Biology subjects

Walter, S.

Publications and source records attributed to Walter, S..

28 records · Page 2Linked to original sources

bioRxiv2022

Honey Bees Get Map Coordinates from the Dance

Honeybees (Apis mellifera carnica) communicate the rhumb line to a food source (its direction and distance from the hive) by means of a waggle dance. We ask whether bees recruited by the dance use it only as a flying instruction or also translate it into a location vector in a map-like memory, so that information about spatial relations of environmental cues informs their attempts to find the source. The flights of recruits captured on exiting the hive and released at distant sites were tracked by radar. The recruits performed first a straight flight in the direction of the rhumb line. However, the vector portions of their flights and the ensuing tortuous search portions were strongly and differentially affected by the release site. Searches were biased toward the true location of the food and away from the location specified by translating the rhumb line origin to the release site. We conclude that by following the dance a recruit gets two messages, a polar flying instruction (the rhumb line) and its conversion to Cartesian map coordinates.

animal behavior and cognition↗

bioRxiv2021

A yeast lysosomal biogenesis map uncovers the cargo spectrum of lysosomal protein targeting pathways

The lysosome is the major catabolic organelle and a key metabolic signaling center of the cell. Mutations in lysosomal proteins can have catastrophic effects, causing neurodegeneration, cancer, and age-related diseases. The vacuole is the lysosomal analog of Saccharomyces cerevisiae that harbors many conserved proteins. Vacuolar proteins reach their destination via the endosomal vacuolar protein sorting (VPS) pathway, via the alkaline phosphatase (ALP or AP-3) pathway, and via the cytosol-to-vacuole transport (CVT) pathway. While these pathways have been extensively studied, a systematic understanding of the cargo spectrum of each pathway is completely lacking. Here we combine quantitative proteomics of purified vacuoles with mutant analyses to generate the lysosomal biogenesis map. This dataset harbors information on the cargo-receptor relationship of virtually all vacuolar proteins. We map binding motifs of Vps10 and the AP-3 complex and identify a novel cargo of the CVT pathway under nutrient-rich conditions. Our data uncover how organelle purification and quantitative proteomics can uncover fundamental insights into organelle biogenesis.

cell biology↗

bioRxiv2021

Herpesviral induction of germline transcription factor DUX4 is critical for viral gene expression

DUX4 is a transcription factor and a master regulator of embryonic genome activation (EGA). During early embryogenesis, EGA is crucial for maternal to zygotic transition at the 8-cell stage in order to overcome silencing of genes and enable transcription from the zygotic genome. In adult somatic cells, DUX4 expression is largely silenced. Activation is likely pathogenic, and in adult muscle cells causes genetic disorder Facioscapulohumeral Muscular Dystrophy (FSHD). We identified activation of DUX4 expression upon lytic replication of the herpesviruses HSV-1, HCMV, EBV and KSHV, but not of adenoviruses, negative strand RNA viruses or positive strand RNA viruses. We demonstrate by RNA-Seq analysis that DUX4 expression upon herpesviral replication leads to the induction of hundreds of DUX4 target genes including germline-specific retroelements as well as several members of the TRIM, PRAMEF and ZSCAN protein families. Moreover, we show that DUX4 expression is a direct consequence of herpesviral infection. DUX4 can be stimulated by overexpression of HSV-1 immediate early proteins, indicating active induction of EGA genes by herpesviral infection. We further show that DUX4 expression is critical for driving HSV-1 gene expression. Our results show that viruses from alpha-, beta- and gamma-herpesvirus subfamilies induce DUX4 expression and downstream germline-specific genes and retroelements. We hypothesize that herpesviruses induce DUX4 expression in order to induce an early embryonic-like transcriptional program that prevents epigenetic silencing of the viral genome and facilitates herpesviral gene expression.

microbiology↗

bioRxiv2020

Let Me Make You Happy, And I'll Tell You How you look around: Using an Approach-Avoidance Task as an Embodied Mood Prime in a Free-Viewing Task

The embodied approach of human cognition suggests that concepts are deeply dependent upon and constrained by an agents physical bodys characteristics, such as performed body movements. In this study, we attempted to broaden previous research on emotional priming, investigating the interaction of emotions and visual exploration. We used the joystick-based approach-avoidance task to influence the emotional states of participants, and subsequently, we presented pictures of news web pages on a computer screen and measured participants eye movements. As a result, the number of fixations on images increased, the total dwell time increased, and the average saccade length from outside of the images towards the images decreased after the bodily congruent priming phase. The combination of these effects suggests increased attention to web pages image content after the participants performed bodily congruent actions in the priming phase. Thus, congruent bodily interaction with images in the priming phase fosters visual interaction in the subsequent exploration phase.

neuroscience↗

bioRxiv2020

Phosphorylation of the GARP Subunit Vps53 by Snf1 Leads to the Formation of a Golgi-Mitochondria Contact Site (GoMiCS) in Yeast

The canonical function of the Golgi-associated retrograde protein (GARP) complex is the tethering of transport carriers. GARP belongs to the complexes associated with tethering containing helical rods (CATCHR) family and is a hetero-tetrameric complex consisting of the subunits Vps51, Vps52, Vps53 and Vps54. How the activity of GARP is regulated and if it possesses other functions besides tethering remains largely unknown. Here we identify the GARP subunit Vps53 as a novel regulatory target of the S. cerevisiae AMP kinase (AMPK) homolog Snf1. We find that Vps53 is both an in vivo and in vitro target of Snf1 and show that phosphorylation depends on the nature and quantity of the available carbon source. Phosphorylation of Vps53 does not affect the canonical trafficking pathway, but results in altered mitochondrial dynamics and the formation of a previously unknown contact site between the Golgi apparatus and mitochondria, termed GoMiCS. Our results provide an example of a subunit of a CATCHR complex with a constitutive function in membrane trafficking and an inducible role in organelle contact site formation. We anticipate our results to be the starting point for the characterization of this novel contact site.

cell biology↗

bioRxiv2020

Uptake of endogenous serine is important to maintain sphingolipid homeostasis in Saccharomyces cerevisiae

Sphingolipids are abundant and essential molecules in eukaryotes that have crucial functions as signaling molecules and as membrane components. Sphingolipid biosynthesis starts in the endoplasmic reticulum with the condensation of serine and palmitoyl-CoA. Sphingolipid biosynthesis is highly regulated to maintain sphingolipid homeostasis. Even though, serine is an essential component of the sphingolipid biosynthesis pathway, its role in maintaining sphingolipid homeostasis has not been precisely studied. Here we show that serine uptake is an important factor for the regulation of sphingolipid biosynthesis in Saccharomyces cerevisiae. Using genetic experiments, we find the broad-specificity amino acid permease Gnp1 to be important for serine uptake. We confirm these results with serine uptake assays in gnp1{Delta} cells. We further show that uptake of exogenous serine by Gnp1 is important to maintain cellular serine levels and observe a specific connection between serine uptake and the first step of sphingolipid biosynthesis. Using mass spectrometry-based flux analysis, we further observed imported serine as the main source for de novo sphingolipid biosynthesis. Our results demonstrate that yeast cells preferentially use the uptake of exogenous serine to regulate sphingolipid biosynthesis. Our study can also be a starting point to analyze the role of serine uptake in mammalian sphingolipid metabolism. Author SummarySphingolipids (SPs) are membrane lipids globally required for eukaryotic life. In contrast to other lipid classes, SPs cannot be stored in the cell and therefore their levels have to be tightly regulated. Failure to maintain sphingolipid homeostasis can result in pathologies including neurodegeneration, childhood asthma and cancer. However, we are only starting to understand how SP biosynthesis is adjusted according to need. In this study, we use genetic and biochemical methods to show that the uptake of exogenous serine is necessary to maintain SP homeostasis in Saccharomyces cerevisiae. Serine is one of the precursors of long chain bases in cells, the first intermediate of SP metabolism. Our results suggest that the uptake of serine is directly coupled to SP biosynthesis at ER-plasma membrane contact sites. Overall, our study identifies serine uptake as a novel regulatory factor of SP homeostasis. While we use yeast as a discovery tool, these results also provide valuable insights into mammalian SP biology especially under pathological conditions.

genetics↗

bioRxiv2019

Low membrane fluidity triggers lipid phase separation and protein segregation in vivo

All living organisms adapt their membrane lipid composition in response to changes in their environment or diet. These conserved membrane-adaptive processes have been studied extensively. However, key concepts of membrane biology linked to regulation of lipid composition including homeoviscous adaptation maintaining stable levels of membrane fluidity, and gel-fluid phase separation resulting in domain formation, heavily rely upon in vitro studies with model membranes or lipid extracts. Using the bacterial model organisms Escherichia coli and Bacillus subtilis, we now show that inadequate in vivo membrane fluidity interferes with essential complex cellular processes including cytokinesis, envelope expansion, chromosome replication/segregation and maintenance of membrane potential. Furthermore, we demonstrate that very low membrane fluidity is indeed capable of triggering large-scale lipid phase separation and protein segregation in intact, protein-crowded membranes of living cells; a process that coincides with the minimal level of fluidity capable of supporting growth. Importantly, the in vivo lipid phase separation is not associated with a breakdown of the membrane diffusion barrier function, thus explaining why the phase-separation process induced by low fluidity is biologically reversible.

microbiology↗

bioRxiv2019

Independent origin of MIRNA genes controlling homologous target genes by partial inverted duplication of antisense-transcribed sequences

Some microRNAs (miRNAs) are key regulators of developmental processes, mainly by controlling the accumulation of transcripts encoding transcription factors that are important for morphogenesis. MADS-box genes encode a family of transcription factors which control diverse developmental processes in flowering plants. Here we study the convergent evolution of two MIRNA (MIR) gene families, named MIR444 and MIR824, targeting members of the same clade of MIKCC-group MADS-box genes. We show that these two MIR genes most likely originated independently in monocots (MIR444) and in Brassicales (eudicots, MIR824). We provide evidence that in both cases the future target gene was transcribed in antisense prior to the evolution of the MIR genes. Both MIR genes then likely originated by a partial inverted duplication of their target genes, resulting in natural antisense organization of the newly evolved MIR gene and its target gene at birth. We thus propose a new model for the origin of MIR genes, MEPIDAS (MicroRNA Evolution by Partial Inverted Duplication of Antisense-transcribed Sequences). MEPIDAS is a refinement of the inverted duplication hypothesis. According to MEPIDAS, a MIR gene evolves at a genomic locus at which the future target gene is also transcribed in the antisense direction. A partial inverted duplication at this locus causes the antisense transcript to fold into a stem-loop structure that is recognized by the miRNA biogenesis machinery to produce a miRNA that regulates the gene at this locus. Our analyses exemplify how to elucidate the origin of conserved miRNAs by comparative genomics and will guide future studies.

evolutionary biology↗

bioRxiv2019

Genetic risk score for Alzheimer's disease is associated with poor hearing

IntroductionIncipient dementia or shared genetics may partly explain the association between hearing loss and dementia. We evaluated whether genetic variants known to increase Alzheimers disease (AD) also influence hearing difficulty. MethodsUK Biobank participants aged 56+ with Caucasian genetic ancestry self-reported difficulty hearing and hearing with background noise (n=244,915) and underwent objectively measured hearing assessments (n=80,074). Poor objective hearing was defined as >-5.5 dB speech reception threshold on a Digit Triplet Test. We evaluated whether an AD genetic risk score (AD-GRS; range -1.2 to 1.9), the weighted sum of 23 previously identified AD-related polymorphisms, predicted objective or self-reported poor hearing, using age, sex, and genetic ancestry adjusted logistic regression models. ResultsHigher AD-GRS predicted objectively measured poor hearing (OR=1.06; 95% CI: 1.01, 1.11) and self-reported problems hearing with background noise (OR=1.03; 95% CI: 1.00, 1.05). DiscussionUsing novel methods, we found evidence that AD genetic risk influences hearing loss.

epidemiology↗

bioRxiv2017

The GENIUS Approach to Robust Mendelian Randomization Inference

Mendelian randomization (MR) is a popular instrumental variable (IV) approach, in which one or several genetic markers serve as IVs that can be leveraged to recover under certain conditions, valid inferences about a given exposure-outcome causal association subject to unmeasured confounding. A key IV identification condition known as the exclusion restriction states that the IV has no direct effect on the outcome that is not mediated by the exposure in view. In MR studies, such an assumption requires an unrealistic level of knowledge and understanding of the mechanism by which the genetic markers causally affect the outcome, particularly when a large number of genetic variants are considered as IVs. As a result, possible violation of the exclusion restriction can seldom be ruled out in such MR studies, and if present, such violation can invalidate IVbased inferences even if unbeknownst to the analyst, confounding is either negligible or absent. To address this concern, we introduce a new class of IV estimators which are robust to violation of the exclusion restriction under a large collection of data generating mechanisms consistent with parametric models commonly assumed in the MR literature. Our approach which we have named \"MR G-Estimation under No Interaction with Unmeasured Selection\" (MR GENIUS) may in fact be viewed as a modification to Robins G-estimation approach that is robust to both additive unmeasured confounding and violation of the exclusion restriction assumption. We also establish that estimation with MR GENIUS may also be viewed as a robust generalization of the well-known Lewbel estimator for a triangular system of structural equations with endogeneity. Specifically, we show that unlike Lewbel estimation, MR GENIUS is under fairly weak conditions also robust to unmeasured confounding of the effects of the genetic IVs on both the exposure and the outcome, another possible violation of a key IV Identification condition. Furthermore, while Lewbel estimation involves specification of linear models both for the outcome and the exposure, MR GENIUS generally does not require specification of a structural model for the direct effect of invalid IVs on the outcome, therefore allowing the latter model to be unrestricted. Finally, unlike Lewbel estimation, MR GENIUS is shown to equally apply for binary, discrete or continuous exposure and outcome variables and can be used under prospective sampling, or retrospective sampling such as in a case-control study, as well as for right censored time-to-event outcomes under an additive hazards model.

epidemiology↗