Biology subjects

Lawrence, S.

Publications and source records attributed to Lawrence, S..

9 recordsLinked to original sources

bioRxiv2025

Invasion blurs the biphasic mosaic, amplifies the 'wicked problem' through impacts on avian distributions in montane habitats.

Globally, managing invasive plants and habitat transformation often constitutes a wicked problem due to highly variable impacts on threatened biodiversity. In naturally patchy habitats, invasion can blur edges, pushing species beyond natural habitats. In biphasic habitats like forest-grassland mosaics, complementary sets of specialist species offer a unique configuration to examine such impacts from both directions. In the Shola Sky Islands, extensive woody invasive stands and agriculture/production landscapes have created a set of transformed closed and open habitats structurally similar to their natural counterparts. We expect the species usage of such novel habitats to reflect their dietary and habitat specialisation. We conducted 4,519 surveys across 1,204 randomly selected grid cells for the avian community, covering the global distribution of five species. For a select set of specialist and generalist species, we estimated patch occupancy and abundance using hierarchical models. We used acoustics to assess species persistence across invasion stages with automated recorders deployed across a year. We used community occurrence data to examine functional traits that correspond to habitat colonisation. Forest species occur year-round in transformed woody habitats across all invasion stages, and habitat overstory determines avian functional diversity. Forest specialists decline in transformed habitats across high-contrast edges, while generalists increase across both high- and low-contrast edges, indicating a supertramp strategy. Grassland specialist, however, decline strongly beyond all edges, creating a duality of losses and gains across the biphasic matrix. We highlight the diversity of threatened species responses to invasion and habitat transformation, underscoring the importance of nuanced approaches to habitat restoration, particularly in biphasic habitats.

ecology↗

bioRxiv2025

rTCT: Rodent Triangle Completion Task to facilitate translational study of path integration

Path integration is navigation in the absence of environmental landmarks and is a primary cognitive mechanism underlying spatial memory. Path integration performance is primarily assessed in humans using the Triangle Completion Task (TCT). In humans, TCT has shown promise for the early diagnosis of Alzheimers disease. In rodents, however, path integration is assessed using a wide variety of tasks but none of which currently provide a homologue for the TCT. As rodents are routinely used as preclinical models, homologous path integration tasks that result in comparable performance metrics between species are important. In the present study we developed and tested a novel rodent version of the triangle completion task to enhance cross species comparability of path integration performance. Rats were able to comprehend and perform the task. A group of Alzheimers disease model rats (TgF344-AD) exhibited similar path integration performance to their wild-type littermates; however, analysis of behavioural structure suggests use of differing behavioural strategies. This work establishes a novel rodent homologue of the triangle completion task, facilitating enhanced reverse translational study of human path integration.

neuroscience↗

bioRxiv2024

APOBEC shapes tumor evolution and age at onset of lung cancer in smokers

APOBEC enzymes are part of the innate immunity and are responsible for restricting viruses and retroelements by deaminating cytosine residues1,2. Most solid tumors harbor different levels of somatic mutations attributed to the off-target activities of APOBEC3A (A3A) and/or APOBEC3B (A3B)3-6. However, how APOBEC3A/B enzymes shape the tumor evolution in the presence of exogenous mutagenic processes is largely unknown. Here, by combining deep whole-genome sequencing with multi-omics profiling of 309 lung cancers from smokers with detailed tobacco smoking information, we identify two subtypes defined by low (LAS) and high (HAS) APOBEC mutagenesis. LAS are enriched for A3B-like mutagenesis and KRAS mutations, whereas HAS for A3A-like mutagenesis and TP53 mutations. Unlike APOBEC3A, APOBEC3B expression is strongly associated with an upregulation of the base excision repair pathway. Hypermutation by unrepaired A3A and tobacco smoking mutagenesis combined with TP53-induced genomic instability can trigger senescence7, apoptosis8, and cell regeneration9, as indicated by high expression of pulmonary healing signaling pathway, stemness markers and distal cell-of-origin in HAS. The expected association of tobacco smoking variables (e.g., time to first cigarette) with genomic/epigenomic changes are not observed in HAS, a plausible consequence of frequent cell senescence or apoptosis. HAS have more neoantigens, slower clonal expansion, and older age at onset compared to LAS, particularly in heavy smokers, consistent with high proportions of newly generated, unmutated cells and frequent immuno-editing. These findings show how heterogeneity in mutational burden across co-occurring mutational processes and cell types contributes to tumor development, with important clinical implications.

genomics↗

bioRxiv2023

Spatially resolved single-cell atlas of the lung in fatal Covid19 in an African population reveals a distinct cellular signature and an interferon gamma dominated response

Postmortem single-cell studies have transformed understanding of lower respiratory tract diseases (LRTD) including Covid19 but there is almost no data from African settings where HIV, malaria and other environmental exposures may affect disease pathobiology and treatment targets. We used histology and high-dimensional imaging to characterise fatal lung disease in Malawian adults with (n=9) and without (n=7) Covid19, and generated single-cell transcriptomics data from lung, blood and nasal cells. Data integration with other cohorts showed a conserved Covid19 histopathological signature, driven by contrasting immune and inflammatory mechanisms: in the Malawi cohort, by response to interferon-gamma (IFN-{gamma}) in lung-resident alveolar macrophages, in USA, European and Asian cohorts by type I/III interferon responses, particularly in blood-derived monocytes. HIV status had minimal impact on histology or immunopathology. Our study provides data resources and highlights the importance of studying the cellular mechanisms of disease in underrepresented populations, indicating shared and distinct targets for treatment.

immunology↗

bioRxiv2023

A human prenatal skin cell atlas reveals immune cell regulation of skin morphogenesis

Human prenatal skin is populated by innate immune cells including macrophages, and whether they act solely in immunity or have additional functions in morphogenesis is unclear. We assembled the first comprehensive multi-omic reference atlas of prenatal human skin (7-16 post-conception weeks), combining single cell and spatial transcriptomic data, to characterise the skins microenvironmental cellular organisation. This revealed that crosstalk between non-immune and immune cells underpins formation of hair follicles, has implications for scarless wound healing, and is critical for skin angiogenesis. We benchmarked a skin organoid model, derived from human embryonic stem (ES) and induced pluripotent stem (iPS) cells, against prenatal and adult skin, demonstrating close recapitulation of the epidermal and dermal skin components during hair follicle development. Notably, the skin organoid lacked immune cells and had markedly diminished endothelial cell heterogeneity and quantity. From our in vivo skin cell atlas data, we found that macrophages and macrophage-derived growth factors play a key role in driving endothelial development prenatally. Indeed, vascular network formation was enhanced following transfer of autologous iPS-derived macrophages into both endothelial cell angiogenesis assays and skin organoid cultures. In summary, innate immune cells moonlight as key players in skin morphogenesis beyond their conventional immune roles, a function they achieve via extensive crosstalk with non-immune cells. Finally, we leveraged our human prenatal skin cell atlas to further our understanding of the pathogenesis of genetic hair and skin disorders.

developmental biology↗

bioRxiv2023

Dance or disappear: Strategic sexual signalling in Peninsular rock agama

Sexual signalling has largely been studied in the context of indirect competition among males through displays and mate choice by females. Historically, sexual signalling in females was expected to be of limited consequence. However, there is growing evidence of sexual signalling in females and its value in the context of sexual selection. Here, we test how females strategize the use of sexual signals in a socially polygynous lizard, Psammophilus dorsalis. We evaluated key hypotheses for how females should modulate their signalling, including male quality and mate availability. We simulate male quality using artificial male models to individually tagged, and intensely monitored wild female lizards, measuring their strategic investment in sexual signalling. We found that females invest more in signalling towards high quality males and increased their investment towards the later part of the only breeding season. Contrary to what is typically expected in a polygynous mating system, females not only invest in costly and elaborate sexual signals, they also modulate their usage to maximise their benefits and minimise their costs. Even in polygynous mating systems, dispersed distribution of individuals can result in females experiencing limitation in mate availability, resulting in costly sexual signalling.

ecology↗

bioRxiv2022

Patterns of secondary invasion in the understory of exotic, invasive timber stands

Current climate and land cover change threaten global mountaintops with increased spread of invasive species. Long-established plantations of exotic and invasive trees on these mountaintops can alter their surroundings, further increasing invader-facilitated or secondary invasion. Identifying the ecological conditions that promote such specific associations can help develop better management interventions. The Western Ghatss Shola Sky Islands (>1400m MSL) host vast stretches of exotic and invasive tree plantations that sustain colonisation of other invasive woody, herbaceous and fern species in their understories. Here we analysed vegetation and landscape variables from 232 systematically-placed plots in randomly selected grids using NMDS and Phi Coefficient approaches, to examine patterns of association (positive interactions) between secondary understory invasive species with specific exotic and invasive overstory species. We also conducted GLMM with zero inflation to determine the influence of environmental variables where such associations occur. We find that secondary invasion of multiple species under the canopy of other exotic invasives is widespread across the Shola Sky Islands. Stands of Eucalyptus host the colonisation of 70% of non-native invasive species surveyed across the Shola Sky Islands. In particular, Lantana camara invasion is strongly associated with Eucalyptus stands. We also found that climatic variables affect the colonisation of understorey woody invasive species, while invasion by exotic herbaceous species is associated with the density of road networks.. Canopy cover impacts all invasives negatively, while incidence of fire was negatively associated with invasion by Lantana spp and the Pteridium spp. While the restoration of natural habitats largely targets the highly invasive Acacia, less invasive Eucalyptus and Pine are often not included. Our study suggests that retaining such exotic species in natural habitats, particularly protected areas, can hinder ongoing restoration efforts by facilitating further invasions by multiple woody and herbaceous species.

ecology↗

bioRxiv2021

A tyrosine-based trafficking signal in the simian immunodeficiency virus envelope cytoplasmic domain is strongly selected for in pathogenic SIV infection

The HIV/SIV envelope glycoprotein (Env) cytoplasmic domain contains a highly conserved Tyr-dependent trafficking signal that mediates both clathrin-dependent endocytosis and polarized sorting of Env. Despite extensive characterization, the role of these functions in viral infection and pathogenesis is unclear. An SIV molecular clone (SIVmac239) in which the Tyr-based signal is inactivated by deletion of Gly-720 and Tyr-721 (SIVmac239{Delta}GY) replicates to high levels acutely in pigtail macaques (PTM) but is rapidly controlled. We previously reported that rhesus macaques and PTM can progress to AIDS following SIVmac239{Delta}GY infection in association with novel amino acid changes in the Env cytoplasmic domain. These included an R722G flanking the {Delta}GY deletion and a nine nucleotide deletion that encodes amino acids 734-736 ({Delta}QTH) and overlaps with the rev and tat open reading frames. We show that molecular clones containing these mutations reconstitute signals for both endocytosis and polarized sorting. In one PTM, a novel genotype was selected, which generated a new signal for polarized sorting but not endocytosis. This mutation by itself was sufficient to maintain high viral loads for several months when introduced into naive PTMs. These findings reveal, for the first time, strong selection pressure for Env endocytosis and, in particular, for polarized sorting during pathogenic SIV infection in vivo.

cell biology↗

bioRxiv2021

Single-molecule super-resolution imaging of T-cell plasma membrane CD4 redistribution upon HIV-1 binding

The first step of cellular entry for the human immunodeficiency virus type-1 (HIV-1) occurs through the binding of its envelope protein (Env) with the plasma membrane receptor CD4 and co-receptor CCR5 or CXCR4 on susceptible cells, primarily CD4+ T cells and macrophages. Although there is considerable knowledge of the molecular interactions between Env and host cell receptors that lead to successful fusion, the precise way in which HIV-1 receptors redistribute to sites of virus binding at the nanoscale remains unknown. Here, we quantitatively examine changes in the nanoscale organisation of CD4 on the surface of CD4+ T cells following HIV-1 binding. Using single-molecule super-resolution imaging, we show that CD4 molecules are distributed mostly as either individual molecules or small clusters of up to 4 molecules. Following virus binding, we observe a local 3-to-10-fold increase in cluster diameter and molecule number for virus-associated CD4 clusters. Moreover, a similar but smaller magnitude reorganisation of CD4 was also observed with recombinant gp120. For the first time, our results quantify the nanoscale CD4 reorganisation triggered by HIV-1 on host cells. Our quantitative approach provides a robust methodology for characterising the nanoscale organisation of plasma membrane receptors in general with the potential to link spatial organisation to function.

biophysics↗