Abstract: The present disclosure relates to methods for treating subjects having a substance use disorder (SUD) with 4-(3-cyanophenyl)-6-pyridinylpyrimidine mGlu5 negative allosteric modulators. Specifically, in some embodiments, this disclosure relates to methods of treating a subject having SUD who is at risk of relapse to alcohol use. In some embodiments, this disclosure relates to methods of promoting remission in a subject having SUD. In some embodiments, the SUD is alcohol use disorder (AUD), opioid use disorder (OUD), or a stimulant use disorder such as cocaine use disorder (CUD).

Abstract: Compositions and methods for light controlled protein-protein interactions in a living cell. Two interacting PICL (protein interaction controlled by light) polypeptides are provided. The first polypeptide comprises an LOV (Light, Oxygen or Voltage) domain, which domain is a light sensor that uses flavin mononucleotide (FMN) as a chromophore. The second polypeptide, specifically interacts with the L polypeptide upon light activation of the LOV domain. One or both of the polypeptides are fused to a cellular protein of interest. Upon exposure to light, a targeted interaction between cellular proteins occurs. The ability to regulate protein-protein interactions with subcellular resolution using light is useful for controlling biochemical processes such transcription, receptor activation, protein degradation, synapse formation, etc. in cells and animals.

Abstract: Compositions and methods for light controlled protein-protein interactions in a living cell. Two interacting PICL (protein interaction controlled by light) polypeptides are provided. The first polypeptide comprises an LOV (Light, Oxygen or Voltage) domain, which domain is a light sensor that uses flavin mononucleotide (FMN) as a chromophore. The second polypeptide, specifically interacts with the L polypeptide upon light activation of the LOV domain. One or both of the polypeptides are fused to a cellular protein of interest. Upon exposure to light, a targeted interaction between cellular proteins occurs. The ability to regulate protein-protein interactions with subcellular resolution using light is useful for controlling biochemical processes such transcription, receptor activation, protein degradation, synapse formation, etc. in cells and animals.

Abstract: The present invention provides compositions and methods for investigating the structural basis of the activation process of CRAC channels, which are essential for T-lymphocyte activation and adaptive immunity. The invention also provides compositions and methods to design, identify and evaluate agents that modulate calcium signaling by regulating the interaction between STIM and Orai proteins. The invention also provides therapeutic agents for cases of immunological disorders, compromised immune function, organ transplantation, or thrombosis.