Search bioRxiv⌕ Search

Biology subjects

Jones, A. W.

Publications and source records attributed to Jones, A. W..

4 recordsLinked to original sources

A Novel dual Influenza virus and SARS-CoV-2 neutralisation assay

Influenza and SARS-CoV-2 are co-circulating during the traditional influenza season giving rise to potential co-infections; currently estimated at 2.4%. Additionally, this means that the uptake of both vaccines (including SARS-CoV-2 boosters) will be encouraged within the same timeframe. Currently, patients receive separate vaccines in different arms on the same or different days. Induction of neutralising antibodies (NAbs) is used as the measure of efficacy for SARS-CoV-2 vaccinations while, the hemagglutination inhibition (HI) assay is the gold standard for seasonal influenza vaccine assessment. However, with the advent of novel universal influenza vaccine and dual SARS-CoV-2/Influenza vaccine approaches it is possible that functional NAb assays will become an essential component of a vaccine assessment toolbox. This assay is capable of distinguishing NAb responses during both dual vaccination development, and as part of co-infection and imprinting studies. Taking advantage of existing pseudotyped viruses developed by us, we present herein a dual neutralisation assay, which utilises 2 different luciferase (Renilla and Firefly) reporter lentiviral vectors. We configured assays with various combinations of SARS-CoV-2 and influenza subtype/variant combinations and compared sensitivity of this dual approach to neutralisation levels seen in single virus pseudotype Micro-neutralisation (pMN) in a double-blinded test of monoclonal antibody cocktails, and subsequently with a pre-screened serum panel. Mono and dual neutralisation pMN identified correctly positive and negative samples and IC50 values were all within 2-fold of each other, suggesting that specificity and sensitivity are retained post-multiplex. As we have taken a pseudovirus based approach there is the potential to tailor to specific vaccination candidates or currently circulating strains of each virus. The use of this versatile assay could form part of the toolbox of analysis of dual vaccination candidates and investigating responses during co-infection including studies assessing the impact of immune imprinting in the future.

immunology↗

Population genetic consequences of the seasonal migrations of birds

Differences in life history can cause co-distributed species to display discordant population genetic patterns. In high-latitude animals, evolutionary processes may be especially influenced by long-distance seasonal migration, a widespread adaptation to seasonality. Although migratory movements are intuitively linked to dispersal, their evolutionary genetic consequences remain poorly understood. Using [~]1700 genomes from 35 co-distributed boreal-breeding bird species, we reveal that most long-distance migrants exhibit spatial genetic structure, revealing evolutionary effects of philopatry rather than dispersal. We further demonstrate that migration distance and genetic diversity are strongly positively correlated in our study species. This striking relationship suggests that the adaptive seasonal shifts in biogeography that long-distance migratory species undergo each year lends them enhanced population stability that preserves genetic diversity relative to shorter-distance migrants that winter at higher latitudes. Our results suggest that the major impact of long-distance seasonal migration on population genetic evolution occurs through promotion of demographic stability, rather than facilitation of dispersal.

evolutionary biology↗

How Veeries vary: Whole genome sequencing resolves fine-scale genetic structure in a long-distance migratory bird, Catharus fuscescens

Fine-scale resolution of spatial genetic structure is important for understanding a species evolutionary history and contemporary genetic diversity. For high-latitude species with high dispersal ability, such as long-distance migratory birds, populations typically exhibit little genetic structure due to high gene flow and recent postglacial expansion. Some migratory birds, however, show high breeding site fidelity, which might reduce gene flow such that population genetic structure could be detectable with sufficient genomic data. We sequenced over 120 low-coverage whole genomes from across the breeding range of a long-distance migratory bird, the Veery (Catharus fuscescens). As this species breeding range extends across both historically glaciated and unglaciated regions in North America, we evaluated whether contemporary patterns of structure and genetic diversity are consistent with historical population isolation in glacial refugia. We found strong evidence for isolation by distance across the breeding range, as well as significant population structure between southern Appalachian and northern populations. However, patterns of genetic diversity did not support southern Appalachia as a glacial refugium. Resolution of isolation by distance across the breeding range was sufficient to assign likely breeding origins of individuals sampled in this species poorly understood South American nonbreeding range, demonstrating the potential to assess migratory connectivity in this species using genomic data. Overall, our findings suggest that isolation by distance yields subtle associations between genetic structure and geography across the breeding range even in the absence of obvious historical vicariance or contemporary barriers to dispersal.

evolutionary biology↗

RNA polymerase II dynamics and mRNA stability feedback determine mRNA scaling with cell size

A fundamental feature of cellular growth is that protein and RNA amounts scale with cell size so that concentrations remain constant. A key component to this is that global transcription rates increase in larger cells, but the underlying mechanism has remained unknown. Here, we identify RNAPII as the major limiting factor increasing transcription with cell size in budding yeast as transcription is highly sensitive to the dosage of RNAPII but not to other components of the general transcriptional machinery. Our experiments support a dynamic equilibrium model where global transcription at a given size is set by the mass-action recruitment kinetics of unengaged nucleoplasmic RNAPII, and DNA content. This drives a sub-linear increase in transcription with size, which is precisely compensated for by a decrease in mRNA decay rates as cells enlarge. Thus, limiting RNAPII and feedback on mRNA stability work in concert to ensure mRNA concentration homeostasis in growing cells.

molecular biology↗