ARC, two research projects selected at LIBST !

  • NanoViroStaph is a newly funded Concerted Research Actions (ARC) project led by A. Gillis (ELI), D. Alsteens (LIBST) and Y. Dufrêne (LIBST) that will start on October 2023. Bacteriophages have great therapeutic potential as an alternative to classical antimicrobials to fight pathogens such as multidrug resistant Staphylococcus aureus strains. Bacteriophages have been tested for clinical applications since the beginning of the twentieth century, yet the phage-bacterial-host interactions that lead to adhesion and invasion are still poorly understood. These are particularly critical when targeting bacterial intracellular pathogens, as they are protected from antibacterial agents and the host immune system, thus producing persistent infections. At the crossroads of nanotechnology and microbiology, this multidisciplinary research will combine state-of-the-art atomic force microscopy techniques with confocal microscopy and biological methods to broaden our understanding of the molecular interactions and mechanisms taking place in the phage-bacterium-host cell ternary system, using S. aureus and human skin cells as medically-important models. The project will have broad impacts as there is currently a strong demand for single live-cell nanotechniques in biology, and as resistant strains are becoming increasingly difficult to treat, meaning there is an urgent need for innovative virus-based antimicrobials.

 

  • EPISTEMODEVO, a Concerted Research Action (ARC) selected for funding, to be started in October 2023. This research project associates the teams of Charles Pence (Institut Supérieur de Philosophie), Frédéric Lemaigre (de Duve institute) and two teams from LIBST, those of Françoise Gofflot and René Rezsohazy.  Following the capacity to modify genes in animal genomes, developmental biology has flourished as a corpus predominantly aiming at understanding how genes and gene regulatory networks shape tissues, organs and the whole organism. A number of biologists and philosophers, however, have criticized the dominance of this gene-centric view of life which tends to overemphasize the search for and intervention on genes. In that context, the teams of F. Gofflot, F. Lemaigre and R. Rezsohazy so far investigated how gene regulatory proteins (namely transcription factors) that are integrated in gene regulatory networks control developmental processes. We now propose to approach such processes from another viewpoint and to address their epistemological implications.
    At the experimental level, we will characterize a neglected layer of molecular regulations taking place at the level of proteins, namely, protein stability, which is potentially a key determinant of developmental regulators' function. More specifically, we will focus on HOXA1, HOXA5, and HNF6. These three transcription factors share features that make them suitable for comparative studies: they are key regulators of cell fate determination and bind to target DNA via a conserved homeodomain. The role of the Hoxa1, Hoxa5 and Hnf6 genes have been well documented by inactivation or over-expression approaches. In contrast, the modes of action of the proteins they encode have been neglected. Therefore, we will characterize the longevity of these transcription factors, we will determine the protein domains, interactors and molecular pathways controlling their stability, and we will evaluate how modulating transcription factors stability impact developmental processes like heart development (HOXA1), hepatic cell differentiation (HNF6) and synaptogenesis in the brainstem (HOXA5).
    Further, together with the team of C.H. Pence, philosopher of biology, the epistemological dimension of our project will interrogate to what extent developmental biology has been gene-centric so far, and will appraise if leaving a gene-centric paradigm by addressing phenomena through the lens of regulations involving hypogenetic determinants defines a paradigm shift. We will also evaluate the importance of and changes in practices of model building and idealization in describing complex developmental processes.
    In our project, philosophers and biologists will work together in the labs to invest philosophy in practice and to question the way conclusions are drawn when proposing biological models and theories.

Published on March 21, 2023