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Professor Barbara Costa; Professor Ayikoé, Guy Mensah-Nyagan.
PhD project Title (Joint supervision of Doctoral thesis)
Neuroprotection against abnormal myelination and neuroinflammation: role of TSPO-mediated regulations and genome editing based strategies against PLP mutation-induced oligodendrocyte death.
My PhD research project, to be developed in collaboration with the INSERM Unit 1119 – Biopathology of Myelin, Neuroprotection & Therapeutic strategies (University of Strasbourg), has the purpose of investigating the mechanisms involved in abnormal myelination and neuroinflammation underlying neurodegenerative and/or neurological disorders. In particular, the project will focus on the two following targets:
(i) the mitochondrial Translocator Protein 18 kDa (TSPO);
(ii) the major myelin Proteolipid Protein (PLP).
During the first year of activity, I focused my research on the functional role of TSPO in immunomodulatory processes. Our published results are in favor of a homeostatic role for TSPO in the context of dynamic balance between anti-inflammatory and proinflammatory mediators in the human microglia-mediated inflammatory response. Our hypothesis is related to the steroidogenic activity of TSPO, and our future aim is to evaluate the effective steroids production by microglia cells. Besides, the study the regulation of TSPO gene transcription in inflamed glia cells will be performed, since its expression increases during the inflammation and returns to basal level when the phenomenon is resolved.
Over the course of the 18 months at University of Strasbourg, I will be mainly focused on the modulations of PLP mutation and TSPO activity in oligodendrocytic and cell model of myelin disorders. Mutations of the major myelin protein PLP causes oligodendrocytes (OL) death, myelin abnormalities and neuronal dysfunctions leading to neurological disorders. First, we will study the effects of genome editing based strategies (CRISPR/Cas9) against PLP-mutation-induced OL death. Then, the modulation of TSPO neurosteroidogenic activity to counteract PLP-mutation-evoked OL death will be experimented. To determine TSPO-mediated actions, particularly the role of TSPO-induced neurosteroidogenesis in the control of OL activity and myelin formation, the project will investigate the effects of potent residence time-based selected TSPO ligands on OL life/survival, differentiation and myelinating activity.
Oral communications at congress:
Tremolanti C., Da Pozzo E., Giacomelli C., Costa B., Martini C. TSPO e regolazione dei processi neuroinfiammatori. Di nuovo TUM: Mappatura interregionale delle tematiche SIB tra Toscana, Umbria e Marche. 2019, June 11, Ancona, Italy.
Tremolanti C., Da Pozzo E., Giacomelli C., Martini C., Costa B. Translocator Protein (TSPO, 18 kDa) in neuroinflammation: investigation of its functional role in primary human microglia. XIX Congresso Nazionale AIBG – Associazione Italiana di Biologia e Genetica Generale e Molecolare. 2019, October 4-5, Milano, Italy.
Poster communications at congress:
Tremolanti C., Giacomelli C., Cavallini C., Martini C., Da Pozzo E. Sex differences in hypertension: in vitro studies. International Meeting Steroids and Nervous System. 2019, February 16-20, Torino, Italy.