BESSE

Florence BESSE

Post-transcriptional control of neuronal plasticity

Main interests

  • understand how post-transcriptional regulatory processes control neuronal plasticity in vivo
  • study the regulatory mechanisms underlying neuronal RNP granule transport and dynamic properties
  • unravel the functions of mRNA transport and local translation in brain maturation and learning and memory processes
  • combine a variety of complementary approaches and perform multi-scale analyses

Scientific Questions

Our main research goal is to understand how post-transcriptional regulatory processes control neuronal plasticity in vivo. Specifically, we study how neuronal ribonucleoprotein (RNP) granules are regulated in space and time to promote local remodeling of neuronal cells during development, as well as in learning and memory processes. Neuronal RNP granules are dynamic macromolecular complexes that contain RNAs and regulatory proteins, assemble in the cell body, and are transported over long-distances to axons or dendrites. They are implicated in the transport of mRNAs, and in their local translation in response to external cues. Although alterations in the properties of neuronal RNP granules have been associated with different neurodegenerative diseases, surprisingly little is known about the molecular mechanisms underlying their formation and dynamics, as well as their physiological function and regulation.

Figure 1 – Neuronal RNP granules

Our Strategy

To understand the role of neuronal RNP granules in neuronal plasticity, as well as their spatio-temporal regulation in response to developmental signals or neuronal activity, one needs to i) dissect the molecular and cellular mechanisms underlying the assembly, transport and remodeling of these granules, and ii) test their functional impact during nervous system development or learning and memory processes. To address these questions, our lab performs multi-scale analyses, and uses Drosophila nervous system as an original in vivo system where advanced genetics, imaging and biochemistry can be combined. We use and develop a range of complementary assays including in vivo live-cell imaging, smFISH, in vivo RIP-seq, high throughput-microscopy, in vitro reconstitution assays. For some of our projects, we collaborate with computer scientists to perform automatic and quantitative image processing, and to develop mathematical models of the biological processes we study (See Morpheme Team ).

Figure 2 – GFP-Imp particle dynamic axonal transport

 

Research Aims

1- Neuronal RNP granules and axonal remodeling. We have shown that RNP granule components are actively recruited to axons undergoing remodeling in response to developmental cues. Furthermore, they are required for the regrowth of axonal processes that occurs after pruning of immature branches. Our objectives are i) to identify the mechanisms triggering RNP granule axonal recruitment and local translation of transported mRNAs, and ii) to understand their impact on axon regrowth and branching.

Figure 3 – 3D reconstruction of a single axon

2- Regulation of neuronal RNP granule assembly and dynamics. RNP granules are high order assemblages composed of RNAs and proteins dynamically exchanging with the cytoplasm. To identify regulators of the clustering and recycling of RNP granules, we are combining different approaches including biochemical purifications of RNP complexes, high throughput microscopy-based RNAi screens and in vitro reconstitution assays.

Figure 4 – Granules in cell culture

3- Regulation and function of neuronal RNP granules in synaptic plasticity and disease. We aim at understanding how neuronal RNP granules remodel in response to synaptic activity, and how this contributes to the structural changes underlying the establishment and retention of memories. As the progression of several neurodegenerative diseases has been linked to the formation of pathological RNP aggregates, we also study RNP granules assembled by RNA binding proteins involved in such diseases.

Figure 5 – Drosophila Mushroom Body

Researchers

DE GRAEVE Fabienne - +33 489150746
MEDIONI Caroline - +33 489150746

PreDocs

PUSHPALATHA Kavya Vinayan - +33 489150746
MORE Yogesh Walmikrao - +33 489150745
DE QUEIROZ Bruna - +33 489150746

Engineers & Technicians

PALIN Lucile - +33 489150746
BLOT Lauren - +33 489150746
SOLYGA Mathilde - +33 489150746
RAMEAU Marion - +33 489150866

 

Recent publications

Tyramine induces dynamic RNP granule remodeling and translation activation in the Drosophila brain Elife. 2021 Apr 23;10:e65742. doi: 10.7554/eLife.65742. Nadia ...
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Local Translation in Axons: When Membraneless RNP Granules Meet Membrane-Bound Organelles. Front Mol Biosci. 2019 Nov 22;6:129. doi: 10.3389/fmolb.2019.00129. eCollection ...
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Coopted temporal patterning governs cellular hierarchy, heterogeneity and metabolism in Drosophila neuroblast tumors. Elife. 2019 Sep 30;8. pii: e50375. doi: ...
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Detecting and quantifying stress granules in tissues of multicellular organisms with the Obj.MPP analysis tool. Traffic. 2019 Jul 17. doi: ...
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Neuronal RNP granules: dynamic sensors of localized signals Traffic. 2019 Jun 17. doi: 10.1111/tra.12672. [Epub ahead of print] Formicola N1, ...
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The prion-like domain of Drosophila Imp promotes axonal transport of RNP granules in vivo. Nat Commun. 2019 Jun 13;10(1):2593. doi: ...
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A stochastic framework to model axon interactions within growing neuronal populations. PLoS Comput Biol. 2018 Dec 3;14(12):e1006627. doi: 10.1371/journal.pcbi.1006627. eCollection ...
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Neuronal RNP granules: from physiological to pathological assemblies. Biol Chem. 2018 Jun 27;399(7):623-635. doi: 10.1515/hsz-2018-0141. De Graeve F1, Besse F1 ...
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TrawlerWeb: an online de novo motif discovery tool for next-generation sequencing datasets. BMC Genomics. 2018 Apr 5;19(1):238. Dang LT (1), ...
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Sumoylation regulates FMRP-mediated dendritic spine elimination and maturation Nat Commun. 2018 Feb 22;9(1):757. doi: 10.1038/s41467-018-03222-y. Khayachi A(1), Gwizdek C(1), Poupon ...
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2009 - HFSP Career Development Award

2008 - ATIP Biologie du Développement (CNRS)

2003 - HFSP, EMBO and FEBS Long-term Fellowships

iBV - Institut de Biologie Valrose

"Centre de Biochimie"

Université Nice Sophia Antipolis
Faculté des Sciences
Parc Valrose
06108 Nice cedex 2