Provided herein are genetically modified cells and methods of their production, wherein such methods include introducing a nucleic acid molecule including a plurality of index sequences into a cell comprising a synthetic landing pad, wherein each of the plurality of index sequences includes a first portion of a sequence and the synthetic landing pad includes a second portion of the sequence. The method further includes generating a plurality of cells that include the synthetic landing pad and the nucleic acid molecule including the plurality of index sequences and integrating one of the plurality of index sequences into the synthetic landing pad in each of the cells, thereby linking the first and second portions of the sequence. The linked first and second portions of the sequence result in a functional gene and cells including the integrated index sequence are selected based on presence or activity of the functional gene.

Disclosed are methods, compositions, and systems for transforming silkworms to produce spider silk and analogs of spider silk. In certain embodiments, the method may include inserting a DNA sequence coding for at least a portion of a spider silk fibroin polypeptide, or an analog of a spider silk fibroin polypeptide, positioned between at least a portion of the 5 and 3 ends of a silkworm fibroin gene to generate a fusion gene construct having a sequence that encodes for a polypeptide comprising both spider silk fibroin and silkworm silk fibroin sequences. In certain embodiments, the fused gene is able to replace a native gene present in the silkworm such that the transformed silkworm expresses a polypeptide comprising a spider silk fibroin polypeptide, or an analog thereof, and expresses significantly less of the native silkworm silk.

The present disclosure provides transgenic nematode systems for assessing function of heterologous genes, their variants and drug discovery. The transgenic nematodes contain a heterologous gene that is inserted via homologous recombination at the native locus replacing and removing the nematode ortholog, wherein expression of the heterologous gene rescues function of the removed nematode ortholog and a transgenic control animal is provided. The heterologous gene may be further modified to provide a variant, such as a human clinical variant, whereby a transgenic test animal is provided. Those transgenic test animals are used in methods to assess function of the heterologous variant and drug screens to find therapeutic candidates reversing deviant activity back to wildtype.

The present disclosure provides transgenic nematode systems for assessing function of heterologous genes, their variants and drug discovery. The transgenic nematodes contain a heterologous gene that is inserted via homologous recombination at the native locus replacing and removing the nematode ortholog, wherein expression of the heterologous gene rescues function of the removed nematode ortholog and a transgenic control animal is provided. The heterologous gene may be further modified to provide a variant, such as a human clinical variant, whereby a transgenic test animal is provided. Those transgenic test animals are used in methods to assess function of the heterologous variant and drug screens to find therapeutic candidates reversing deviant activity back to wildtype.

Compositions and methods for modulation by upregulation (up modulation) and/or downregulation (down modulation) of mitophagy are described for the treatment of mitochondrial disorders including OPA-1 related disease and Single Large Scale Mitochondrial DNA Deletion (SLSMD). Also disclosed are a number of screening assays and gene targets having utility for the identification of agents which modulate the phenotype associated with such disorders.

The present invention relates to an animal model for oxidative stress research and use thereof, and more specifically, the present invention can utilize a mutant of RCAT having a regulatory function for an antioxidant stress regulator in Caenorhabditis elegans and a human cell line expressing RCAT as animal and human cell line models for oxidative stress research, using the mutant and the human cell line.

A method for evaluating biofilm formation on a medical device material in vivo using an invertebrate includes: a step of inserting the medical device material between a hypodermal portion and an intestinal tract of an invertebrate, a step of extracting the medical device material from the invertebrate, and a step of evaluating biofilm formation on the surface of the medical device material; the invertebrate is for use in this evaluation of the biofilm formation.