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Frontiers in Cell and Developmental... 2022
PubMed: 35557953
DOI: 10.3389/fcell.2022.909619 -
Genome Research Aug 2021development begins with single-cell starvation and ends with multicellular fruiting bodies. Developmental morphogenesis is accompanied by sweeping transcriptional...
development begins with single-cell starvation and ends with multicellular fruiting bodies. Developmental morphogenesis is accompanied by sweeping transcriptional changes, encompassing nearly half of the 13,000 genes in the genome. We performed time-series RNA-sequencing analyses of the wild type and 20 mutants to explore the relationships between transcription and morphogenesis. These strains show developmental arrest at different stages, accelerated development, or atypical morphologies. Considering eight major morphological transitions, we identified 1371 milestone genes whose expression changes sharply between consecutive transitions. We also identified 1099 genes as members of 21 regulons, which are groups of genes that remain coordinately regulated despite the genetic, temporal, and developmental perturbations. The gene annotations in these groups validate known transitions and reveal new developmental events. For example, DNA replication genes are tightly coregulated with cell division genes, so they are expressed in mid-development although chromosomal DNA is not replicated. Our data set includes 486 transcriptional profiles that can help identify new relationships between transcription and development and improve gene annotations. We show its utility by showing that cycles of aggregation and disaggregation in allorecognition-defective mutants involve dedifferentiation. We also show sensitivity to genetic and developmental conditions in two commonly used actin genes, and , and robustness of the gene. Finally, we propose that is a better mRNA quantitation standard because it is less sensitive to external conditions than commonly used standards. The data set is available for democratized exploration through the web application dictyExpress and the data mining environment Orange.
Topics: Dictyostelium; Morphogenesis; RNA, Messenger; Regulon; Software
PubMed: 34183452
DOI: 10.1101/gr.275496.121 -
Frontiers in Cell and Developmental... 2022Mucolipidosis type IV, a devastating neurological lysosomal disease linked to mutations in the transient receptor potential channel mucolipin 1, TRPML1, a calcium...
Mucolipidosis type IV, a devastating neurological lysosomal disease linked to mutations in the transient receptor potential channel mucolipin 1, TRPML1, a calcium permeable channel in the membranes of vesicles in endolysosomal system. TRPML1 function is still being elucidated and a better understanding of the molecular pathogenesis of Mucolipidosis type IV, may facilitate development of potential treatments. We have created a model to study mucolipin function in the eukaryotic slime mould by altering expression of its single mucolipin homologue, . We show that in mucolipin overexpression contributes significantly to global chemotactic calcium responses in vegetative and differentiated cells. Knockdown of mucolipin also enhances calcium responses in vegetative cells but does not affect responses in 6-7 h developed cells, suggesting that in developed cells mucolipin may help regulate local calcium signals rather than global calcium waves. We found that both knocking down and overexpressing mucolipin often, but not always, presented the same phenotypes. Altering mucolipin expression levels caused an accumulation or increased acidification of Lysosensor Blue stained vesicles in vegetative cells. Nutrient uptake by phagocytosis and macropinocytosis were increased but growth rates were not, suggesting defects in catabolism. Both increasing and decreasing mucolipin expression caused the formation of smaller slugs and larger numbers of fruiting bodies during multicellular development, suggesting that mucolipin is involved in initiation of aggregation centers. The fruiting bodies that formed from these smaller aggregates had proportionately larger basal discs and thickened stalks, consistent with a regulatory role for mucolipin-dependent Ca signalling in the autophagic cell death pathways involved in stalk and basal disk differentiation in . Thus, we have provided evidence that mucolipin contributes to chemotactic calcium signalling and that is a useful model to study the molecular mechanisms involved in the cytopathogenesis of Mucolipidosis type IV.
PubMed: 35493081
DOI: 10.3389/fcell.2022.741967 -
Current Opinion in Biotechnology Oct 2022The identification of novel platform organisms for the production and discovery of small molecules is of high interest for the pharmaceutical industry. In particular,... (Review)
Review
The identification of novel platform organisms for the production and discovery of small molecules is of high interest for the pharmaceutical industry. In particular, the structural complexity of most natural products with therapeutic potential restricts an industrial production since chemical syntheses often require complex multistep routes. The amoeba Dictyostelium discoideum can be easily cultivated in bioreactors due to its planktonic growth behavior and contains numerous polyketide and terpene synthase genes with only a few compounds being already elucidated. Hence, the amoeba both bears a wealth of hidden natural products and allows for the development of new bioprocesses for existing pharmaceuticals. In this mini review, we present D. discoideum as a novel platform for the production of complex secondary metabolites and discuss its suitability for industrial processes. We also provide initial insights into future bioprocesses, both involving bacterial coculture setups and for the production of plant-based pharmaceuticals.
Topics: Amoeba; Bacteria; Biological Products; Dictyostelium; Pharmaceutical Preparations
PubMed: 35944344
DOI: 10.1016/j.copbio.2022.102766 -
Cells Jan 2022The incidence of neurological disorders is increasing due to population growth and extended life expectancy. Despite advances in the understanding of these disorders,... (Review)
Review
BACKGROUND
The incidence of neurological disorders is increasing due to population growth and extended life expectancy. Despite advances in the understanding of these disorders, curative strategies for treatment have not yet eventuated. In part, this is due to the complexities of the disorders and a lack of identification of their specific underlying pathologies. has provided a useful, simple model to aid in unraveling the complex pathological characteristics of neurological disorders including Alzheimer's disease, Parkinson's disease, Huntington's disease, neuronal ceroid lipofuscinoses and lissencephaly. In addition, has proven to be an innovative model for pharmaceutical research in the neurological field.
SCOPE OF REVIEW
This review describes the contributions of in the field of neurological research. The continued exploration of proteins implicated in neurological disorders in may elucidate their pathological roles and fast-track curative therapeutics.
Topics: Dictyostelium; Humans; Huntington Disease; Models, Biological; Neuronal Ceroid-Lipofuscinoses; Proteins
PubMed: 35159273
DOI: 10.3390/cells11030463 -
The International Journal of... 2020Simple organisms are preferred for understanding the molecular and cellular function(s) of complex processes. Dictyostelium discoideum is a lower eukaryote, a protist...
Simple organisms are preferred for understanding the molecular and cellular function(s) of complex processes. Dictyostelium discoideum is a lower eukaryote, a protist and a cellular slime mould, which has been in recent times used for various studies such as cell differentiation, development, cell death, stress responses etc. It is a soil amoeba (unicellular) that undertakes a remarkable, facultative shift to multicellularity when exposed to starvation and requires signal pathways that result in alteration of gene expression and finally show cell differentiation. The amoebae aggregate, differentiate and form fruiting bodies with two terminally differentiated cells: the dead stalk (non-viable) and dormant spores (viable). In India, starting from the isolation of Dictyostelium species to morphogenesis, cell signalling and social evolution has been studied with many more new research additions. Advances in molecular genetics make Dictyostelium an attractive model system to study cell biology, biochemistry, signal transduction and many more.
Topics: Animals; Biological Evolution; Biomedical Research; Cell Differentiation; Dictyostelium; Gene Expression Regulation; India; Models, Biological; Morphogenesis
PubMed: 32659023
DOI: 10.1387/ijdb.190208ss -
Frontiers in Cellular Neuroscience 2021The social amoeba is a model organism that is used to investigate many cellular processes including chemotaxis, cell motility, cell differentiation, and human disease... (Review)
Review
The social amoeba is a model organism that is used to investigate many cellular processes including chemotaxis, cell motility, cell differentiation, and human disease pathogenesis. While many single-cellular model systems lack homologs of human disease genes, genome encodes for many genes that are implicated in human diseases including neurodegenerative diseases. Due to its short doubling time along with the powerful genetic tools that enable rapid genetic screening, and the ease of creating knockout cell lines, is an attractive model organism for both interrogating the normal function of genes implicated in neurodegeneration and for determining pathogenic mechanisms that cause disease. Here we review the literature involving the use of to interrogate genes implicated in neurodegeneration and highlight key questions that can be addressed using as a model organism.
PubMed: 34776869
DOI: 10.3389/fncel.2021.759532 -
PLoS Biology Mar 2020Loners-individuals out of sync with a coordinated majority-occur frequently in nature. Are loners incidental byproducts of large-scale coordination attempts, or are they...
Loners-individuals out of sync with a coordinated majority-occur frequently in nature. Are loners incidental byproducts of large-scale coordination attempts, or are they part of a mosaic of life-history strategies? Here, we provide empirical evidence of naturally occurring heritable variation in loner behavior in the model social amoeba Dictyostelium discoideum. We propose that Dictyostelium loners-cells that do not join the multicellular life stage-arise from a dynamic population-partitioning process, the result of each cell making a stochastic, signal-based decision. We find evidence that this imperfectly synchronized multicellular development is affected by both abiotic (environmental porosity) and biotic (signaling) factors. Finally, we predict theoretically that when a pair of strains differing in their partitioning behavior coaggregate, cross-signaling impacts slime-mold diversity across spatiotemporal scales. Our findings suggest that loners could be critical to understanding collective and social behaviors, multicellular development, and ecological dynamics in D. discoideum. More broadly, across taxa, imperfect coordination of collective behaviors might be adaptive by enabling diversification of life-history strategies.
Topics: Biological Evolution; Dictyostelium; Models, Biological; Quorum Sensing; Spatio-Temporal Analysis; Stochastic Processes
PubMed: 32191693
DOI: 10.1371/journal.pbio.3000642 -
Frontiers in Cell and Developmental... 2021Acute respiratory distress syndrome (ARDS) involves damage to lungs causing an influx of neutrophils from the blood into the lung airspaces, and the neutrophils causing... (Review)
Review
Acute respiratory distress syndrome (ARDS) involves damage to lungs causing an influx of neutrophils from the blood into the lung airspaces, and the neutrophils causing further damage, which attracts more neutrophils in a vicious cycle. There are ∼190,000 cases of ARDS per year in the US, and because of the lack of therapeutics, the mortality rate is ∼40%. Repelling neutrophils out of the lung airspaces, or simply preventing neutrophil entry, is a potential therapeutic. In this minireview, we discuss how our lab noticed that a protein called AprA secreted by growing cells functions as a repellent for cells, causing cells to move away from a source of AprA. We then found that AprA has structural similarity to a human secreted protein called dipeptidyl peptidase IV (DPPIV), and that DPPIV is a repellent for human neutrophils. In animal models of ARDS, inhalation of DPPIV or DPPIV mimetics blocks neutrophil influx into the lungs. To move DPPIV or DPPIV mimetics into the clinic, we need to know how this repulsion works to understand possible drug interactions and side effects. Combining biochemistry and genetics in to elucidate the AprA signal transduction pathway, followed by drug studies in human neutrophils to determine similarities and differences between neutrophil and chemorepulsion, will hopefully lead to the safe use of DPPIV or DPPIV mimetics in the clinic.
PubMed: 34350188
DOI: 10.3389/fcell.2021.710005 -
Mitochondrial DNA. Part B, Resources 2021is a member of dictyostelids, the unicellular eukaryotes with a unique life cycle, including a social cycle. Despite the high diversity of dictyostelids, only five...
is a member of dictyostelids, the unicellular eukaryotes with a unique life cycle, including a social cycle. Despite the high diversity of dictyostelids, only five species' complete mitochondrial genome sequences were reported. This study aimed to add the mitochondrial genome sequence to the list. The size of this genome is 58,627 bp, with 73.99% A/T, containing 62 genes located on one strand: 41 protein-coding genes, three ribosomal RNA genes, and 18 transfer RNA genes. The 41 protein-coding genes comprised 18 oxidative phosphorylation-related, 16 ribosomal, and seven hypothetical protein-coding genes. The and gene contained introns, similar to other species of . The phylogenetic tree built based on 34 protein sequences supported the monophyletic clade of and the dictyostelids' ancestor's position between the two dictyostelids orders: Dictyosteliales and Acytosteliales.
PubMed: 34746396
DOI: 10.1080/23802359.2021.1989332