Biology subjects

Bennett, K. L.

Publications and source records attributed to Bennett, K. L..

7 recordsLinked to original sources

bioRxiv2026

Invasion history of Aedes (Stegomyia) albopictus into Mesoamerica based on mitogenomes and Wolbachia symbionts: Multiple introductions with temperate origins.

The global invasion of the Asian tiger mosquito Aedes albopictus has led to an increase in arboviral disease, including within Mesoamerica. Understanding vector invasion routes is important for public health because it directs biosecurity and identifies sources of adaptive allele spread. Panama is an important hub of global trade with opportunities for Aedes introduction through both maritime and overland routes but dispersal into the Isthmus has not yet been investigated. We therefore sought to investigate the population structure and invasion history of Ae. albopictus into Panama, targeting both its mitogenome and associated Wolbachia. Historical demographic analysis with Bayesian phylogeographic diffusion models and estimates of divergence revealed that Panamanian Ae. albopictus and its associated Wolbachia have a convergent evolutionary history resulting from multiple introductions. Both could be traced to Asian-derived lineages introduced via the Americas, with invasion primarily through the maritime trade of the Panama Canal rather than overland dispersal from neighboring Costa Rica. An investigation of the relative density of Wolbachia in Panama revealed that both the strains wAlbB and wAlbA were at a notably lower density compared to other worldwide locations. This finding has implications for arbovirus transmission and raises important questions about how Wolbachia density is impacted by the environment and impacts on population control. Overall, the Panama Canal is a key route for vector introductions into Mesoamerica.

evolutionary biology↗

bioRxiv2026

Genomic signatures of selection in Anopheles funestus reveal shared and population-specific adaptive variation across African populations

Insecticide resistance in Anopheles funestus threatens malaria vector control across sub-Saharan Africa, yet genomic signatures of selection across geographically structured populations remain poorly understood. We analysed whole-genome sequence data from 635 An. funestus mosquitoes from West (Senegal, Guinea, Nigeria), Central (Cameroon), and East Africa (Kenya) to characterise population structure and identify targets of recent positive selection. Population genomic analyses revealed strong differentiation between East African and West/Central African populations, with finer-scale structuring within West Africa. Genome-wide selection scans using H12 identified sweep regions on chromosome arms 2RL and 3RL, overlapping a cytochrome P450 cluster and the gamma-aminobutyric acid (GABA) receptor locus respectively. iSAFE prioritised candidate variants within these sweeps: non-synonymous substitutions in CYP6A14 were identified at high frequencies in Guinea, Nigeria, and Cameroon, while population-restricted variants implicated octopamine receptor genes on 2RL and the GABA receptor on 3RL. Diplotype clustering and copy number variation analyses confirmed the causal role of candidate variants, embedded within extended haplotypes of reduced heterozygosity consistent with recent positive selection. These findings demonstrate that adaptive evolution in An. funestus reflects both shared and population-specific selective processes shaped by geography and ecological context. Whereas selection on detoxification pathways appears widespread, localised signals in neuromodulatory loci, including the GABA receptor and octopamine-related genes, reveal that biological systems beyond metabolic resistance contribute to mosquito adaptation. The convergence of selective signals across these gene classes highlights neuromodulatory pathways as potential complementary targets for next-generation vector control strategies.

genomics↗

bioRxiv2021

MICS1 is the Ca2+ /H+ antiporter of mammalian mitochondria

Mitochondrial Ca2+ ions are crucial regulators of bioenergetics, cell death pathways and cytosolic Ca2+ homeostasis. Mitochondrial Ca2+ content strictly depends on Ca2+ transporters. In recent decades, the major players responsible for mitochondrial Ca2+ uptake and release have been identified, except the mitochondrial Ca2+/H+ exchanger (CHE). Originally identified as the mitochondrial K+/H+ exchanger, LETM1 was also considered as a candidate for the mitochondrial CHE. Defining the mitochondrial interactome of LETM1, we identified MICS1, the only mitochondrial member of the TMBIM family. Applying cell-based and cell-free biochemical assays, here we demonstrate that MICS1 is responsible for the Na+- and permeability transition pore-independent mitochondrial Ca2+ release and identify MICS1 as the long-sought mitochondrial CHE. This finding provides the final piece of the puzzle of mitochondrial Ca2+ transporters and opens the door to exploring its importance in health and disease, and to developing drugs modulating Ca2+ exchange.

biochemistry↗

bioRxiv2019

Ifnar1 signaling breaks the hepatic urea cycle to regulate adaptive immunity

Infections induce complex host responses linked to antiviral defense, inflammation and tissue damage and repair. These processes are increasingly understood to involve systemic metabolic reprogramming. We hypothesized that the liver as a central metabolic hub may orchestrate many of these changes during infection. Thus, we investigated the systemic interplay between inflammation and metabolism in a mouse model of chronic viral infection and hepatitis. Here we show that virus-induced type I interferon (IFN-I) modulates wide-spread metabolic alterations of the liver in a hepatocyte-intrinsic Ifnar1-dependent way. Specifically, IFN-I repressed the transcription of numerous genes with metabolic function including Otc and Ass1, which encode enzymes of the urea cycle. This led to decreased arginine and increased ornithine concentrations in the circulation, resulting in suppressed virus-specific CD8 T cell responses and ameliorated liver pathology. These findings establish IFN-I-induced modulation of hepatic metabolism and the urea cycle as an endogenous mechanism of immunoregulation.

immunology↗

bioRxiv2019

The impact of local adaptation and biological invasion on the geographical distribution of Aedes aegypti in Panama

Local adaptation is an important consideration when predicting arthropod-borne disease risk because it can impact on vector population fitness and persistence. However, the extent that vector populations are adapted to local environmental conditions and whether this can impact on species distributions generally remains unknown. Here we find that the geographic distribution of Ae. aegypti across Panama is rapidly changing as a consequence of the recent invasion by its ecological competitor, Aedes albopictus. Although Ae. albopictus has displaced Ae. aegypti in some areas, species coexist across many areas, raising the question: What biological and environmental factors permit population persistence?. Despite low population structure and high gene flow in Ae. aegypti across Panama, excepting the province of Bocas del Toro, we identify 128 candidate SNPs, clustered within 17 genes, which show a strong genetic signal of local adaptation. This putatively adaptive variation occurs across relatively fine geographic scales with the composition and frequency of candidate adaptive loci differing between populations in wet tropical environments along the Caribbean coast and the dry tropical conditions typical of the Pacific coast of Panama. Temperature and vegetation were important predictors of adaptive genomic variation in Ae. aegypti with potential areas of local adaptation occurring within the Caribbean region of Bocas del Toro, the Pacific coastal areas of Herrera and Panama City and the eastern Azuero Peninsula. Interestingly, several of these locations coincide with areas where Ae. aegypti and Ae. albopictus co-exist, suggesting that Ae. aegypti could have an adaptive edge under local environmental conditions that impacts on inter-specific competition with Ae. albopictus. Our results guide future experimental work by suggesting that locally adapted Ae. aegypti are able to persist on invasion by Ae. albopictus and, as a consequence, may fundamentally alter future arborviral disease risk and efforts to control mosquito populations. Author SummaryLocal environmental adaptation of mosquito vectors can alter the landscape of arthropod-borne disease by impacting on life history traits that increase their relative fitness thus promoting population persistence. We have identified a number of genomic loci in Ae. aegypti from Panama that exhibit a signal of natural selection associated with variation in the environment. Loci with a signal of local adaptation are predominately partitioned between wet and dry tropical environments with variation largely impacted by temperature and vegetation indices. Local adaptation in tandem with changes in the geographic distribution of Ae. aegypti due to the recent invasion of its ecological competitor, Ae. albopictus, has the potential to alter the landscape of arborviral disease.

evolutionary biology↗

bioRxiv2018

MTHFD1 is a genetic interactor of BRD4 and links folate metabolism to transcriptional regulation

The histone acetyl-reader BRD4 is an important regulator of chromatin structure and transcription, yet factors modulating its activity have remained elusive. Here we describe two complementary screens for genetic and physical interactors of BRD4, which converge on the folate pathway enzyme MTHFD1. We show that a fraction of MTHFD1 resides in the nucleus, where it is recruited to distinct genomic loci by direct interaction with BRD4. Inhibition of either BRD4 or MTHFD1 results in similar changes in nuclear metabolite composition and gene expression, and pharmacologic inhibitors of the two pathways synergize to impair cancer cell viability in vitro and in vivo. Our finding that MTHFD1 and other metabolic enzymes are chromatin-associated suggests a direct role for nuclear metabolism in the control of gene expression.

cancer biology↗

bioRxiv2018

The ERBB-STAT3 Axis Drives Tasmanian Devil Facial Tumor Disease

The marsupial Tasmanian devil (Sarcophilus harrisii) faces extinction due to transmissible devil facial tumor disease (DFTD). To unveil the molecular underpinnings of DFTD, we designed an approach that combines sensitivity to drugs with an integrated systems-biology characterization. Sensitivity to inhibitors of the ERBB family of receptor tyrosine kinases correlated with their overexpression, suggesting a causative link. Proteomic and DNA methylation analyses revealed tumor-specific signatures linked to oncogenic signaling hubs including evolutionary conserved STAT3. Indeed, ERBB inhibition blocked phosphorylation of STAT3 and arrested cancer cells. Pharmacological blockade of ERBB signaling prevented tumor growth in a xenograft model and resulted in recovery of MHC class I gene expression. This link between the hyperactive ERBB-STAT3 axis and MHC class I mediated tumor immunosurveillance provides mechanistic insights into horizontal transmissibility and led us to the proposition of a dual chemo-immunotherapeutic strategy to save Tasmanian devils from DFTD.

cancer biology↗