
Stephane Belin
- [GIN] Grenoble Institut des Neurosciences (GIN)
Présentation
Over the last 6 years, I set-up my independent lab on the molecular mechanisms of axon regeneration in the central nervous system. Since then, I published 10 scientific articles/reviews in peer reviewed journal. Several publications have been accepted in the most prominent journal in the field of neuroscience (Neuron) and general audience journals (Nature Communication, PLoS Biology, Science). Those listed below demonstrated my impact in the field of axon regeneration and protein translation. Since my establishment as independent researcher, I demonstrated my ability to secure grants (competitive national Grant form ANR, UNADEV…) and successfully drive project leading to major breakthroughs and publications. I have also set-up key and fruitful collaboration to develop project around mass spectrometry, RNAseq analysis, neuronal recording/stimulation and ribosome structure as represented by the number of common publications with collaborators. During my PhD with Dr Jean-Jacques Diaz, I identified modifications of the ribosome induced by different physio-pathological stresses such as virus infection (Belin et al., RNA, 2010), cancer progression (Belin* et al., Plos One, 2009a and b) and cancer development (Marcel* et al., Cancer Cell, 2013). My work has profound implication in the reinterpretation of the role of the ribosome and the translational complex in the regulation of translation. Indeed, my work has shed light on the existence of different pools of ribosomes and the direct involvement of ribosome composition in translation regulation of specific mRNA. This led to the emergence of several studies on rRNA chemical modifications role on translation. I then pursued my career as a postdoc in the laboratories of Pr Zhigang He and Dr Judith Steen (Harvard Children Hospital). I extended my analysis of translation control during stress by investigating the injury response of central nervous system (CNS) neurons to injury. I developed a quantitative based proteomics approach of pure neuron population. Based on this analysis, I demonstrated that c-myc is essential for neuronal survival and can induce strong CNS axon regeneration when expressed before or after injury. In addition this protein synergizes with mTOR and JAK/STAT pathways to induce strong regeneration close to the original targets (Belin* et al., Neuron, 2015). Second, I demonstrated that DCLK2 is essential for neuron survival by controlling axonal transport and for axonal regeneration by promoting growth cone formation after injury by the stabilization of microtubules and actin (Nawabi* et al., Neuron, 2015a). Finally I highlighted the crucial role of translation regulation during injury (Belin* et al., Neuron, 2015b). I established an independent laboratory in the Grenoble Institute of Neuroscience (France) in 2018 in order to analyze the exact composition of the translational complex (ribosome, translation and associated factors) and define its implication into the control of protein synthesis and its role for neuroprotection and regeneration in adult nervous system. I have developed a new ex-vivo model of axon regeneration and injury that reproduces all the features of the in-vivo model. This powerful system is perfect to analyze molecular events at a single axon resolution and is particularly pertinent for local translation analysis (Schaeffer et al, Frontiers in Mol Neuro, 2021). I participated to the characterization of axon guidance modalities in adult during regeneration. Using proteomic analysis, we defined a comprehensive map of guidance cue in the visual system (Vilallongue et al., Nat Communication 2022). I also determined that ribosomal proteins composition can differ according mice organs (Brunchauld et al in preparation). My analysis of the translational complex also reveals HTT as a new ribosome interactant, controlling specifically mRNA translation important for CNS axon regeneration (Schaeffer et al, Neuron 2023). Finally, I characterized the central role of RSK pathway and the phosphorylation of ribosomal protein in both peripheral (PNS) and central (CNS) nervous system regeneration (Decourt et al, PLoS Biology 2023). My work has shed light on key molecular mechanisms necessary to promote axon regeneration and circuit formation in adults and reinforces the notion of specialized ribosome.