The present invention is directed to a method, kit, system and fusion protein for detecting binding to an ADP-ribosyl group or a polymer thereof, wherein said group or polymer is coupled to a peptide or protein, the method comprising the steps of: i) providing a first entity comprising a first label or tag, said entity comprising an amino acid sequence comprising a cysteine residue whereto at least one ADP-ribosyl group or an analog thereof is coupled via an S-glycosidic bond; ii) contacting in an assay said first entity with a second entity, said second entity being or suspected of being capable of binding to an ADP-ribosyl group or polymer thereof coupled to a peptide or protein; and iii) measuring a signal derived from said first label or localized by said tag, wherein the signal detected is different or is localized differently when said second entity binds to said at least one ADP-ribosyl group of the first entity from the signal detected when the binding interaction between said second entity and said ADP-ribosyl group has not occurred. The kit of the present invention provides means to perform the method of the invention.

Provided herein are split reporter systems for detecting poly-ADP ribose polymerase activity in living systems. In some aspects, the split reporter systems comprise a first fusion protein comprising a first fragment of a reporter protein functionally linked to a first poly-ADP ribose binding moiety; and a second fusion protein comprising a second fragment of the reporter protein functionally linked to a second poly-ADP ribose binding moiety wherein the first and second fragments of the reporter protein are each non-functional and capable of recombining, optionally in the presence of a substrate, to form a functional reporter protein capable of producing a detectable signal. Also provided are methods of use thereof.

There is provided protein biomarkers and methods for their use in diagnosing and treating Inflammatory Bowel Disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD) as well as methods for assessing the severity of the diseases.

The present invention is related to diagnostic, treatment and compound screening methods related to dry age-related macular degeneration (dry AM D). In select embodiments, the methods comprise determining expression or activity levels of NAD-dependent deacetylase sirtuin-1 (SI RT-1), AM P-activated protein kinase (AM PK), poly(adenosine diphosphate ribose) poly-merase-2 (PARP2), peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-I) and/or mRNA levels of RAC-gamma serine/threonine-protein kinase (AKT3). In general, higher levels of PARP2, lower levels of PGC-I or AKT3 and/or higher acetylation levels of PGC-I in the samples are indicative that the subject or cells from which the samples are obtained are susceptible or are suffering from dry AMD.

In one embodiment, the present invention provides methods of modulating the deacetylase activity of SIRT1 in one or more cell by modifying the binding affinity of lamin A to SIRT1 via one or more interaction modifying compound. In another embodiment, the present invention provides methods of screening SIRT1-activating/inhibiting compounds based on the interaction between lamin A and SIRT1 proteins and SIRT1-activating property of lamin A. In another embodiment, the present invention provides uses of SIRT1-activating compounds to treat patient(s) suffering from metabolic and/or aging-related degenerative diseases, and uses of SIRT1-inhibiting compounds to treat human malignancies.

There is provided protein biomarkers and methods for their use in diagnosing and treating Inflammatory Bowel Disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD) as well as methods for assessing the severity of the diseases.

The present invention generally relates to therapeutic inhibition of protein arginine methyltransferase 5 (PRMT5). In particular, cell lines having MTAP loss and increased intracellular MTA concentrations show selective dependence on PRMT5. Thus, the invention also relates to methods of identifying and treating PRMT5-related diseases in subjects or tissues which have an MTAP deficiency, alone or in combination, with a second agent that reduces MTAP activity and/or increases intracellular MTA levels, and/or provides an MTA analogs to the cell or tissue. The invention also relates to the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas System and components thereof. More specifically, the present invention relates to the delivery, use and therapeutic applications of the CRISPR-Cas systems and compositions in tumor cells ex vivo and/or in vivo. For example using methods disclosed herein, cells can be sensitized to PRMT5 inhibition.

The invention provides methods and compositions for enhancing the efficacy of cancer therapies through modulation of BAL1 and/or BBAP. Also provided are methods for predicting the efficacy of cancer therapies or treating cancer in a subject through modulation of BAL1 and/or BBAP. Further provided are methods for identifying compounds that are capable of modulating BAL1-BBAP complexes.

There is provided protein biomarkers and methods for their use in diagnosing and treating Inflammatory Bowel Disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD) as well as methods for assessing the severity of the diseases.

There are provided, inter alia, methods and reagents for labeling nucleic acids.