Transporting cellular cargo with spatial and temporal precision is critical for many processes in all cells. Different cell types and organisms use diverse machineries for long-distance cargo transport. For example, mammalian cells and many filamentous fungi transport cargo using the microtubule-based motors dynein and kinesin, while yeast use myosin motors on actin cytoskeleton tracks. Despite a general understanding of cellular transport and the motors involved, little is known about how similar transport machineries are adapted by specific cell types or organisms. Dr. Christensen’s current research investigates canonical (motor-driven) and non-canonical cargo transport. In this proposal, she will investigate how both modes of transport have evolved in different organisms using an innovative approach in which evolutionary hypotheses are directly tested using comparative cell biology in fungal and mammalian cells. Defects in transport are particularly prevalent in neurological disorders such as Alzheimer’s, Huntington’s and ALS. Examining how diverse cell types differently use the transport machinery is directly applicable to understanding how transport defects lead to cell-specific diseases. In Aim 1, Dr. Christensen will investigate how regulators of motor-driven transport have evolved in fungi and human cells. In her current research and the K99 phase of this award, she will investigate how the gene expansion and functional diversification of the ‘FHF’ protein complex allows dynein to bind multiple cargos in human cells. For the R00 phase of this award, Dr. Christensen will identify and characterize novel dynein regulators using evolutionary analysis and comparative cell biology in A. nidulans and human cells. In Aim 2, Dr. Christensen will investigate a non-canonical form of transport known as ‘hitchhiking’. In hitchhiking, a cargo attaches to and is co-transported with another cargo to achieve motility. Hitchhiking has been demonstrated to occur in two evolu