The Department of Health Sciences is pleased to announce the first seminar in our 2024-25 Health Sciences Seminar Series, and this event will be held in-person, with a virtual option via Zoom (Zoom registration here - https://carleton-ca.zoom.us/meeting/register/tJ0ud-ivrz8rGdwtSSwSQNYyVunLSOdrr4BV)

Title: Functional genomics and cell-type specific mitochondrial profiling to investigate rare diseases

Abstract:
Mitochondria are widely known as the “powerhouse of the cell” as the site for cellular respiration and generation of ATP. However, none of these vital functions are possible without the presence of vitamins and cofactors, essential for bioenergetic enzymes. Vitamin B6 (pyridoxal 5’-phosphate, PLP) is one of such nutrients, necessary for the functioning of over 60 human metabolic enzymes, including reactions on heme and neurotransmitter biosynthesis. High-dose vitamin B6 is a treatment for B6-responsive disorders such as Pyridoxine-dependent epilepsy (PDE), alleviating seizures and enabling life. Despite its importance for human health, the factors that mediate PLP distribution, transport, homeostasis, and maintenance in different cellular compartments, especially in the mitochondria, are largely unknown. To address that, we employed a genome-wide CRISPRi screen and discovered a potential regulator of mitochondrial PLP. Loss-of-function of this gene is causal for a severe pediatric mitochondriopathy.. Here we will discuss the implications of genome screening technologies to discover novel mechanisms, potentially treatable disorders, and therapeutic targets.