Molecular Mechanisms of Organelle Formation in Bacteria

就像真核生物一样，许多细菌也使用脂质结合的细胞器

Much like their eukaryotic counterparts, numerous bacterial species use lipid-bounded organelles to execute essential, and at times toxic, biochemical reactions in a compartmentalized fashion. Despite their prevalence and importance to the health and survival of many organisms, relatively little is understood regarding the formation, function, and diversity of bacterial organelles. To advance the mechanistic study of lipid-bounded bacterial organelles, my group has developed two distinct model systems: magnetosomes of magnetotactic bacteria and the ferrosome compartments of diverse anaerobic microbes. Magnetosomes are lipid-bilayer invaginations of the cell membrane with a unique protein content, within which nanometer-sized iron-based magnetic crystals are produced. Individual magnetosomes are arranged into a chain with the help of an actin-like cytoskeleton, thus allowing magnetotactic bacteria to use geomagnetic fields as a simple guide for low oxygen environments. The cell biological features of magnetosomes make them ideal for understanding the evolution and molecular basis of organelle biogenesis and biomineralization in bacteria. The magnetic and physical properties of magnetosomes make them attractive targets for the development of biomedical applications including their use as contrast agents for magnetic resonance imaging, as drug delivery vehicles and as a medium for hyperthermic killing of tumor cells. More recently, my group has discovered a novel iron-accumulating lipid-bounded organelle named the ferrosome. Ferrosomes are formed through the action of a small number of genes and are found in diverse bacteria including resident members of the gut microbiome and opportunistic pathogens. The research program outlined in this proposal will leverage the expertise and existing knowledge within my group to explore three general areas of magnetosome and ferrosome biology. First, we will study the molecular components, biochemical activities, and cellular pathways that define the cell biological characteristics of bacterial organelles. Our current focus is to understand the mechanisms of membrane biogenesis, protein sorting, and subcellular arrangement for magnetosomes and ferrosomes. Second, we are interested in the biochemical output and cellular function of magnetosomes and ferrosomes. Using comprehensive genetic, chemical, and physiological assays we aim to understand how these organelles are integrated into the essential functions of their host organisms. Third, we look to exploit the natural diversity of magnetosome- and ferrosome-forming organisms to understand the common and unique evolutionary paths of organelle formation in bacteria. The combination of these approaches will shed light on the molecular blueprint and evolutionary diversity of bacterial compartments. In the process, we hope to devise more rational paths for synthetic re- engineering of magnetosomes and ferrosomes to deploy them more effectively in applied settings.