Dr. Jonathan Stefely, MD, PhD, Massachusetts General Hospital
Mitochondrial proteins and pathways in a divergent protozoan pathogen
Across the eukaryotic tree of life, mitochondria have diverged markedly through a billion years of evolution, providing a rich diversity of biology with the potential to lend insights through “comparative metabolism”. The mitochondrion is also a proven drug target for eukaryotic pathogens—including protozoan organisms that collectively afflict nearly one billion people each year—yet current agents are limited by emerging resistance or toxicity. Focusing on one such protozoan pathogen that is a free-living amoeba, we used pan-lifecycle long-read RNA sequencing to improve nuclear genome annotation accuracy from 52% to 98% and then used mass spectrometry to define a new high-quality mitochondrial proteome inventory. This protozoan “MitoCarta” has >1100 proteins, over one-third of which are uncharacterized and have no homologs in animals or fungi. We are now integrating complexomics, perturbation profiling, microscopy, classical biochemistry, and structural biology to begin mapping these protozoan-specific MitoCarta proteins into functional complexes and metabolic pathways. These mechanistic studies are simultaneously nominating new drug targets and revealing new biology, even providing insight into our own ancient evolutionary history.
The colloquium will feature invited lecturers and bring together metabolism researchers to share ideas, expertise and resources. Visiting lecturers will present a seminar on their work (time and dates will vary) as well as meet with members of the metabolism community.