The disclosure relates cells or cellular systems that express both a membrane protein and a binding domain directed to the membrane protein. Also, methods are provided that use such cells or cellular systems to produce higher amounts of the membrane proteins. Further, the cells or cellular systems can be used as tools for the structural and functional characterization of membrane proteins, as well as for screening and drug discovery efforts targeting membrane proteins.

The present invention relates to compositions and methods of use of anti-ADAMTS13 autoantibodies and fragments thereof. In one aspect, the invention includes a composition comprising an isolated anti-ADAMTS13 autoantibody or fragment thereof. In other aspects, methods are described for generating an in vivo model of thrombotic thrombocytopenic purpura (TTP) comprising introducing at least one anti-ADAMTS13 autoantibody or fragment thereof into a model organism and identifying an anti-autoimmune reagent for treating TTP.

A2M polypeptide compositions containing a non-natural bait region are disclosed. Methods of producing wild-type and variant A2M polypeptides and polynucleotides containing a non-natural bait region are also disclosed. The bait regions of the variant A2M polypeptides demonstrate enhanced protease inhibitory characteristics compared to wild-type A2M. Variant A2M polypeptides that demonstrate longer half-lives upon administration to an organism compared to wild-type A2M are disclosed. The A2M compositions are useful in treating a number of diseases and conditions including inflammation, chronic wounds, and diseases with a pathology associated with proteases.

The present invention relates to methods and compositions for treating and/or preventing a disease or disorder associated with abnormally high level of the IFP35 family of proteins, including IFP35 and NMI, methods and compositions for diagnosis, prognosis or treatment monitoring of a disease or disorder associated with abnormally high level of the IFP35 family of proteins, including IFP35 and NMI, and methods and compositions for identifying a modulator of the IFP35 family of proteins, including IFP35 and NMI.

It has been revealed that, from a pre-onset stage of Alzheimer's disease, enhancement of phosphorylations of MARCKS and the like causes abnormal spine formation or the like, consequently developing the disease. Moreover, it has also been revealed that the phosphorylations of MARCKS and the like are caused by PKC and the like, and further that b-raf is involved in the phosphorylation of a tau protein important for the progression of Alzheimer's disease. Thus, these proteins have been found to be target molecules useful in the diagnosis and treatment of Alzheimer's disease. In addition, it has also been revealed that, pre-onset in a stage of frontotemporal lobar degeneration also, b-RAF phosphorylation enhancement causes a decrease in the number of spines and the like, consequently developing the disease. Thus, b-RAF has been found to be a target molecule useful in the diagnosis and treatment of frontotemporal lobar degeneration.

The disclosure relates cells or cellular systems that express both a membrane protein and a binding domain directed to the membrane protein. Also, methods are provided that use such cells or cellular systems to produce higher amounts of the membrane proteins. Further, the cells or cellular systems can be used as tools for the structural and functional characterization of membrane proteins, as well as for screening and drug discovery efforts targeting membrane proteins.

The present application describes structures, systems, and methods for modeling and analysis of single-strand break (SSB) signaling and repair in a cell-free system. Also provided are methods of making the SSB structures and SSB signaling and repair systems. Methods and systems for identifying modulators of DNA damage response (DDR) activity for SSB repair are also described as well as methods of inhibiting SSB repair.

The present invention provides a novel secretion reducing agent and novel secretion reducing method for reducing extracellular vesicle secretion from cells. The extracellular vesicle secretion reducing agent of the present invention is characterized in that it contains an inhibitor of a serine synthesis pathway. The cells are, for example, cancer cells such as colorectal cancer cells, lung cancer cells, melanoma cells, breast cancer cells, pancreas cancer cells, and multiple myeloma cells.

Disclosed are methods, kits and cells for screening an inhibitor of association between candidate binding partners, such as for screening antagonists of amyloid peptides. The methods, kits and cells employ a reporter expression cassette and hybrid proteins. The reporter expression cassette encodes a reporter and comprises at least one DNA binding site. Each hybrid protein comprises a candidate binding partner and a component of a DNA binding protein and, upon association, form a DNA-binding complex capable of binding to the at least one binding site and inhibiting expression of the reporter. The methods, kits and cells find application, for example, in the identification of inhibitors that may be useful in treating diseases associated with protein aggregation, such as Alzheimer's Disease and Parkinson's Disease.

Disclosed are peptide conjugates comprising an active agent, a spacer moiety, and a dimeric collagen hybridizing peptide comprising a first and second collagen hybridizing peptide, a linker; and a branch point, wherein the first and second collagen hybridizing peptides comprise the sequence of at least (GXY)n, wherein G is glycine, wherein X and Y are any amino acid, and wherein n is any number between 3 and 12. Also disclosed are methods of detecting denatured collagen in a sample comprising contacting a composition comprising any one of the disclosed peptide conjugates to a sample, wherein the active agent comprises a therapeutic agent, and detecting the presence or absence of binding of the peptide conjugate to denatured collagen, the presence of binding indicating the presence of denatured collagen in the sample. Also disclosed are methods of treating a disease or injury involving collagen damage comprising administering to a subject having a disease or injury involving collagen damage any one of the disclosed peptide conjugates.