This project aims to develop and investigate human cortical brain organoids (hCBOs) derived from induced pluripotent stem cells (iPSCs) to elucidate molecular mechanisms and assess potential treatment strategies for PDHA1-related pyruvate dehydrogenase complex (PDHc) deficiency. The study will integrate structural, metabolic, and functional assessments to identify disease-related alterations and evaluate therapeutic interventions. The first three months will focus on generating hCBOs from patient-derived and control iPSCs. From months four to six, neuronal structure and development will be characterized at the molecular level. Single-cell RNA sequencing (scRNA-seq) will be performed to identify cell-type-specific transcriptional alterations in PDHA1-deficient organoids. Parallel metabolic analyses will begin, using metabolomic and proteomic profiling to determine how PDHA1 deficiency affect glycolysis, oxidative phosphorylation, and overall metabolic function of hCBOs.
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Job Type
Full-time
Career Level
Entry Level
Education Level
Ph.D. or professional degree