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The cystic fibrosis transmembrane regulator (CFTR) is a multi-domain integral membrane protein central to epithelial fluid secretion (see Chapter 21). Its activity is defective in the recessive genetic disease cystic fibrosis (CF). The most common CF-causing mutation is F508del in t ...

The cystic fibrosis transmembrane conductance regulator (CFTR) is a multi-domain membrane chloride channel whose activity is regulated by ATP at two nucleotide-binding domains (NBD1 and NBD2) and by phosphorylation of the regulatory (R) region. The NBDs and the R region have functiona ...

The patch-clamp technique is a powerful and versatile method to investigate the cystic fibrosis transmembrane conductance regulator (CFTR) Cl– channel, its malfunction in disease and modulation by small molecules. Here, we discuss how the molecular behaviour of CFTR is investigated ...

This chapter introduces the various techniques to asses the function of CFTR. The numerous functional interactions of CFTR and cellular properties affected by CFTR will be described initially. This will be followed by sections explaining the importance of patch clamping and double ele ...

CFTR is the only member of the ABC (ATP-binding cassette) protein superfamily known to function as an ion channel. Most other ABC proteins are ATP-driven transporters, in which a cycle of ATP binding and hydrolysis, at intracellular nucleotide binding domains (NBDs), powers uphill substrate ...

Over 1600 novel sequence variants in the CFTR gene have been reported to the CF Mutation Database (http://www.genet.sickkids.on.ca/cftr/Home.html). While about 25 mutations are well characterized by clinical studies and functional assays, the disease liability of most of the remain ...

The CFTR Folding Consortium (CFC) was formed in 2004 under the auspices of the Cystic Fibrosis Foundation and its drug discovery and development affiliate, CFF Therapeutics. A primary goal of the CFC is the development and distribution of reagents and assay methods designed to better unders ...

Animal models of human diseases are critical for dissecting mechanisms of pathophysiology and developing therapies. In the context of cystic fibrosis (CF), mouse models have been the dominant species by which to study CF disease processes in vivo for the past two decades. Although much has been ...

When primary human airway epithelial (hAE) cells are grown in vitro on porous supports at an air–liquid interface (ALI), they recapitulate in vivo morphology and key physiologic processes. These cultures are useful for studying respiratory tract biology and diseases and for testing new c ...

This section of Cystic Fibrosis Protocols and Diagnosis focuses on resources available to facilitate the activities of the research community in the field of cystic fibrosis (CF). An overview of the protocols and resources described in subsequent chapters of this book section is provide ...

Lipid analysis has been a crucial source of information in cystic fibrosis (CF). New methodologies for qualitative and quantitative lipidomics allow evaluation of a large number of samples, of special interest in patient screening for diagnostic and prognostic biological markers, as ...

As several genomes have been sequenced, post-genomic approaches like transcriptomics and proteomics, identifying gene products differentially expressed in association with a given pathology, have held promise both of understanding the pathways associated with the respec ...

The cystic fibrosis transmembrane conductance regulator (CFTR) does not function in isolation, but rather in a complex network of protein–protein interactions that dictate the physiology of a healthy cell and tissue and, when defective, the pathophysiology characteristic of cys ...

Differential proteomics represents an enticing strategy to unmask the proteins involved in CF pathogenesis and to discover potential therapeutic targets and/or markers of disease progression. Quantitative proteomics is possible nowadays owing to the recent progress in prot ...

To understand the links between CFTR mutations and the development of cystic fibrosis (CF) phenotypes, it is imperative to study the transcriptome in affected cell types. Microarray expression profiling provides a platform to study global gene expression in detail. This approach may pr ...

Cystic fibrosis (CF) is a disease that manifests itself in the context of cell, tissue, and organismal (patho)physiology. While a strong focus on the cystic fibrosis transmembrane conductance regulator (CFTR) since its discovery in 1989 has dominated the field with a wealth of experiments t ...

Many bacteria can be detected in CF sputum, pathogenic and commensal. Modified Koch’s criteria for identification of established and emerging CF pathogens are therefore described. Methods are described to isolate bacteria and to detect bacterial biofilms in sputum or lung tissue from CF ...

The major phenotype of CF is the accumulation of mucus, a phenomenon whose relation to the dysfunctional CFTR is still not fully understood. This means that studies of mucus and its main component, the mucins, are important. Due to the large size and high glycosylation level, such questions need spec ...

The airways are continuously challenged by a variety of stimuli including bacteria, viruses, allergens, and inflammatory factors that act as agonists for G protein-coupled receptors (GPCR). Intracellular calcium (Ca2+ i) mobilization in airway epithelia in response to extracell ...

Human airways are kept sterile by a mucosal innate defense system that includes mucus secretion. Mucus is secreted in healthy upper airways primarily by submucosal glands and consists of defense molecules mixed with mucins, electrolytes, and water and is also a major component of sputum. Muc ...