Masterstudent

Project for master thesis at the Institute of Diagnostic Laboratory Medicine, Clinical Chemistry and Pathobiochemistry - Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum Title: “Characterization of Molecular Targets in Disease Models of Hereditary Spastic Paraplegias for Diagnostic, Prognostic, and Therapeutic Development” Project Description Hereditary spastic paraplegia (HSP) comprises a genetically heterogeneous group of neurodegenerative disorders (SPGs) characterized by progressive lower limb weakness and spasticity caused by degeneration of corticospinal motor neuron axons. Mutations in HSP￾associated genes result in functional alterations of the corresponding proteins, ultimately disrupting cellular homeostasis. Similar to many other inherited neurodegenerative diseases, no common molecular targets for diagnostic, prognostic, or therapeutic interventions have yet been established for HSP. This Master’s project aims to investigate the molecular and functional mechanisms underlying a subgroup of HSPs, with a particular focus on SPG11, SPG15, and SPG48. The objective is to identify shared molecular targets among these pathomechanistically related HSP forms. Using established murine models for SPG11, SPG15, and SPG48, a multiparametric approach will be employed to validate candidate targets identified through OMICs-based analyses of various tissues and cellular systems, including murine brain tissue and immortalized mouse embryonic fibroblasts (iMEFs). The project involves mammalian cell culture (mouse and human cell lines) as well as a broad range of biochemical and molecular biology techniques, including SDS-PAGE, Western blotting, immunoprecipitation, qPCR-based RNA analysis, fluorescence microscopy, and immunohistochemistry on fixed mouse tissues. We are seeking a highly motivated Master’s student pursuing a degree in Biomedicine or a related field. Interested candidates are invited to submit their CV and motivation letter to Dr. Mukhran Khundadze, Contact: Mukhran.Khundadze@charite.de.