Provided herein are methods and systems for screening a candidate agent to determine whether the candidate agent modulates an activity of cultured cells. Compositions for screening a candidate agent are also provided herein.

The present invention provides novel mutations identified in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that can be used for a more accurate diagnosis of cystic fibrosis (CF) and CF related disorders. Methods for testing a sample obtained from a subject to determine the presence of one or more mutations in the CFTR gene are provided wherein the presence of one or more mutations indicates that the subject has CF or a CF related disorder, or is a carrier of a CFTR mutation.

The present invention relates to detecting cleavage activity of an enzyme. The various aspects of the invention include an enzyme detection device, kit, method and use for detecting or measuring the presence in a test sample of the activity of an enzyme capable of cleaving a substrate. The invention also relates to indicator and binding molecules useful for carrying out the invention. The enzyme substrate contains a hidden binding site which is only revealed upon cleavage by the enzyme.

The present invention relates to detecting cleavage activity of an enzyme. The various aspects of the invention include an enzyme detection device, kit, method and use for detecting or measuring the presence in a test sample of the activity of an enzyme capable of cleaving a substrate. The invention also relates to indicator and binding molecules useful for carrying out the invention. The enzyme substrate contains a hidden binding site which is only revealed upon cleavage by the enzyme.

Disclosed herein are methods for detecting protein expression in an individual diagnosed with cystic fibrosis. The methods, in certain aspects, include the steps of obtaining a sample from said individual and detecting expression in said sample of each protein of a protein set. The method may further include the step of determining expression level of one or more proteins of the protein set. The disclosed methods may be used to predict one or more clinical parameters in an individual having cystic fibrosis.

The present invention provides novel mutations of the CFTR gene related to cystic fibrosis or to conditions associated with cystic fibrosis. Also provided are probes for detecting the mutant sequences. Methods of identifying if an individual has a genotype containing one or more mutations in the CFTR gene are further provided.

The present disclosure provides, inter alia, a recombinant engineered deubiquitinase (DUB) and methods for treating or ameliorating an inherited ion channelopathy, such as long QT syndrome, Brugada syndrome, or cystic fibrosis, in a subject. Further provided are methods for screening mutations causing such inherited ion channelopathies for a trafficking-deficient mutation that is treatable by the recombinant engineered DUB disclosed herein.

Certain embodiments of the invention provide a method of quantifying ubiquitin-like modification in a test protein sample comprising: a) contacting the test protein sample with a compound of formula (I) to provide a first labeled test protein sample; b) contacting the first labeled test protein sample with a first enzyme, wherein the first enzyme cleaves the ubiquitin-like modification from all modified amino acid residues, to provide a second labeled test protein sample; c) contacting the second labeled test protein sample with a compound of formula (II) to provide a third labeled test protein sample; and d) measuring the molecular weight of the protein(s) in the third labeled test protein sample to quantify the ubiquitin-like modification in the test protein sample, wherein the compound of formula I is isotopically labeled; the compound of formula II is isotopically labeled; or the compound of formula I and the compound of formula II are differentially isotopically labeled.

The present invention is related to novel methods for diagnosing and treating acute pulmonary exacerbation in subjects in need thereof.

Provided herein are flexible, microfluidic epidermal systems and methods useful in the analysis of biofluids for biomarkers corresponding to a variety of conditions and methods of use. The provided systems configured to create conformal contact with the skin to allow for medical testing or screening, either in situ or later external laboratory testing. The described devices and methods may be used for cystic fibrosis screening, glucose monitoring, drug and/or alcohol testing, creatinine monitoring, urea monitoring, pH measurement and dialysis treatment efficacy testing.