Abstract: Described herein are novel biological converter switches that utilize modular components, such as genetic toggle switches and single invertase memory modules (SIMMs), for converting analog inputs to digital outputs, and digital inputs to analog outputs, in cells and cellular systems. Flexibility in these biological converter switches is provided by combining individual modular components, i.e., SIMMs and genetic toggle switches, together. These biological converter switches can be combined in a variety of network topologies to create circuits that act, for example, as switchboards, and regulate the production of an output product(s) based on the combination and nature of input signals received.

Abstract: Aspects of the present disclosure provide synthetic-biology platforms for in vivo genome editing, which enable the use of live cell genomes as “tape recorders” for long-term recording of event histories and analog memories.

Abstract: Described herein are novel biological converter switches that utilize modular components, such as genetic toggle switches and single invertase memory modules (SIMMs), for converting analog inputs to digital outputs, and digital inputs to analog outputs, in cells and cellular systems. Flexibility in these biological converter switches is provided by combining individual modular components, i.e., SIMMs and genetic toggle switches, together. These biological converter switches can be combined in a variety of network topologies to create circuits that act, for example, as switchboards, and regulate the production of an output product(s) based on the combination and nature of input signals received.

Abstract: Various aspects and embodiments of the invention are directed to high-throughput phage-engineering methods and recombinant bacteriophages with tunable host ranges for controlling phage specificity.

Abstract: The invention provides, inter alia, recombinase-based systems that provide for integrated logic and memory in living cells.

Abstract: The present disclosure provides, in some aspects, versatile intestinal protein delivery systems deploying engineered human gut commensals of the Bacteroides species to secrete heterologous, therapeutic proteins via outer membrane vesicles (OMVs).

Abstract: We have created novel engineered genetic counter designs and methods of use thereof that utilize DNA recombinases to provide modular systems, termed single invertase memory modules (SIMMs), for encoding memory in cells and cellular systems. Our designs are easily extended to compute to high numbers, by utilizing the >100 known recombinases to create subsequent modules. Flexibility in our engineered genetic counter designs is provided by daisy-chaining individual modular components, i.e., SIMMs together. These modular components of the engineered genetic counters can be combined in other network topologies to create circuits that perform, amongst other things, logic and memory. Our novel engineered genetic counter designs allow for the maintenance of memory and provide the ability to count between discrete states by expressing the recombinases between their cognate recognition sites.

Abstract: Various aspects and embodiments of the invention are directed to high-throughput phage-engineering methods and recombinant bacteriophages with tunable host ranges for controlling phage specificity.

Abstract: Provided herein are recombinase-based frameworks for building state machines in vitro and in vivo by using chemically controlled DNA excision and inversion operations to encode state in DNA sequence.

Abstract: Provided herein are microorganisms engineered with heme-responsive transcription factors and genetic circuits. Also provided are methods for using engineered microorganisms to sense bleeding events and treat bleeding in vivo.

Abstract: Aspects of the invention relate to the engineering of biological nanostructures and materials.

Abstract: Various aspects and embodiments of the present disclosure relate to methods and compositions that combine multiple mammalian RNA regulatory strategies, including RNA triple helix structures, introns, microRNAs, and ribozymes with Cas-based CRISPR transcription factors and ribonuclease-based RNA processing in human cells. The methods and compositions of the present disclosure, in some embodiments, enable multiplexed production of proteins and multiple guide RNAs from a single compact RNA-polymerase-II-expressed transcript for efficient modulation of synthetic constructs and endogenous human promoters.

Abstract: Various aspects and embodiments provided herein are directed to compositions that include at least one nanoparticle linked to a first polypeptide, and a biologically synthesizable polymer linked to at least one second polypeptide that binds covalently to the first polypeptide. Other aspects and embodiments provided herein are directed to methods of producing the foregoing compositions and components therein.

Abstract: Compositions, methods, and kits are provided which involve novel fusion protein-based adhesives for use in medical and marine applications. In some aspects, the novel fusion proteins comprise an adhesive domain (e.g., derived from an adhesive protein of a marine organism) and an amyloid domain (e.g., derived from a bacterial amyloid protein). Also provided are copolymers and fibers of the fusion proteins.

Abstract: This disclosure provided methods of cloning a phage genome. Also provided are methods of making a recombinant phage genome. In some embodiments the phage genome is engineered to comprise a heterologous nucleic acid sequence, for example a sequence comprising an open reading frame. In some embodiments the phage genome is cloned in a yeast artificial chromosome. Recombinant phage genomes and recombinant phage are also provided. In some embodiments the methods are high throughput methods such as methods of making aa plurality of recombinant phage genomes or recombinant phage. Collections of recombinant phage genomes and recombinant phage are also provided.

Abstract: The invention relates to methods and compositions that enable the rapid generation of high-order combinations of genetic elements, and that provide a barcoded basis for rapid characterization of the specific combination of genetic elements encoded within a single cell or in a pooled population.

Abstract: Described herein are novel biological circuit chemotactic converter that utilize modular components, such as genetic toggle switches and single invertase memory modules (SIMMs), for detecting and converting external inputs, such as chemoattractants, into outputs that allow for autonomous chemotaxis in cellular systems. Flexibility in these biological circuit chemotactic converter is provided by combining individual modular components, i.e., SIMMs and genetic toggle switches, together. These biological converter switches can be combined in a variety of network topologies to create network systems that regulate chemotactic responses based on the combination and nature of input signals received.

Abstract: This disclosure provided methods of cloning a phage genome. Also provided are methods of making a recombinant phage genome. In some embodiments the phage genome is engineered to comprise a heterologous nucleic acid sequence, for example a sequence comprising an open reading frame. In some embodiments the phage genome is cloned in a yeast artificial chromosome. Recombinant phage genomes and recombinant phage are also provided. In some embodiments the methods are high throughput methods such as methods of making a plurality of recombinant phage genomes or recombinant phage. Collections of recombinant phage genomes and recombinant phage are also provided.

Abstract: The present invention relates to the treatment and prevention of bacteria and bacterial infections. In particular, the present invention relates to engineered bacteriophages used in combination with antimicrobial agents to potentiate the antimicrobial effect and bacterial killing by the antimicrobial agent. The present invention generally relates to methods and compositions comprising engineered bacteriophages and antimicrobial agents for the treatment of bacteria, and more particularly to bacteriophages comprising agents that inhibit antibiotic resistance genes and/or cell survival genes, and/or bacteriophages comprising repressors of SOS response genes or inhibitors of antimicrobial defense genes and/or expressing an agent which increases the sensitivity of bacteria to an antimicrobial agent in combination with at least one antimicrobial agent, and their use thereof.

Abstract: The invention relates to methods and compositions that enable the rapid generation of high-order combinations of genetic elements, and that provide a barcoded basis for rapid characterization of the specific combination of genetic elements encoded within a single cell or in a pooled population.