{"id":"https://openalex.org/G84141011","display_name":"Regeneration by Chromatin-Remodeling Enzymes in Myelinating Glia","description":"Chromatin-remodeling enzymes are key transcriptional regulators that control cell differentiation during development. By post-translational modifications of histones, these enzymes locally modify chromatin compaction and thereby control the accessibility of target genes for the transcriptional machinery. Histone deacetylases (HDACs) are very potent transcriptional regulators. Indeed, these enzymes control transcriptional activity at the chromatin level, and also by deacetylating transcription factors to modulate their activity. There are 18 known mammalian HDACs subdivided into 4 classes based on their structure. We have recently shown that the two highly homologous class I HDACs HDAC1 and HDAC2 are critical for the specification of neural crest cells into Schwann cell precursors, which further differentiate to become the myelinating glia of the peripheral nervous system (PNS). In addition, my previous work showed that HDAC1 and HDAC2 are essential at a later developmental stage for the transcriptional program of myelination and the survival of Schwann cells. HDACs have also important functions in the development of oligodendrocytes, the myelinating glia of the central nervous system (CNS).I hypothesized that chromatin-remodeling enzymes are also critical for regeneration and maintenance of integrity of the PNS and CNS. Great discrepancies exist between the plasticity of the PNS and CNS. Indeed, in case of a lesion, peripheral nerves can spontaneously and fully regenerate, whereas regeneration of the CNS after lesion is mostly inefficient. This is mainly due to the different types of glial cells present in these two systems. In case of a PNS lesion, Schwann cells located distal to the lesion site dedifferentiate to return to an immature stage, where they reproliferate and migrate along damaged axons to give them guidance for regrowth. Once axons have regrown, Schwann cells redifferentiate to remyelinate axons. In contrast, oligodendrocytes do not have the ability to dedifferentiate after a lesion and their myelin proteins inhibit axonal regrowth. Thus, damaged axons cannot regenerate. Understanding the mechanisms that control Schwann cell dedifferentiation and redifferentiation after lesion is thus crucial for the use of Schwann cell regenerative properties to design new treatments for degenerative diseases of the PNS. Preventing degeneration is a complementary approach to regeneration and is also critical to maintain the integrity of the nervous system in the case of neurodegenerative diseases. In addition, and of major importance, this new knowledge will potentially lead to novel strategies for the repair of CNS lesions caused by accidents or degenerative diseases, and for the maintenance of CNS integrity to prevent degeneration.      During the first three years of my SNSF Professorship, we have focused our studies on the potential functions of HDACs in myelinating cells during the regeneration process of the PNS and CNS, and in the maintenance of their integrity, as planned in my first proposal.The present project consists of the two following complementary aims: 1/ Deepen our understanding of HDAC functions in myelinating glia during regeneration and maintenance of integrity, based on our new findings during the first part of my SNSF Professorship, 2/ Increase oligodendrocyte plasticity after lesion.To reach the first aim of this project, we will continue to analyze HDAC functions in myelinating cells and their mechanisms of action during regeneration and maintenance of the nervous system. To reach the second aim, we will modulate HDAC expression and/or activity to increase oligodendrocyte plasticity after axonal lesion in vitro. We will then test the most promising strategies of exploratory treatments in adult mice to reprogram oligodendrocytes after a spinal cord lesion.To conduct these studies, we will use cutting-edge technologies, including temporally controlled cell type-specific gene ablation in mice, in vivo injection of viral vectors, local delivery of DNA in the spinal cord, transcriptomics and epigenomics analyses. This project is at the forefront of research on chromatin-remodeling enzyme functions in the nervous system and will advance mechanistic understanding of nerve repair; furthermore, it holds the exciting potential to identify novel therapeutic strategies for regeneration of the PNS and CNS after a lesion caused by diseases or accidents.","funder_award_id":"163759","funder":{"id":"https://openalex.org/F4320320924","display_name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi":"10.13039/501100001711"},"funded_outputs":["https://openalex.org/W2583414060","https://openalex.org/W2751464383","https://openalex.org/W2952946123","https://openalex.org/W3041029720","https://openalex.org/W4406162414"],"funded_outputs_count":5,"parent_awards":[],"sub_awards":[],"sub_awards_count":0,"amount":399089.0,"currency":"CHF","amount_usd":399529.98,"amount_usd_basis":"daily_rate","recipients":[{"id":"https://openalex.org/I154338468","display_name":"University of Fribourg","ror":"https://ror.org/022fs9h90","country_code":"CH","roles":["lead"],"share":null,"basis":"affiliation_matcher","asserted_by":"funder"}],"recipient_countries":[{"country_code":"CH","share":1.0,"amount_usd":399529.98,"basis":"organisation_location"}],"recipient_regions":[],"research_scope":{"is_research":true,"basis":"funder_default","tier":1},"funding_type":"fellowship","funder_scheme":"SNSF Professorships","start_date":"2016-03-01","end_date":"2017-02-28","start_year":2016,"end_year":2017,"landing_page_url":"https://data.snf.ch/grants/grant/163759","doi":null,"provenance":"snsf","lead_investigator":{"given_name":"Jacob,","family_name":"Claire","orcid":null,"role_start":null,"affiliation":{"name":"University of Fribourg \u2013 FR","country":"Switzerland","ids":null},"author":{"id":"https://openalex.org/A5053209401","display_name":"Claire Jacob","orcid":"https://orcid.org/0000-0001-9567-3950"},"institutions":[{"id":"https://openalex.org/I154338468","display_name":"University of Fribourg","ror":"https://ror.org/022fs9h90","country_code":"CH","type":"education","lineage":["https://openalex.org/I154338468"]}]},"co_lead_investigator":null,"investigators":null,"works_api_url":"https://api.openalex.org/works?filter=awards.id:G84141011","primary_topic":{"id":"https://openalex.org/T11736","display_name":"Histone Deacetylase Inhibitors Research","score":0.5466,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T11736","display_name":"Histone Deacetylase Inhibitors Research","score":0.5466,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"institution_awarded":[{"id":"https://openalex.org/I154338468","display_name":"University of Fribourg","ror":"https://ror.org/022fs9h90","country_code":"CH","type":"education","lineage":["https://openalex.org/I154338468"]}],"updated_date":"2026-11-11T03:01:08.000Z","created_date":"2026-07-13T04:27:35.000Z"}