Six ULiège projects selected for Welbio Investigator Program funding
The results of the FNRS Welbio FRFS call are in! Among the 23 new research projects in Life Sciences selected, five are led by researchers from the GIGA er interdisciplinary research unit of the FARAH of the University of Liege. Welbio grants more than 13 million € for 23 new research projects in Life Sciences.
Becoming cancerous: the role of tRNA players in the establishment of cancer stem cells | Starting Grant
Cancer stem cells (CSCs) - a small population of transformed cells - are cells that are capable of sustaining tumour growth and are responsible for the development of metastasis and drug resistance in patients. The incredible plasticity and genetic heterogeneity of CSCs make it extremely difficult to find global markers and/or molecular fingerprints uniquely expressed by these cells. The project's objective led by Francesca Rapino - FNRS researcher at the GIGA - is to approach the concept of CSCs from a new and highly innovative perspective: to describe the cell site of origin of CSCs as a population harbouring a tRNA signature that is permissive to tumour transformation. The specific signature of tRNA molecules would allow the establishment of onco-proteomes supporting the transformation of cancer stem cells. Therefore, identifying this permissive signature could be predictive of the population of origin of these CSCs.
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Using herpesvirus-fish models to study host-pathogen-environment interactions: a new approach to disease control in aquaculture | Advanced Grant
Several observations have demonstrated the role of the environment in developing certain infectious diseases. This has led to the concept of the "host-pathogen-environment" triad. Prominent examples of this concept are the effect of water temperature on the development of viral diseases in fish or the effect described in mammals of the microbiome on "trained immunity". The project led by Alain Vanderplasschen, director of the immunology and vaccinology laboratory, aims to study three original and fundamental hypotheses concerning host-pathogen-environment interactions and is based on three herpesvirus/fish homologous models developed in his laboratory. These three fundamental hypotheses, which will focus on host immune responses to a pathogen, are all centred on understanding the effect of the environment on host-pathogen interactions, particularly its immediate impact on disease development and its longer-term impact on the host and the virus. Two of the three hypotheses on which the researchers will work are aimed at developing technological innovations for disease control in aquaculture.
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Cell migration shapes cerebral cortex morphogenesis and function | Advanced Grant
Most cells in the mature cortex are born at a distance during embryogenesis. Cell migration is, therefore, a key process that brings neural cells to their final position in the cortex. Recent work, notably in the GIGA Stem Cells Laboratory led by Laurent Nguyen, FNRS research director, suggests that cell migration may also convey instructive signals to neighbouring structures/cells, thus shaping cortical morphogenesis. In this project, the researchers will combine the analysis of transgenic mice with that of human organoids/assembloids to better understand the transient role of two cell populations that actively migrate into the developing cortex from the ventral forebrain: interneurons (cIN) and oligodendrocyte progenitor cells (vOPC). In developing this project, the researchers hope to answer two questions: Does the timing of cortical invasion by cINs influence the establishment of neuronal networks in the cerebral cortex? What is the role of vOPCs that migrate tangentially during the cerebral cortex development?
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Laurent Nguyen
Identification of IBD susceptibility genes and interacting drugs by systematic eQTL and CMap analysis | Advanced Grant
Chronic Inflammatory Bowel Diseases (IBD) are a growing public health problem that threatens the sustainability of our health care system and requires novel preventive and therapeutic approaches. Genome-wide association studies (GWAS) have identified more than 220 loci (fixed position of a genetic marker on a chromosome) affecting susceptibility to IBD through quantitative trait loci affecting gene expression (eQTL), the majority of which are not yet identified. The project led by Michaele Georges, Director of the GIGA, aims to generate a novel unique dataset for the identification to identify eQTLs in 70 IBD-relevant immune and intestinal cell types relevant to IBD and using bulk and single-cell RNA-sequencing, resting and activated cells, from healthy and diseased patients, fo a total of > 10.000 transcriptomes. The project also aims to identify small molecules and drugs that may interact with the candidate genes. eQTLs and thus genes involved in IBD susceptibility. The aim is the identification of candidate drugs for the treatment and prevention of IBD, including opportunities for repurposing.
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Michel Georges
Deciphering the contribution of the myeloid-epithelial axis to exacerbations of chronic lung disease: a key route to precision medicine and improved quality of life | Advanced Grant
Acute exacerbations of chronic respiratory diseases such as asthma or chronic obstructive pulmonary disease (COPD) are a significant burden on health systems. Respiratory viral infections frequently trigger them, are not well controlled by current therapies and have severe consequences for patients. Therefore, understanding the mechanisms underlying exacerbations (so-called VirAttacks) is an urgent need to identify new biomarkers and therapeutic targets. The DECODE VirAttacks project, led by Thomas Marichal, FNRS researcher at the GIGA, is based on the premise that virus-infected epithelial cells (ECs) interact in asthma and COPD patients closely with distinct subpopulations of myeloid cells to shape their identity and orchestrate the pathological characteristics of VirAttacks. This project is an ambitious and innovative translational research programme to study the bidirectional communication between ECs and myeloid cells during VirAttacks deeply. The researchers hope to reveal new key cellular and molecular mechanisms of VirAttacks in asthma and COPD to identify new biomarkers of disease risk and severity and contribute to the development of new approaches to personalised medicine.
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Thomas Marichal
Epitranscriptomics of transfer RNAs: a new vulnerability in cancer | Advanced Grant
Regulation of mRNA translation represents a central mechanism supporting cancer cell adaptation during tumour progression and therapeutic response. Many oncogenes converge to translation regulation and aberrant activity of the translational machinery, correlated with increased protein synthesis, is a hallmark of malignant cancer cells. Research in the laboratory of Pierre Close, Senior FNRS researcher at GIGA Stem Cells, indicates that the wobble uridine tRNA modification pathway is commonly overexpressed in cancers and plays a crucial role in the establishment and maintenance of cancer phenotypes by regulating the synthesis of specific proteins. These findings have revealed the underestimated importance of tRNAs in the expression and maintenance of the expression of proteins essential to sustain tumour development and therapeutic resistance. In this project, the researchers will study the importance of tRNA regulatory dynamics and modification in cancer development and regulation of tumour immunity by combining in vivo models, patient-derived material and unbiased approaches. Through this project, the researchers hope to discover new general mechanisms linking the regulation of tRNAs and their modification to cancer biology. This strategy will allow the discovery of new vulnerabilities in cancers that can be exploited to develop future anti-cancer treatments.
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Pierre Close
Welbio
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.
