The disclosure describes novel systems, methods, and compositions for the manipulation of nucleic acids in a targeted fashion. The disclosure describes non-naturally occurring, engineered CRISPR systems, components, and methods for targeted modification of nucleic acids. Each system includes one or more protein components and one or more nucleic acid components that together target nucleic acids.

A living engineered glue system for performing autonomous mechanical repairs comprises a biofilm of microbial cells embedded in an extracellular matrix and operably linked in an environmentally-inducible, cell-cell communication genetic circuit to control gene expression.

Methods are described herein for generating beneficial compounds and/or materials such as bacteriocins that include contacting ‘challenger’ microbes with the ‘protagonist’ microorganisms. The challenger microbes do not directly manufacture the beneficial compounds and/or materials and instead stimulate the protagonist microorganisms to produce beneficial compounds and materials. The protagonist and/or challenger microorganisms can be administered to a subject so the beneficial compounds and/or materials can be made in vivo. Compositions and methods of using beneficial compounds and/or materials are also described herein.

Methods are described herein for generating beneficial compounds and/or materials such as bacteriocins that include contacting ‘challenger’ microbes with the ‘protagonist’ microorganisms. The challenger microbes do not directly manufacture the beneficial compounds and/or materials and instead stimulate the protagonist microorganisms to produce beneficial compounds and materials. The protagonist and/or challenger microorganisms can be administered to a subject so the beneficial compounds and/or materials can be made in vivo. Compositions and methods of using beneficial compounds and/or materials are also described herein.

The present invention relates to macromolecular complexes comprising micron-scale networks which include binding motifs thereon which allow the covalent bonding of the micron-scale networks to particles which provide nanoscale display surfaces. In particular the present invention relates to micron-scale networks of TMV coat proteins comprising a peptide tag (e.g. SpyTag) and particles providing a nanoscale display surface comprising GFP and a corresponding binding protein (e.g. SpyCatcher) wherein the peptide tag and binding protein pair are capable of spontaneously forming a covalent bond.

The present invention relates to macromolecular complexes comprising micron-scale networks which include binding motifs thereon which allow the covalent bonding of the micron-scale networks to particles which provide nanoscale display surfaces. In particular the present invention relates to micron-scale networks of TMV coat proteins comprising a peptide tag (e.g. SpyTag) and particles providing a nanoscale display surface comprising GFP and a corresponding binding protein (e.g. SpyCatcher) wherein the peptide tag and binding protein pair are capable of spontaneously forming a covalent bond.

Methods of and compositions for breaking down a biofilm or inhibiting, preventing or treating a microbial infection that produces a biofilm are disclosed, which involves administration of an interfering agent capable of specifically competing, titrating, or inhibiting the binding of an HU protein to a microbial DNA. By competing with HU proteins that bind to DNA scaffold in the biofilm, these interfering agents destabilize the biofilm leading to destruction and removal of the biofilm by the immune system. Further method and composition aspects are contemplated in relation to infections caused by bacteria that export an HU protein.

Methods of and compositions for breaking down a biofilm or inhibiting, preventing or treating a microbial infection that produces a biofilm are disclosed, which involves administration of an interfering agent capable of specifically competing, titrating, or inhibiting the binding of an HU protein to a microbial DNA. By competing with HU proteins that bind to DNA scaffold in the biofilm, these interfering agents destabilize the biofilm leading to destruction and removal of the biofilm by the immune system. Further method and composition aspects are contemplated in relation to infections caused by bacteria that export an HU protein.

Described herein is a chimeric antigen receptor (CAR) platform with the ability to (a) serve as an ON/OFF switch (with the ability for tenability/titrability), (b) sense multiple antigens and perform logic computations, and/or (c) independently regulate multiple signaling pathways. The compositions provided herein permit the degree of control and discrimination necessary to optimize CAR T cell therapy. Also described herein are cells comprising such compositions and the use of these compositions and/or cells in the treatment of cancer.

Described herein is a chimeric antigen receptor (CAR) platform with the ability to (a) serve as an ON/OFF switch (with the ability for tenability/titrability), (b) sense multiple antigens and perform logic computations, and/or (c) independently regulate multiple signaling pathways. The compositions provided herein permit the degree of control and discrimination necessary to optimize CAR T cell therapy. Also described herein are cells comprising such compositions and the use of these compositions and/or cells in the treatment of cancer.