Post Doctoral Fellow-MSH-30001-002

Using Human Cortical Brain Organoids to Uncover Molecular Mechanisms and Treatment Efficacy in PDHA1-Related PDHc Deficiency

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, us...