The central nervous system is composed principally of neurons and three different types of glial cells (astrocytes, oligodendrocytes and microglial cells). With age, there is a progressive loss of structure and function of neurons, as well as a loss of damaged and dysfunctional neurons. Progressive degeneration and/or death of neurons drives neurodegenerative disease.
Two areas of the adult brain generate new neurons and glia from neural stem cells and progenitor cells: (i) the subgranular zone of the hippocampus, and (ii) and the subventricular zone lining the lateral ventricle. With age, adult neurogenesis decreases.
Regulation of thyroid hormone availability has been implicated in the complicated multi-step processes of (i) adult neurogenesis, and (ii) differentiation/maturation of oligodendrocyte precursor cells. Owing to the links between TH signalling and neurodegenerative diseases associated with ageing, one of our main hypotheses is that inappropriate thyroid hormone action in neural stem cells/progenitor cells underlies susceptibility to age-related neurodegenerative diseases.
Our team is investigating how thyroid hormone signalling is regulated in the neural stem cells/progenitor cells, and how it affects neural stem cells biology during ageing.
Financed as part of the THYRAGE European project, the candidate will carry out work within this project, notably determining how local regulation of thyroid hormone action controls adult neurogenesis. Part of the work will use mouse models. To this end, the candidate will test the effects of thyroid hormone signalling manipulation (cell specific knockout of deiodinases and thyroid hormone transporters) on NSCs renewal, proliferation and differentiation by analysing protein levels and gene expression of specific target.
Prof. Barbara Demeneix
Dr. Sylvie Remaud
Application deadline: 08/01/2018
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The post-doctoral fellow will join the research team “Integration of transcriptional responses inducted by thyroid hormones and their receptors” (Prof. Demeneix)