Cystic Fibrosis is caused by mutations in CFTR, with a deletion of a phenylalanine at position 508 (F508del-CFTR) representing the most common mutation. The F508del-CFTR protein exhibits a trafficking defect and is retained in the endoplasmic reticulum. Here we describe the development of a high-content screen based on a functional assay to identify proteins that correct the F508del-CFTR defect. Using a HEK293 MSR GripTite cell line that stably expresses F508del-CFTR, we individually co-expressed ϳ450 unique proteins fused to the Cl ؊ -sensitive YFP(H148Q/I152L) mutant. We then tested correction of F508del-CFTR function by the CI ؊ /l ؊ exchange method following stimulation with forskolin/IBMX/genistein, using quantitative recordings in multiple individual cells with a high-content (high-throughput) Cellomics KSR imaging system. Using this approach, we identified several known and novel proteins that corrected F508del-CFTR function, including STAT1, Endothelin 1, HspA4, SAPK substrate protein 1, AP2M1, LGALS3/galectin-3, Trkfused gene, Caveolin 2, PAP/REG3␣, and others. The ability of these correctors to rescue F508del-CFTR trafficking was then validated by demonstrating their enhancement of maturation (appearance of band C) and by cell surface expression of F508del-CFTR bearing HA tag at the ectodomain using confocal microscopy and flow cytometry. These data demonstrate the utility of highcontent analyses for identifying proteins that correct mutant CFTR and discover new proteins that stimulate this correction. This assay can also be utilized for RNAi screens to identify inhibitory proteins that block

BackgroundWith an ever increasing number of individuals living with chronic and terminal illnesses, palliative care as an emerging field is poised for unprecedented expansion. Today’s rising recognition of its key role in patients’ illnesses has led to increased interest in access to palliative care. It is known that homelessness as a social determinant of health has been associated with decreased access to health resources in spite of poorer health outcomes and some would argue, higher need. This article aims to discuss the current state of affairs with regards to accessing palliative care for the homeless in Canada.DiscussionRecent review of the literature reveals differential access to palliative care services and outcomes with differing socio-economic status (SES). Notably, individuals of lower SES and in particular, those who are homeless have poorer health outcomes in addition to poor access to quality palliative care. Current palliative care services are ill equipped to care for this vulnerable population and most programs are built upon an infrastructure that is prohibitive for the homeless to access its services. A preliminary review of existing Canadian programs in place to address this gap in access identified a paucity of sporadic palliative care programs across the country with a focus on homeless and vulnerably-housed individuals. It is apparent that there is no unified national strategy to address this gap in access.SummaryThe changing landscape of the Canadian population calls for an expansion of palliative care as a field and as many have put it, as a right. The right to access quality palliative and end of life care should not be confined to particular population groups. This article calls for the development of a unified national strategy to address this glaring gap in our healthcare provision and advocates for attention to and adoption of policy and processes that would support the homeless populations’ right to quality palliative care.