Biology subjects

Davey, M.

Publications and source records attributed to Davey, M..

23 records · Page 2Linked to original sources

bioRxiv2021

Systematic analysis of membrane contact sites in Saccharomyces cerevisiae uncovers modulators of cellular lipid distribution

Actively maintained close appositions, or contact sites, between organelle membranes, enable the efficient transfer of biomolecules between the various cellular compartments. Several such sites have been described together with their tethering machinery. Despite these advances we are still far from a comprehensive understanding of the function and regulation of most contact sites. To systematically characterize the proteome of contact sites and support the discovery of new tethers and functional molecules, we established a high throughput screening approach in Saccharomyces cerevisiae based on co-localization imaging. We imaged split fluorescence reporters for six different contact sites, two of which have never been studied before, on the background of 1165 strains expressing a mCherry-tagged yeast protein that have a cellular punctate distribution (a hallmark of contact sites). By scoring both co-localization events and effects on reporter size and abundance, we discovered over 100 new potential contact site residents and effectors in yeast. Focusing on several of the newly identified residents, we identified one set of hits as previously unrecognized homologs to Vps13 and Atg2. These proteins share their lipid transport domain, thus expanding this family of lipid transporters. Analysis of another candidate, Ypr097w, which we now call Lec1 (Lipid-droplet Ergosterol Cortex 1), revealed that this previously uncharacterized protein dynamically shifts between lipid droplets and the cell cortex, and plays a role in regulation of ergosterol distribution in the cell.

cell biology↗

bioRxiv2021

The genome of New Zealand trevally (Carangidae: Pseudocaranx georgianus) uncovers a XY sex determination locus

BackgroundThe genetic control of sex determinism in teleost species is poorly understood. This is partly because of the diversity of sex determining mechanisms in this large group, including constitutive genes linked to sex chromosomes, polygenic constitutive mechanisms, environmental factors, hermaphroditism, and unisexuality. Here we use a de novo genome assembly of New Zealand silver trevally (Pseudocaranx georgianus) together with whole genome sequencing to detect sexually divergent regions, identify candidate genes and develop molecular makers. ResultsThe de novo assembly of an unsexed trevally (Trevally_v1) resulted in an assembly of 579.4 Mb in length, with a N50 of 25.2 Mb. Of the assembled scaffolds, 24 were of chromosome scale, ranging from 11 to 31 Mb. A total of 28416 genes were annotated after 12.8% of the assembly was masked with repetitive elements. Whole genome re-sequencing of 13 sexed trevally (7 males, 6 females) identified sexually divergent regions located on two scaffolds, including a 6 kb region at the proximal end of chromosome 21. Blast analyses revealed similarity between one region and the aromatase genes cyp19 (a1a/b). Males contained higher numbers of heterozygous variants in both regions, while females showed regions of very low read-depth, indicative of deletions. Molecular markers tested on 96 histologically-sexed fish (42 males, 54 females). Three markers amplified in absolute correspondence with sex. ConclusionsThe higher number of heterozygous variants in males combined with deletions in females support a XY sex-determination model, indicating the trevally_v1 genome assembly was based on a male. This sex system contrasts with the ZW-type sex system documented in closely related species. Our results indicate a likely sex-determining function of the cyp19b-like gene, suggesting the molecular pathway of sex determination is somewhat conserved in this family. Our genomic resources will facilitate future comparative genomics works in teleost species, and enable improved insights into the varied sex determination pathways in this group of vertebrates. The sex marker will be a valuable resource for aquaculture breeding programmes, and for determining sex ratios and sex-specific impacts in wild fisheries stocks of this species.

genomics↗

bioRxiv2021

The status of current and tentative marine natural World Heritage areas

The 1972 World Heritage Convention (WHC), along with the 1994 Global Strategy, aim to preserve the outstanding universal value of internationally important cultural and natural sites within a "representative, balanced and credible" network of highly-protected areas. Increasing human pressures and shortfalls in representation have been documented across the World Heritage network, particularly in terrestrial and cultural sites, threatening the integrity and primary goals of the WHC. However, the conservation status of current and tentative (i.e., proposed) marine natural World Heritage areas remains relatively unknown. We assessed the extent of recent (2013) and historical (2008-2013) cumulative human impacts and several metrics of representation (country, continent, ecoregion, wilderness, and threatened species) within existing and tentative marine natural World Heritage areas. We found moderate yet increasing cumulative human impacts across most existing sites, and high or very high impacts across the majority of tentative sites. Climate change impacts comprised nearly 75% of impact scores, on average, and differences in land and marine impacts across sites could help prioritise management decisions. Over 75% of marine ecoregions and 85% of threatened species considered in this study have no representation within the existing marine natural World Heritage network. We outline examples of how prioritizing representation across tentative sites for future World Heritage listing could greatly increase these measures. We urge the WHC to adopt quantitative, systematic and transparent evaluations of how current and tentative sites contribute to the overarching goals of maintaining a representative World Heritage network and preserving their outstanding universal values for future generations.

ecology↗

bioRxiv2019

A VPS13D spastic ataxia mutation disrupts the conserved adaptor binding site in yeast Vps13

Mutations in each of the four human VPS13 (VPS13A-D) proteins are associated with distinct neurological disorders: chorea-acanthocytosis, Cohen syndrome, early-onset Parkinsons disease and spastic ataxia. Recent evidence suggests that the different VPS13 paralogs transport lipids between organelles at different membrane contact sites. How each VPS13 isoform is targeted to organelles is not known. We have shown that the localization of yeast Vps13 protein to membranes requires a conserved six-repeat region, the Vps13 Adaptor Binding (VAB) domain, which binds to organelle-specific adaptors. Here, we use a systematic mutagenesis strategy to determine the role of each repeat in recognizing each known adaptor. Our results show that mutation of invariant asparagines in repeats 1 and 6 strongly impact the binding all adaptors and block Vps13 membrane recruitment. However, we find that repeats 5 to 6 are sufficient for localization and interaction with adaptors. This supports a model where a single adaptor binding site is found in the last two repeats of the VAB domain, while VAB domain repeat 1 may help maintain domain conformation. Importantly, a disease-causing mutation in VPS13D, which maps to the highly conserved asparagine residue in repeat 6, blocks adaptor binding and Vps13 membrane recruitment when modeled in yeast. Our findings are consistent with a conserved adaptor binding role for the VAB domain and suggests the presence of as-yet-unidentified adaptors in both yeast and humans.

molecular biology↗

bioRxiv2019

Transcranial Alternating Current Stimulation (tACS) Entrains Alpha Oscillations by Preferential Phase Synchronization of Fast-Spiking Cortical Neurons to Stimulation Waveform

Modeling studies predict that transcranial alternating current stimulation (tACS) entrains brain oscillations, yet direct examination has been lacking or potentially contaminated by stimulation artefact. Here we first demonstrate how the posterior parietal cortex drives primary visual cortex and thalamic LP in the alpha-band in head-fixed awake ferrets. The spike-field synchrony is maximum within alpha frequency, and more prominent for narrow-spiking neurons than broad-spiking ones. Guided by a validated model of electric field distribution, we produced electric fields comparable to those in humans and primates (< 0.5 mV/mm). We found evidence to support the model-driven predictions of how tACS entrains neural oscillations as explained by the triangular Arnold tongue pattern. In agreement with the stronger spike-field coupling of narrow-spiking cells, tACS more strongly entrained this cell population. Our findings provide the first in vivo evidence of how tACS with electric field amplitudes used in human studies entrains neuronal oscillators.

neuroscience↗