The Journal of Physiology has a long and distinguished history of publishing original observations using non-mammalian tractable model systems that have fundamentally informed understanding of mammalian membrane transport processes. Some specific examples include a pioneering investigation of the selective barrier function of epithelia using frog skin (Waymouth Reid, 1890), an elegant illustration of ion channel and Na+–K+ pump activity in giant axons from the cuttlefish and squid (Hodgkin & Keynes, 1955) and an early demonstration of Na+-dependent sugar transport in the toad intestine (Csaky & Thale, 1960). Such physiological demonstrations of transport function have, in more recent times, been supported by the explosion in available genomic information that has, in turn, greatly improved our understanding of conserved biological functions across many species. Likewise, the high degree of similarity in protein structures from prokaryotes and eukaryotes, despite limited sequence homology, also points towards essential and sustained biological roles. Thus, prokaryotic transporter structures can provide key information concerning the way in which mammalian transport proteins are likely to function. A series of talks on the topic of emerging models for investigation of mammalian membrane transport and trafficking were presented on Sunday 21 April 2013 as part of the American Physiological Society programme of symposia at the Experimental Biology 2013 meeting. The session was held in the Boston Convention & Exhibition Center. The symposium was sponsored by The Physiological Society and The Journal of Physiology. The topics covered in this symposium emphasized the utility of so-called ‘lower organisms’ and how they can be used to improve our understanding of mammalian membrane transport and trafficking. The symposium opened with a presentation by Aravind Penmatsa on how the elucidation of the crystal structure of the amino acid transporter LeuT, from the thermophilic bacterium Aquifex aeolicus, has revolutionized our understanding of mammalian neurotransmitter transporter stucture and function (Penmatsa & Gouaux, 2014). The availability of the LeuT crystal has provided a structural basis to determine the action of antidepressants on the SLC6 family of human biogenic amine transporters (Wang et al. 2013). The next speaker, Britta Spanier, highlighted clear similarities in the mechanisms of transcriptional and functional regulation of the intestinal di/tripeptide transporter PepT1 in the gut of the nematode Caenorhabditis elegans and the commonly used cell culture model of the human small intestinal epithelium, the Caco-2 cell monolayer (Spanier, 2014). In both cases, PepT1 is regulated by the intracellular amino acid pool and functional activity of the co-expressed Na+–H+ exchanger NHE3. Tiziano Verri continued the theme of intestinal absorption of protein by providing a comprehensive review of the genomic and functional information currently available about PepT1 from a great number of studies using teleost fish (Romano et al. 2014). Intestinal protein absorption is such a fundamental biological process that modifications of the PepT1 transporter protein in different teleosts allow adaptation to extremes of temperature, pH and substrate availability. This information not only provides useful tips on how the mammalian PepT1 could be modified to enhance transport but also provides valuable information for optimization of feed for commercially valuable fish. Linda Stuart gave an elegant presentation on how animals (ranging from the fruitfly Drosophila melanogaster to mammals) sense pathogens (Stuart et al. 2013) and how phagosome acidification following phagocytosis of Gram-positive and Gram-negative bacteria takes place via distinct mechanisms (Sokolovska et al. 2013). The session was completed by a short presentation by Bill Harvey on a novel theory that considers how a K+ pump, comprising a H+ V-ATPase and a K+–H+ antiporter, originally discovered in the caterpillar midgut, might contribute to auditory mechanosensory transduction in the mammalian cochlea (Harvey & Xiang, 2012). The topics discussed in this symposium where diverse, but the common thread is clear. Our understanding of mammalian physiology is enhanced greatly by information obtained from studies of diverse organisms, including prokaryotes, fish, flies and worms.