The Mechanism and Function of Organelle Hitchhiking - PROJECT SUMMARY The proper distribution of intracellular cargo is crucial for many fundamental biological processes. Yet how cargo transport is regulated in space and time, especially within a crowded cytosol, remains poorly understood. A novel mode of molecular motor-driven transport was recently discovered by the Reck-Peterson lab in the filamentous fungus Aspergillus nidulans, where peroxisomes “hitchhike” on early endosomes and require the protein PxdA. Hitchhiking was initially discovered in filamentous fungi and was later shown to transport mRNAs, peroxisomes, and ER tubules in yeast and mammalian cells. However, the mechanism and function of peroxisome hitchhiking remains unknown. PxdA is only present in the Pezizomycotina subdivision, one of the few fungal groups that produce secondary metabolites (SMs) which have implications in human health and disease. Notable examples of SMs include penicillin, lovastatin, and mycotoxins. Filamentous fungi rely on SMs as virulence factors, signaling molecules for development, and protection from environmental stresses. While many SM biosynthetic pathways have been well-described chemically, very little is known about how SM production is mapped onto a cellular context. The long-term goal of this project is to understand how organelle hitchhiking coordinates SM production to improve the industrial production of SMs that are beneficial for human health and to identify fungal- specific targets for anti-fungal therapeutics. This project will investigate the mechanism and function of organelle hitchhiking in Aspergillus nidulans using a combination of genetics, live-cell fluorescence microscopy, as well as in vitro biochemistry and biophysics techniques. My aims are to 1) determine the molecular mechanism of organelle hitchhiking, and 2) determine the physiological function of organelle hitchhiking in filamentous fungi. Together, my work will enhance our understanding of how organelle transport and positioning in filamentous fungi regulates SM production and development.
