its WELBIO department funds research programs in the life sciences, and promotes the valorization of scientific results into medical, pharmaceutical and veterinary biotechnological applications.

 

CONSULT WELBIO research projects at ULiège

Find out more about these projects and other research initiatives at ULiège

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