This invention relates to the use of CRISPR nucleic acids to screen for essential and non-essential genes and expendable genomic islands in bacteria, archaea, algae and/or yeast, to kill bacteria, archaea, algae and/or yeast, to identify the phenotype of a gene or genes, and/or to screen for reduced genome size and/or a gene deletion in bacteria, archaea, algae and/or yeast.

Embodiments of the present disclosure relate generally to the genetic analysis of intractable microbes. More particularly, the present disclosure provides materials and methods that incorporate chemical mutagenesis, phenotypic selection, suppression analysis, and genomic sequencing-based mutational mapping, to identify novel genetic regulators in previously intractable organisms, such as microbes that constitute the human microbiome. Given the paucity of experimental tools to manipulate bacterial genomes, there is a need for improved methods for determining how microbial communities assemble and influence human and environmental health.

Methods, compositions, and kits are provided for CRISPR/Cas mediated transcriptional modulation.

The invention provides compositions and methods for performing mammalian cell genetics, e.g., genetic screens, using near-haploid cells. The invention further provides genes and gene products isolated using the inventive methods and methods of use thereof.

A HTP genomic engineering platform for improving filamentous fungal cells that is computationally driven and integrates molecular biology, automation, and advanced machine learning protocols is provided. This integrative platform utilizes a suite of HTP molecular tool sets to create HTP genetic design libraries, which are derived from, inter alia, scientific insight and iterative pattern recognition. Methods for isolating clonal populations derived from individual fungal spores are also provided.

Disclosed are yeast cells expressing TAR DNA-binding protein 43 (TDP-43) and methods of screening yeast cells to identify compounds that prevent or suppress TDP-43-induced toxicity, compounds that inhibit the formation or maintenance of cytoplasmic inclusions of TDP-43, genetic suppressors or enhancers of TDP-43-induced toxicity, and genetic suppressors or enhancers of the formation or maintenance of cytoplasmic inclusions of TDP-43. Compounds identified by such screens can be used to treat or prevent TDP-43 proteinopathies such as frontotemporal lobar degeneration or amyotrophic lateral sclerosis.

The disclosure provides for screening methodologies using gene fragment overexpression that provide for the identification of peptide sequences which can modulate the functional regions of proteins of interests, and uses thereof. The disclosure further relates to peptide, polypeptide and polynucleotide identified by the methods of the disclosure, compositions containing such peptide, polypeptide and polynucleotides and uses thereof.

The invention encompasses compositions, kits and methods for modifying bacteria, preferably naturally occurring bacteria, in situ. These can be used to treat, prevent or cure microbiome-associated diseases or disorders by modulating the molecules expressed and/or secreted by bacterial populations of the microbiome in a specific manner. The genomic modifications can modify the interactions between part or all of these populations and the host in a way that decreases their deleterious potential on host health. The compositions, kits and methods of the invention do not result in the direct death of these populations or a direct significant inhibition of their growth. The invention further includes methods for screening for genetic modifications in the bacteria, for determining the efficiency of vectors at inducing these genetic mutations, and for determining the effects of these mutations on bacterial growth.

The present invention relates to methods associated with metagenomic screening for metabolite induced elements (MIEs) and the subsequent use of the MIEs in screening metagenomic libraries to identify metabolic pathways and pathway components in one or more partial or complete operons. In one aspect the method may be an iterative approach to metagenomic screening which involves substrate and product selection.

The present disclosure relates to methods for performing arrayed nucleic acid-guided nuclease nickase fusion editing allowing for rapid genotypic/phenotypic correlation without sequencing.