ORCID Profile
0000-0001-5411-2807
Current Organisations
University of Cambridge
,
University of Oxford
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Publisher: American Association for the Advancement of Science (AAAS)
Date: 23-08-2019
Abstract: Several species of the parasite Plasmodium cause human malarial diseases, and, despite determined control efforts, a huge global disease burden remains. Howick et al. present a single-cell analysis of transcription across the malaria parasite life cycle (see the Perspective by Winzeler). Single-cell transcriptomes generated from 10 different life-cycle stages of the rodent-model malaria parasite P. berghei identified 20 “modules” among 5156 core transcriptome genes. These clusters enabled functional assignment of hypothetical and conserved genes, and they hint at further substructure of established life-cycle stages. The atlas also allowed for P. falciparum and P. malariae transcriptomes from patient isolates to be deconvoluted and for classification of parasitemia according to developmental stage. Science , this issue p. eaaw2619 see also p. 753
Publisher: Cold Spring Harbor Laboratory
Date: 19-08-2021
DOI: 10.1101/2021.08.18.456784
Abstract: Maturation rate of malaria parasites within red blood cells (RBC) can be influenced by host nutrient status or circadian rhythm. Here, we observed in mice that systemic host inflammation, induced by lipopolysaccharide (LPS) conditioning or ongoing acute malaria infection, slowed the progression of a single cohort of parasites from one generation of RBC to the next. LPS-conditioning and acute infection both triggered substantial changes to the metabolomic composition of plasma in which parasites circulated. This altered plasma directly slowed parasite maturation in a manner that could not be rescued by supplementation, consistent with the presence of inhibitory factors. Single-cell transcriptomic assessment of mixed parasite populations, exposed to a short period of systemic host inflammation in vivo , revealed specific impairment in the transcriptional activity and translational capacity of trophozoites compared to rings or schizonts. Thus, we provide in vivo evidence of transcriptomic and phenotypic plasticity of asexual blood-stage Plasmodium parasites when exposed to systemic host inflammation.
Publisher: Cold Spring Harbor Laboratory
Date: 03-04-2023
DOI: 10.1101/2023.04.01.535228
Abstract: Recent technological innovations have enabled the high-throughput quantification of gene expression and epigenetic regulation within in idual cells, transforming our understanding of how complex tissues are constructed. Missing from these measurements, however, is the ability to routinely and easily spatially localise these profiled cells. We developed a strategy, Slide-tags, in which single nuclei within an intact tissue section are ‘tagged’ with spatial barcode oligonucleotides derived from DNA-barcoded beads with known positions. These tagged nuclei can then be used as input into a wide variety of single-nucleus profiling assays. Application of Slide-tags to the mouse hippoc us positioned nuclei at less than 10 micron spatial resolution, and delivered whole-transcriptome data that was indistinguishable in quality from ordinary snRNA-seq. To demonstrate that Slide-tags can be applied to a wide variety of human tissues, we performed the assay on brain, tonsil, and melanoma. We revealed cell-type-specific spatially varying gene expression across cortical layers and spatially contextualised receptor-ligand interactions driving B-cell maturation in lymphoid tissue. A major benefit of Slide-tags is that it is easily adaptable to virtually any single-cell measurement technology. As proof of principle, we performed multiomic measurements of open chromatin, RNA, and T-cell receptor sequences in the same cells from metastatic melanoma. We identified spatially distinct tumour subpopulations to be differentially infiltrated by an expanded T-cell clone and undergoing cell state transition driven by spatially clustered accessible transcription factor motifs. Slide-tags offers a universal platform for importing the compendium of established single-cell measurements into the spatial genomics repertoire.
Publisher: Cold Spring Harbor Laboratory
Date: 22-01-2019
DOI: 10.1101/527556
Abstract: Malaria parasites adopt a remarkable variety of morphological life stages as they transition through multiple mammalian host and mosquito vector environments. Here we profile the single-cell transcriptomes of thousands of in idual parasites, deriving the first high-resolution transcriptional atlas of the entire Plasmodium berghei life cycle. We then use our atlas to precisely define developmental stages of single cells from three different human malaria parasite species, including parasites isolated directly from infected in iduals. The Malaria Cell Atlas provides both a comprehensive view of gene usage in a complex eukaryotic parasite and an open access reference data set for the study of malaria parasites.
Publisher: Cold Spring Harbor Laboratory
Date: 04-08-2021
DOI: 10.1101/2021.08.04.455056
Abstract: The transmission of malaria parasites from vertebrate host to mosquito vector requires a developmental switch in asexually iding blood-stage parasites to sexual reproduction. In Plasmodium berghei the transcription factor AP2-G is required and sufficient for this switch, but how a particular sex is determined in a haploid parasite remains unknown. Using a global screen of barcoded mutants, we here identify ten genes essential for the formation of either male or female sexual forms and validate their importance for transmission. High-resolution single-cell transcriptomics of wild-type and mutant parasites portrays the developmental bifurcation and reveals a regulatory cascade of putative gene functions in determination and subsequent differentiation of each sex. A male-determining gene with a LOTUS/OST-HTH domain points towards unexpected conservation of molecular mechanisms of gametogenesis in animals and a distantly related eukaryotic parasite.
Publisher: Elsevier BV
Date: 02-2023
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Andrew Russell.