The present disclosure provides a method for genetic analysis of gene variants as well as a system for implementing such analysis.

The present invention relates to a Drosophila in vitro system which was used to demonstrate that dsRNA is processed to RNA segments 21-23 nucleotides (nt) in length. Furthermore, when these 21-23 nt fragments are purified and added back to Drosophila extracts, they mediate RNA interference in the absence of long dsRNA. Thus, these 21-23 nt fragments are the sequence-specific mediators of RNA degradation. A molecular signal, which may be their specific length, must be present in these 21-23 nt fragments to recruit cellular factors involved in RNAi. This present invention encompasses these 21-23 nt fragments and their use for specifically inactivating gene function. The use of these fragments (or chemically synthesized oligonucleotides of the same or similar nature) enables the targeting of specific mRNAs for degradation in mammalian cells, where the use of long dsRNAs to elicit RNAi is usually not practical, presumably because of the deleterious effects of the interferon response. This specific targeting of a particular gene function is useful in functional genomic and therapeutic applications.

The invention relates, in part, to methods to design and construct gene drives such as daisy chain gene drives, suppression gene drives, and other types of gene drives that may be included in cell lines and organisms.

The present invention relates to: a transgenic Caenorhabditis elegans in which a glutamine tRNA 5 terminus-derived fragment (Gln 5-tsRNA) is overexpressed; a preparation method therefor; and a method for screening for aging-associated factors by using the transgenic Caenorhabditis elegans. A transgenic Caenorhabditis elegans model provided in the present invention is an animal model in which Gln 5-tsRNA is overexpressed such that aging is inhibited. When the model of the present invention is used, anti-aging mechanisms can be easily investigated, thereby significantly contributing to various research fields such as that of developing new anti-aging drugs and screening for age-inducing materials.

Provided herein are devices, systems and methods for separating age and size matched nematodes from a mixed size population of nematodes and/or debris. The device and system use a filter membrane with a defined pore size located between an upper housing with a first chamber adapted to receive a liquid sample comprising the mixed size population nematodes and a lower housing with a second chamber. Use of the system, along with a sample vessel, provide the user a method for efficiently and effectively isolating an age and size synchronized population of nematodes.

Inappropriate activation of innate immune responses in nematode intestinal epithelial cells underlies the pathophysiology of some inflammatory disorders. Immunostimulatory xenobiotics are known to protect nematodes from bacterial infection (e.g., Pseudomonas aeruginosa). Conversely, these same xenobiotics are toxic to uninfected nematodes. These xenobiotics were subjected to a forward genetic screen in uninfected nematodes to identify nematode mutants that were resistant to the deleterious effects of these xenobiotics. These resistant nematode strains contained hypomorphic mutations in each of the known components of the p38 MAP kinase cassette (tir-1, nsy-1, sek-1 and pmk-1), demonstrating that hyperstimulation of p38 MAPK innate immune responses may be responsible for the induced toxicity. A second genetic screen using dominant activators of the p38 MAPK pathway identified a single allele that had a gain-of-function (gf) mutation in nsy-1, the MAP kinase kinase kinase that acts upstream of p38 MAPK pmk-1.

The present disclosure generally relates to genetic methods of manipulating helminths, e.g., hookworms, to act as a biological delivery vehicle for therapeutic polypeptides in mammals. Furthermore, the disclosure is drawn to compositions comprising genetically modified hookworms and methods of use, including the administration of the helminths to one or more mammals to provide a continuous supply of a synthetic or modified polypeptide (e.g., HIV neutralizing antibodies) which may mitigate infection and/or infection intensity, otherwise resulting in an increase in a desirable phenotypic trait.

The disclosed subject matter provides a system and methods for automated imaging and manipulation of small animals. In exemplary embodiments, the disclosed subject matter provides a motorized picking assembly, that is coupled to a processor and adapted to remove selected small animals from a source plate and transfer them to a destination plate. The disclosed subject matter provides methods, which include identifying at least one parameter for the small organisms, selecting organisms based on the parameter and transferring selected organisms from the source plate to the destination plate. In certain embodiments, the disclosed subject matter provides a handheld self-sterilizing loop tool for the manual manipulation of small organisms.

Systems and methods relate to transgenic organisms and their use as biosensors are described. In some embodiments, the systems and methods include a first population of transgenic organisms that includes a first constitutively expressed reporter gene, and a first transgene that includes a first inducible promoter from a response pathway gene, wherein the first inducible promoter is coupled to a first reporter gene. Other embodiments are described.

Among the various aspects of the present disclosure is the provision of transgenic hookworm compositions and systems and methods of use thereof. The present teachings include compositions for a transgenic hookworm that treats a disease, condition, or indication. Also disclosed is a personal protective biosystem based on the transgenic hookworm, and methods to treat a disease, condition, or indication of a subject using transgenic hookworm compositions.