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Probes of abnormal worm development led to discovery of microRNAs and their role in gene expression.

Neurodegenerative diseases are characterized by distinct protein aggregates, such as those of α-synuclein and tau. Lysosomal defect is a key contributor to the accumulation and propagation of aberrant protein aggregates in these diseases. The discoveries of common proteinopathies in multiple forms of lysosomal storage diseases (LSDs) and the identification of some LSD genes as susceptible genes for those proteinopathies suggest causative links between LSDs and the proteinopathies. The present study hypothesized that defects in lysosomal genes will differentially affect the propagation of α-synuclein and tau proteins, thereby determining the progression of a specific proteinopathy. We established an imaging-based high-contents screening (HCS) system in Caenorhabditis elegans (C. elegans) model, by which the propagation of α-synuclein or tau is measured by fluorescence intensity. Using this system, we performed RNA interference (RNAi) screening to induce a wide range of lysosomal malfunction through knock down of 79 LSD genes, and to obtain the candidate genes with significant change in protein propagation. While some LSD genes commonly affected both α-synuclein and tau propagation, our study identified the distinct sets of LSD genes that differentially regulate the propagation of either α-synuclein or tau. The specificity and efficacy of these LSD genes were retained in the disease-related phenotypes, such as pharyngeal pumping behavior and life span. This study suggests that distinct lysosomal genes differentially regulate the propagation of α-synuclein and tau, and offer a steppingstone to understanding disease specificity. [BMB Reports 2023; 56(12): 657-662].

Neuronal differentiation is highly coordinated through a cascade of gene expression, mediated via interactions between transacting transcription factors and cis-regulatory elements of their target genes. However, the mechanisms of transcriptional regulation that determine neuronal cell-fate are not fully understood. Here, we show that the nuclear transcription factor Y (NF-Y) subunit, NFYA-1, is necessary and sufficient to express the flp-3 neuropeptide gene in the IL1 neurons of C. elegans. flp-3 expression is decreased in dorsal and lateral, but not ventral IL1s of nfya-1 mutants. The expression of another terminally differentiated gene, eat-4 vesicular glutamate transporter, is abolished, whereas the unc-8 DEG/ENaC gene and pan-neuronal genes are expressed normally in IL1s of nfya-1 mutants. nfya-1 is expressed in and acts in IL1s to regulate flp-3 and eat-4 expression. Ectopic expression of NFYA-1 drives the expression of flp-3 gene in other cell-types. Promoter analysis of IL1-expressed genes results in the identification of several cisregulatory motifs which are necessary for IL1 expression, including a putative CCAAT-box located in the flp-3 promoter that NFYA-1 directly interacts with. NFYA-1 and NFYA-2, together with NFYB-1 and NFYC-1, exhibit partly or fully redundant roles in the regulation of flp-3 or unc-8 expression, respectively. Taken together, our data indicate that the NF-Y complex regulates neuronal subtype-specification via regulating a set of terminal-differentiation genes. [BMB Reports 2023; 56(3): 153-159].

The article informs that scientists are preparing genome map of worm Caenorhabditis elegans and extracted cells from thousands of C. elegans larvae and chemically processed them in a way that assigned a unique "barcode" to each cell.

Endogenous retroviruses (ERVs) are retrotransposons present in various metazoan genomes and have been implicated in metazoan evolution as well as in nematodes and humans. The long terminal repeat (LTR) retrotransposons contain several regulatory sequences including promoters and enhancers that regulate endogenous gene expression and thereby control organismal development and response to environmental change. ERVs including the LTR retrotransposons constitute 8% of the human genome and less than 0.6% of the Caenorhabditis elegans (C. elegans) genome, a nematode genetic model system. To investigate the evolutionarily conserved mechanism behind the transcriptional activity of retrotransposons, we generated a transgenic worm model driving green fluorescent protein (GFP) expression using Human endogenous retroviruses (HERV)-K LTR as a promoter. The promoter activity of HERV-K LTR was robust and fluorescence was observed in various tissues throughout the developmental process. Interestingly, persistent GFP expression was specifically detected in the adult vulva muscle. Using deletion constructs, we found that the region from positions 675 to 868 containing the TATA box was necessary for promoter activity driving gene expression in the vulva. Interestingly, we found that the promoter activity of the LTR was dependent on che-1 transcription factor, a sensory neuron driver, and lin-15b, a negative regulator of RNAi and germline gene expression. These results suggest evolutionary conservation of the LTR retrotransposon activity in transcriptional regulation as well as the possibility of che-1 function in non-neuronal tissues. [BMB Reports 2020; 53(10): 521-526].

The article focuses on associate professor Ahna Skop of the University of Wisconsin in Madison, Wisconsin. It states that in 1992, when she was on her sophomore year studying ceramics and biology at the Syracuse University, she wanted to be a scientist. It mentions that Skop worked at the laboratory of worm biologist John White on how Caenorhabditis created their cleavage plane. It adds that in 2006, she received the Presidential Early Career Award for Scientists and Engineers (PECASE).

The article provides information on brain research initiatives and neuroscience projects to compute interaction of nerve cells inside human brain. Topics discussed include testing analytics proposed by Eric Jonas and Konrad Kording from neuroscience background, basic computing function, and research on Caenorhabditis elegans.

The article discusses the selfish genes sup-35 and pha-1 in nematode Caenorhabditis (C.) elegans, referencing research by geneticist Leonid Kruglyak. An overview of the sup-35 gene's use of a toxin to cause the death C. elegans offspring and eggs, including in regard to the role that a possible antidote gene could play in preventing this, is provided.

The article discusses research by Shi-Qing Cai of the Chinese Academy of Sciences in Shanghai, China, and colleagues, in the March 12, 2014 issue of the "Journal of Neuroscience." The team found that the roundworm Caenorhabditis elegans with a genetic mutation in the eat-2 gene, which made them inefficient eaters, continued to produce the neurotransmitters serotonin and dopamine and extended their life spans.

The article reports on the new research which identifies naturally occurring processes that allow many genes to slow aging and protect against cancer in Caenorhabditis elegans roundworm. It notes that many of the worm genes have counterparts in humans and it suggests that new drugs may be produced to fight cancer diseases through this discovery. The new research indicate that cellular changes leading to longevity counteract tumor cell growth.

Reports on a gene expression study of Caenorhabditis elegans. Comparison of worms with a mutated form of the daf-2 gene, associated with greater longevity, to wild-type worms; Use of serial analysis of gene expression (SAGE) libraries; Observation that the genes within the same families tended to be co-regulated together; Expression of the heterogeneous genes associated with metabolism at a lower level in midlife in the mutant worm.

Reports on the discovery of genes that were missed by previous genome analysis methods. Extension of an original computer program to the genome of the Caenorhabditis elegans nematode worm; Prediction of the existence of more genes; Predicted genes in WormBase, the standard public C. elegans annotation database; Adaptation and extension of the TWINSCAN genetic prediction algorithm.

Recognition of apoptotic cells by phagocytic cells in Caenorhabditis elegans has been something of a mystery. A secreted transthyretin-like protein, TTR-52, has been identified as a bridging molecule between apoptotic cells and CED-1 on the phagocytic cells that engulf them.

In Caernorhabditis elegans, homologue pairing is mediated by specialized regions near one end of each chromosome in conjunction with zinc finger (ZnF)-bearing proteins. Families of repeated sequences that are enriched within these regions have now been identified. By recruiting their cognate ZnF-bearing proteins, these regions promote pairing and synapsis.