Biology subjects

Moser, A.

Publications and source records attributed to Moser, A..

6 recordsLinked to original sources

bioRxiv2024

Genetic analysis of the X-linked Adrenoleukodystrophy ABCD1 gene in Drosophila uncovers a role in Peroxisomal dynamics

X-linked adrenoleukodystrophy (X-ALD) is a progressive neurodegenerative disorder caused by a loss-of-function (LOF) mutation in the ATP-binding cassette subfamily D member 1 (ABCD1) gene, leading to the accumulation of very long-chain fatty acids (VLCFAs). This disorder exhibits striking heterogeneity; some male patients develop an early childhood neuroinflammatory demyelination disorder, while other patients, including adult males and most affected female carriers, experience a chronic progressive myelopathy. Adrenocortical failure is observed in almost all male patients, with age of onset varying sometimes being the first diagnostic finding. The gene underlying this spectrum of disease encodes an ATP-binding cassette (ABC) transporter that localizes to peroxisomes and facilitates VLCFA transport. X-ALD is considered a single peroxisomal component defect and does not play a direct role in peroxisome assembly. Drosophila models of other peroxisomal genes have provided mechanistic insight into some of the neurodegenerative mechanisms with reduced lifespan, retinal degeneration, and VLCFA accumulation. Here, we perform a genetic analysis of the fly ABCD1 ortholog Abcd1 (CG2316). Knockdown or deficiency of Abcd1 leads to VLCFA accumulation, salivary gland defects, locomotor impairment and retinal lipid abnormalities. Interestingly, there is also evidence of reduced peroxisomal numbers. Flies overexpressing the human cDNA for ABCD1 display a wing crumpling phenotype characteristic of the pex2 loss-of-function. Surprisingly, overexpression of human ABCD1 appears to inhibit or overwhelm peroxisomal biogenesis to levels similar to null mutations in fly pex2, pex16 and pex3. Drosophila Abcd1 is therefore implicated in peroxisomal number, and overexpression of the human ABCD1 gene acts a potent inhibitor of peroxisomal biogenesis in flies.

genetics↗

bioRxiv2023

Pancreatic islet cell stress induced by insulin-degrading enzyme deficiency promotes islet regeneration and protection from autoimmune diabetes

Appropriate tuning of protein homeostasis through mobilization of the unfolded protein response (UPR) is key to the capacity of pancreatic beta cells to cope with highly variable demand for insulin synthesis. An efficient UPR ensures a sufficient beta cell mass and secretory output but can also affect beta cell resilience to autoimmune aggression. The factors regulating protein homeostasis in the face of metabolic and immune challenges are insufficiently understood. We examined beta cell adaptation to stress in mice deficient for insulin-degrading enzyme (IDE), a ubiquitous protease with high affinity for insulin and genetic association with type 2 diabetes. IDE deficiency induced a low-level UPR in both C57BL/6 and autoimmune non-obese diabetic (NOD) mice, associated with rapamycin-sensitive beta cell proliferation strongly enhanced by proteotoxic stress. Moreover, in NOD mice, IDE deficiency protected from spontaneous diabetes and triggered an additional independent pathway, conditional on the presence of islet inflammation but inhibited by proteotoxic stress, highlighted by strong upregulation of regenerating islet-derived protein 2, a protein attenuating autoimmune inflammation. Our findings establish a key role of IDE in islet cell protein homeostasis, identify a link between low-level UPR and proliferation, and reveal an UPR-independent anti-inflammatory islet cell response uncovered in the absence of IDE of potential interest in autoimmune diabetes.

cell biology↗

bioRxiv2020

Seagrass beds provide habitat for crabs, shrimps and fish in two estuaries on the South Island of New Zealand

O_LISeagrasses are marine angiosperms that potentially provide habitat for crabs, shrimps and fish. However, these types of data are lacking for the seagrass species (Zostera muelleri/rimur[e]hia) that inhabit intertidal estuaries on the South Island of New Zealand. C_LIO_LIAbundances of crabs, shrimps and fish were therefore quantified from 361 non-destructive seine tows done in seagrass beds and bare mudflats in Duvauchelle bay and two sites in the Avon-Heathcote/Ihutai estuary between October 2019 and February 2020. C_LIO_LIA total of 2549 crabs, 5824 shrimps and 1149 fish (75% were juvenile flounders) were identified and counted in the seine-net and immediately released back in healthy condition to the exact location from where they were caught. C_LIO_LIOnly few seagrass leaves were caught in the net and these leaves may have been previously uprooted drift fragments. The instant catch-and-release methodology therefore leaves, literally, nothing but a footprint. C_LIO_LIMore fish taxa, including two species of pipefish, were found in seagrass beds in Duvauchelle bay than in the Avon-Heathcote estuary. Fish (minus juvenile flounders) were also more abundant in these seagrass beds. Furthermore, juvenile flounders and shrimps were more abundant in Duvauchelle bay compared to the Avon-Heathcote estuary, but were found in similar abundances in seagrass beds and on bare flats. C_LIO_LIIt is possible that more fish were found in Duvauchelle seagrass beds because these beds have adjacent deeper areas, and may have high connectivity to seagrass beds in nearby bays. This hypothesis should be tested by sampling more seagrass beds in different types of estuaries and bays. C_LIO_LIBy contrast, crabs were more abundant in the Avon-Heathcote estuary, where spider crabs were most abundant in the seagrass beds, but other crabs were found in similar abundances in seagrass beds and bare habitat. We hypothesize that crab abundances were higher in the Avon-Heathcote estuary because of lower fish predation pressure and/or larger populations of prey like mollusc and polychaetes. C_LIO_LIOur results suggests that (a) superficially similar Zostera beds in relatively close proximity can provide very different habitat values for fish and crustaceans, (b) seagrass beds with higher diversity and abundances of fish may be prioritized in conservation and management (assuming other important ecosystem functions are similar between beds), and (c) that pipefish may be useful indicator organisms, representing healthy, extensive, dense and connected seagrass beds. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=177 SRC="FIGDIR/small/120055v1_ufig1.gif" ALT="Figure 1"> View larger version (111K): org.highwire.dtl.DTLVardef@1c21731org.highwire.dtl.DTLVardef@180c521org.highwire.dtl.DTLVardef@10e2875org.highwire.dtl.DTLVardef@824c21_HPS_FORMAT_FIGEXP M_FIG C_FIG

ecology↗

bioRxiv2018

Long read-based de novo assembly of low complex metagenome samples results in finished genomes and reveals insights into strain diversity and an active phage system

BackgroundComplete and contiguous genome assemblies greatly improve the quality of subsequent systems-wide functional profiling studies and the ability to gain novel biological insights. While a de novo genome assembly of an isolated bacterial strain is in most cases straightforward, more informative data about co-existing bacteria as well as synergistic and antagonistic effects can be obtained from a direct analysis of microbial communities. However, the complexity of metagenomic samples represents a major challenge. While third generation sequencing technologies have been suggested to enable finished metagenome-assembled-genomes, to our knowledge, the complete genome assembly of all dominant strains in a microbiome sample has not been shown so far. Natural whey starter cultures (NWCs) are used in the production of cheese and represent low complex microbiomes. Previous studies of Swiss Gruyere and selected Italian hard cheeses, mostly based on amplicon-based metagenomics, concurred that three species generally pre-dominate: Streptococcus thermophilus, Lactobacillus helveticus and Lactobacillus delbrueckii.\n\nResultsTwo NWCs from Swiss Gruyere producers were subjected to whole metagenome shotgun sequencing using Pacific Biosciences Sequel, Oxford Nanopore Technologies MinION and Illumina MiSeq platforms. We achieved the complete assembly of all dominant bacterial genomes from these low complex NWCs, which was corroborated by a 16S rRNA based amplicon survey. Moreover, two distinct L. helveticus strains were successfully co-assembled from the same sample. Besides bacterial genomes, we could also assemble several bacterial plasmids as well as phages and a corresponding prophage. Biologically relevant insights could be uncovered by linking the plasmids and phages to their respective host genomes using DNA methylation motifs on the plasmids and by matching prokaryotic CRISPR spacers with the corresponding protospacers on the phages. These results could only be achieved by employing third generation, long-read sequencing data able to span intragenomic as well as intergenomic repeats.\n\nConclusionsHere, we demonstrate the feasibility of complete de novo genome assembly of all dominant strains from low complex NWCs based on whole metagenomics shotgun sequencing data. This allowed to gain novel biological insights and is a fundamental basis for subsequent systems-wide omic analyses, functional profiling and phenotype to genotype analysis of specific microbial communities.

genomics↗

bioRxiv2018

Building a local community of practice in scientific programming for Life Scientists

For most experimental biologists, handling the avalanche of data generated is similar to learning how to drive on your own. Although that might be doable, it is preferable and safer to learn programming and good practices together and preferably from experienced scientists. One way to achieve this is to build local communities of practice in scientific programming by bringing together life scientists that perform code-intensive research to spread know-how and good practices. The community will make sure that, for a given researcher working for an academic institution, their capacity to conduct data-intensive research will not be arbitrarily reliant on the presence of well-trained bioinformaticians in their vicinity.\n\nIn this paper, we propose a three-step field guide for building a local community of practice in scientific programming for life scientists. The first step is organizing a Carpentries programming workshop designed for researchers new to computational biology. However, while such workshops provide an immediate solution for learning, more regular long-term assistance is also needed. Researchers need persisting, local support to continue learning and solving programming issues that may hamper their research progress. The solution we describe here is to implement a Mozilla Study Group where researchers can meet-up and help each other in a \"safe-learning atmosphere\". We describe two real-life examples of building local communities of practice: one in the Netherlands at the Amsterdam Science Park and one in the United States at the University of Wisconsin-Madison. In order to help future researchers to build their own community of practice in scientific programming we discuss challenges and implemented solutions.\n\nWe believe that our local communities of practice will prove useful for other life scien-tists who want to set up similar support groups for researchers involved in scientific programming and data science.\n\nAuthor summaryIn this paper, we describe why and how to build a community of practice for life scientists that start to make more use of computers and programming in their research. A community of practice is a small group of scientists that meet regularly to help each other and promote good practices in scientific computing. While most life scientists are well-trained in the laboratory to conduct experiments, good practices with (big) datasets and their analysis are often missing. This paper proposes a field-guide on how to build such a community of practice at a local academic institution. Based on two real-life examples, challenges and related recommendations are provided. We believe that the current data deluge that life scientists will increasingly face can benefit from the implementation of these small communities. Good practices spread among experimental scientists will foster open, transparent, sound scientific results beneficial to society.

scientific communication and education↗

bioRxiv2017

Hemimetabolous genomes reveal molecular basis of termite eusociality

Around 150 million years ago, eusocial termites evolved from within the cockroaches, 50 million years before eusocial Hymenoptera, such as bees and ants, appeared. Here, we report the first, 2GB genome of a cockroach, Blattella germanica, and the 1.3GB genome of the drywood termite, Cryptotermes secundus. We show evolutionary signatures of termite eusociality by comparing the genomes and transcriptomes of three termites and the cockroach against the background of 16 other eusocial and non-eusocial insects. Dramatic adaptive changes in genes underlying the production and perception of pheromones confirm the importance of chemical communication in the termites. These are accompanied by major changes in gene regulation and the molecular evolution of caste determination. Many of these results parallel molecular mechanisms of eusocial evolution in Hymenoptera. However, the specific solutions are remarkably different, thus revealing a striking case of convergence in one of the major evolutionary transitions in biological complexity.

evolutionary biology↗