Biology subjects

Rice, M. C.

Publications and source records attributed to Rice, M. C..

4 recordsLinked to original sources

bioRxiv2023

Microbe transmission from pet shop to lab-reared zebrafish reveals a pathogenic birnavirus

Zebrafish are popular research organisms selected for laboratory use due in part to widespread availability from the pet trade. Many contemporary colonies of laboratory zebrafish are maintained in aquaculture facilities that monitor and aim to curb infections that can negatively affect colony health and confound experiments. The impact of laboratory control on the microbial constituents associated with zebrafish in research environments compared to the pet trade are unclear. Diseases of unknown causes are common in both environments. We conducted a metagenomic survey to broadly compare the zebrafish-associated microbes in pet trade and laboratory environments. We detected many microbes in animals from the pet trade that were not found in laboratory animals. Co-housing experiments revealed several transmissible microbes including a newly described non-enveloped, double-stranded RNA virus in the Birnaviridae family we name Rocky Mountain birnavirus (RMBV). Infections were detected in asymptomatic animals from the pet trade, but when transmitted to laboratory animals RMBV was associated with pronounced antiviral responses and hemorrhagic disease. These experiments highlight the pet trade as a distinct source of diverse microbes that associate with zebrafish and establish a paradigm for the discovery of newly described pathogenic viruses and other infectious microbes that can be developed for study in the laboratory.

microbiology↗

bioRxiv2023

The Human Mitochondrial Genome Encodes for an Interferon-Responsive Host Defense Peptide

The mitochondrial DNA (mtDNA) can trigger immune responses and directly entrap pathogens, but it is not known to encode for active immune factors. The immune system is traditionally thought to be exclusively nuclear-encoded. Here, we report the identification of a mitochondrial-encoded host defense peptide (HDP) that presumably derives from the primordial proto-mitochondrial bacteria. We demonstrate that MOTS-c (mitochondrial open reading frame from the twelve S rRNA type-c) is a mitochondrial-encoded amphipathic and cationic peptide with direct antibacterial and immunomodulatory functions, consistent with the peptide chemistry and functions of known HDPs. MOTS-c targeted E. coli and methicillin-resistant S. aureus (MRSA), in part, by targeting their membranes using its hydrophobic and cationic domains. In monocytes, IFN{gamma}, LPS, and differentiation signals each induced the expression of endogenous MOTS-c. Notably, MOTS-c translocated to the nucleus to regulate gene expression during monocyte differentiation and programmed them into macrophages with unique transcriptomic signatures related to antigen presentation and IFN signaling. MOTS-c-programmed macrophages exhibited enhanced bacterial clearance and shifted metabolism. Our findings support MOTS-c as a first-in-class mitochondrial-encoded HDP and indicates that our immune system is not only encoded by the nuclear genome, but also by the co-evolved mitochondrial genome.

immunology↗

bioRxiv2023

Gadusol is a maternally provided sunscreen that protects fish embryos from DNA damage

Ultraviolet radiation (UVR) and its deleterious effects on living cells selects for UVR-protective mechanisms. Organisms across the tree of life evolved a variety of natural sunscreens to prevent UVR-induced cellular damage and stress. However, in vertebrates, only melanin is known to act as a sunscreen. Here we demonstrate that gadusol, a transparent compound discovered over 40 years ago in fish eggs, is a maternally provided sunscreen required for survival of embryonic and larval zebrafish exposed to UVR. Mutating an enzyme involved in gadusol biosynthesis increases the formation of cyclobutane pyrimidine dimers, a hallmark of UVB-induced DNA damage. Compared to the contributions of melanin and the chorion, gadusol is the primary sunscreening mechanism in embryonic and larval fish. The gadusol biosynthetic pathway is retained in the vast majority of teleost genomes but is repeatedly lost in species whose young are no longer exposed to UVR. Our data demonstrate that gadusol is a maternally provided sunscreen that is critical for early-life survival in the most species-rich branch of the vertebrate phylogeny.

developmental biology↗

bioRxiv2019

Discovery of a prevalent picornavirus by visualizing zebrafish immune responses

The discovery of new viruses currently outpaces our capacity for experimental examination of infection biology. To better couple virus discovery with immunology, we genetically modified zebrafish to visually report on virus infections. After generating a strain that expresses green fluorescent protein (GFP) under an interferon-stimulated gene promoter, we repeatedly observed transgenic larvae spontaneously expressing GFP days after hatching. RNA sequencing of GFP-positive zebrafish revealed a picornavirus distantly related to known viruses. We detected this virus in publicly available sequencing data from seemingly asymptomatic zebrafish in research institutes world-wide. These data revealed widespread tissue tropism and identified the clonal CG2 strain as notably vulnerable to picornavirus infection. Infection induces the expression of numerous antiviral immune defense genes in zebrafish, an effect also evident in public data. Our study describes a prevalent picornavirus that infects zebrafish, and provides new strategies for simultaneously discovering viruses and their impact on vertebrate hosts.

immunology↗