Abstract: The present invention relates to components, systems, and methods transcriptional modification (e.g., transcriptional activation) or methods of identifying transcriptional effectors based on Cas9-transcription effector fusion protein and gRNA sequence targeting.

Abstract: The invention provides a composition for use as a medicament, comprising cells of a recombinant microorganism capable of producing increased amounts of one or more of 5-hydroxytryptophan (5-HTP), 5-hydroxytryptamine (5-HT) and tryptamine (TRM) as compared to the non-recombinant microorganism from which it was derived. The composition finds use in preventing and/or treating TRM-; 5-HTP-, or 5-HT-related disorders of the central nerve system (CNS); enteric nervous system (ENS); gastro intestine (GI) and metabolism in a mammal, and may be orally administered to a mammal in need thereof. Additionally, a composition comprising cells of a recombinant microorganism capable of producing melatonin is provided for use as a medicament, such as for treatment of depression, dementia, cancer and sleep disorder.

Abstract: The present invention relates to utilizing engineered horizontal gene transfer elements and high-throughput selection strategies to tag and retrieve genetically modified native commensal strains from the mammalian gut. In certain aspects, the present invention relates to methods wherein isolated bacteria from the mammalian gut microbiome that were amenable to genetic manipulation were redeployed back into the mammalian subject as host-optimized engineerable probiotics.

Abstract: Provided herein are methods and systems to record temporal biological signals into the genomes of engineered cells (e.g., genomes of a bacterial population) using the CRISPR-Cas system.

Abstract: Disclosed herein are systems, methods and components for targeted gene editing. Certain embodiments relate to a Cas protein lacking catalytic activity fused to a transposase. Also disclosed are systems that involve a Cas-transposase fusion protein, gRNA sequences and at least one mini-transposon for directing transpositions at user-defined genetic loci. Implementations of the system may involve disruption of a target gene or insertion of a payload sequence into a target nucleic acid.

Abstract: The present invention relates to components, systems, and methods transcriptional modification (e.g., transcriptional activation) or methods of identifying transcriptional effectors based on Cas9-transcription effector fusion protein and gRNA sequence targeting.