The molecular and physiological mechanisms of a new form of hereditary spastic paraparesis

The long-term goal of the proposed study is to determine the precise role of TECPR2 in intracellular vesicular trafficking and autophagy, and characterize the link between these processes and hereditary spastic paraparesis (SPG49). Our working hypothesis is that mutations in TECPR2 lead to specific defects in intracellular trafficking and autophagic processes manifested as a specific neuronal malfunction in the patients. The PhD student will combine biochemical and cell biological techniques with a gene-targeting approach to determine TECPR2 functions in cells from healthy and diseased tissue. Specifically, the PhD student will 1) establish an animal model for SPG49 and study the relationship between TECPR2 physiological function and neurodegeneration in vivo; 2) study the role of TECPR2 in axonal trafficking (to determine the link between cellular defects and disease) and in neuronal autophagic processes.