The role of RAB24 in healthy and diseased neurons
The goal in this project is to elucidate the physiological function of the small GTPase RAB24 in neuronal cells. We showed recently that RAB24 is required for the clearance of autolysosomes under nutrient-rich conditions (Ylä-Anttila et al. 2015, Autophagy 10:1833-48). This suggests that RAB24 is needed for basal autophagy, which is particularly important in postmitotic cells like neurons that are not able to dilute non-functional organelles and aggregate-prone proteins by cell division. Our results also showed that RAB24 facilitates the degradation of mutant huntingtin protein, which forms aggregates and causes the hereditary neurodegenerative Huntington’s disease. Others have revealed that huntingtin is normally degraded via autophagy. Importantly, mutations in RAB24 were shown to cause hereditary ataxia in dogs, due to loss of cerebellar Purkinje neurons because of defective autophagy (Agler et al, 2014, PLoS Genet 10, e1003991). These findings indicate that RAB24 is important for the neuronal survival and that RAB24 dysfunction causes disease.
To elucidate the physiological functions of RAB24 in neurons, the PhD student will investigate the effect of the disease-causing RAB24 mutation on both RAB24 function and autophagy in neuronal cells, using cell and molecular biological methodologies available on our laboratory and new assays that we will develop. In addition, the PhD student will search for RAB24 interacting proteins, and the most interesting hits in these screens will be verified in neuronal cell cultures and in mouse tissues. Co-immunoprecipitations and co-localization of endogenous proteins in mouse tissues will be done in collaboration with the Boya laboratory in Madrid, Spain. Finally, to elucidate in which regions of the central nervous system RAB24 is expressed and likely to play roles in neuronal survival, the PhD student will clarify the expression of RAB24 protein in the central nervous system of mice of different ages.
Location: University of Turku, Department of Biomedicine, Turku, Finland
Supervisor: Prof. Dr. Eeva-Liisa Eskelinen
Length of appointment: 36 months (3 years) + 12 months (1 year)
Indicative Starting date: May 2018
Type of Contract: temporary
Hours per week: 36 (full time)
Deadline for application is 9 January 2018 at 23.59 h Brussels time zone gmt.
UPDATE: This vacancy is now closed.
More information about the host laboratory can be found at http://www.helsinki.fi/autophagy