• Wed. Feb 21st, 2024

Novel genetic screen provides clues as to how

Novel genetic screen provides clues as to how

Figure: Transmission electron microscopy image of Toxoplasma gondii
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Credit: Masahiro Yamamoto

OSAKA, Japan – Although the presence of harmful organisms in your home can be solved by calling an exterminator, it can be very difficult to get rid of harmful parasites in the body. A single-celled parasite known as Toxoplasma gondii (Henceforth Toxoplasma) commonly infects humans and other animals, and the resulting condition, known as toxoplasmosis, can cause serious health problems in people with weakened immune systems. Recently, researchers in Japan have developed a tool to investigate how Toxoplasma Toxoplasmosis promotes its survival within a host, shedding new light on possibilities for treatment and prevention.

In a new study published in Cell reportsOsaka University researchers conducted a genetic screen in mice using CRISPR technology to confirm known genes and identify new genes involved. Toxoplasma Fitness, i.e., the ability of the parasite to survive and grow within a host. CRISPR genome editing is a method that uses small pieces of genetic material known as guide RNA (gRNA) to modify specific sequences of DNA in the genome.

CRISPR screens, which use several gRNAs to systematically modify target genes in an organism, can be used to infer which genes are involved in a particular biological process. The research team aims to use a CRISPR screen ToxoplasmaInfected mice recognize virulence factors, which are helpful traits Toxoplasma Avoid the host immune system. When virus components are involved Toxoplasma Previously identified in hosts with healthy immune systems, these factors have not been fully explored in hosts with compromised immune systems.

“when Toxoplasma When infection occurs, the host’s immune system responds by producing a protein called interferon-γ (IFN-γ), which stimulates other molecules to help prevent it. Toxoplasma from multiplying,” explains senior author Masahiro Yamamoto. “We performed the CRISPR screen in healthy mice and immunocompromised mice lacking the receptor for IFN-γ, which allowed us to assess the effects of host genetics and parasite genetics on immune-related virulence factors.”

Researchers infected mice Toxoplasma; these Toxoplasma Contains gRNA libraries that affect certain genes of interest. Later, the group was taken out Toxoplasma Gene expression of the parasite was assessed in mice. This analysis allowed the research team to identify which genes were promoted Toxoplasma fitness, and facilitated comparison of gene expression between healthy and immunocompromised mice.

“Our highly reproducible, in vivo screen identified both IFN-γ-dependent and IFN-γ-independent fitness genes. Toxoplasma viruses,” says lead author Yuta Tachibana. “We have successfully identified several virus components Toxoplasma.”

These genes represent potential targets for treatment and prevention Toxoplasma infection Also, the research team’s in vivo method Genetic testing can provide the basis for developing new treatments and vaccines for toxoplasmosis.

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Published article “Host genetics, IFN-γ-dependent Toxoplasma genes encoding in vivo CRISPR screens highlighting secreted and non-secreted virulence factors”. Cell reports In DOI: https://doi.org/10.1016/j.celrep.2023.112592

About Osaka University

Established in 1931 as one of Japan’s seven imperial universities, Osaka University is now one of Japan’s leading comprehensive universities with a broad disciplinary spectrum. Associated with this power is a unified drive for innovation that extends throughout the scientific process, from basic research to the creation of practical technology with positive economic consequences. Its commitment to innovation is recognized in Japan and around the world, being named Japan’s most innovative university in 2015 (Reuters 2015 Top 100) and one of the world’s most innovative institutions in 2017 (Innovative Universities and Nature Index Innovation 2017). Now, Osaka University contributes to innovation for human well-being, sustainable development of society, and social transformation as a designated National University Corporation selected by the Ministry of Education, Culture, Sports, and Science and Technology.

Website: https://resou.osaka-u.ac.jp/en


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