| Grant number: | 15/13345-1 |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| Start date: | December 01, 2015 |
| End date: | January 31, 2021 |
| Field of knowledge: | Biological Sciences - Biochemistry - Molecular Biology |
| Principal Investigator: | Alexander Henning Ulrich |
| Grantee: | Talita Glaser |
| Host Institution: | Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil |
| Associated research grant: | 18/07366-4 - Purine and kinin receptors as targets of study and therapeutic interventions in neurological diseases, AP.TEM |
| Associated scholarship(s): | 16/07659-6 - Huntingtin's Roles in Fate Decision of GABAergic Neurons Derived from iPSCs of HD Patients, BE.EP.PD |
Abstract Huntington's disease (HD) is a dominant inherited neurodegenerative disorder that is caused by mutation within the coding region of the huntingtin (HTT) gene, resulting in an elongated stretch of glutamine near the NH2 terminus of the protein. The consequence of HD mutation is a massive brain neurodegeneration characterized by the loss of GABAergic neurons from the basal ganglia. To fulfill the urge of developing treatments for HD, we need to elucidate the molecular mechanisms that control neural stem cell differentiation to GABAergic neurons. Intracellular calcium oscillations can modulate many cell processes like gene transcription, differentiation and even cell death. Spitzer and coworkers have already described in Xenopus laevis that increases in spontaneous Ca2+ spikes frequency favors glutamatergic differentiation, these oscillations depends on IP3 receptor activity, which can be modulated by mHtt. Therefore, in this project we aim to elucidate the role of Htt/mHtt in spontaneous calcium oscillations during differentiation and in cell fate choice due to pro-neural gene expression, by using a cell model (CTE) that resembles the embryo development in vitro. In addition, we will also investigate intracellular signaling pathways by which wild type Htt can control early embryo development, since the knockout is lethal before reaching gastrulation. | |
| News published in Agência FAPESP Newsletter about the scholarship: | |
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