A5037664752- Malaria Research and Control
- Mosquito-borne diseases and control
- Single-cell and spatial transcriptomics
- Genomics and Chromatin Dynamics
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Glycosylation and Glycoproteins Research
- RNA Interference and Gene Delivery
- Platelet Disorders and Treatments
- Zebrafish Biomedical Research Applications
- Genomics and Phylogenetic Studies
- Immune Cell Function and Interaction
- Gene expression and cancer classification
- Vector-borne infectious diseases
- Pluripotent Stem Cells Research
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- Lipid metabolism and disorders
- Digital Imaging for Blood Diseases
- Cell Image Analysis Techniques
- Cancer Genomics and Diagnostics
- Genomic variations and chromosomal abnormalities
- Genetic Associations and Epidemiology
- Cytokine Signaling Pathways and Interactions
- Spectroscopy Techniques in Biomedical and Chemical Research
Walter and Eliza Hall Institute of Medical Research
2013-2024
The University of Melbourne
2004-2024
Google (United Kingdom)
2023
DeepMind (United Kingdom)
2023
Université de Montréal
2013-2015
Institute for Research in Immunology and Cancer
2013
The vast majority of missense variants observed in the human genome are unknown clinical significance. We present AlphaMissense, an adaptation AlphaFold fine-tuned on and primate variant population frequency databases to predict pathogenicity. By combining structural context evolutionary conservation, our model achieves state-of-the-art results across a wide range genetic experimental benchmarks, all without explicitly training such data. average pathogenicity score genes is also predictive...
The human malaria parasite Plasmodium vivax is responsible for 25–40% of the ∼515 million annual cases worldwide. Although seldom fatal, elicits severe and incapacitating clinical symptoms often causes relapses months after a primary infection has cleared. Despite its importance as major pathogen, P. little studied because it cannot be propagated continuously in laboratory except non-human primates. We sequenced genome to shed light on distinctive biological features, means drive development...
Abstract Background The apicomplexan parasite Plasmodium falciparum causes the most severe form of malaria in humans. After invasion into erythrocytes, asexual stages drastically alter their host cell and export remodeling virulence proteins. Previously, we have reported identification functional analysis a short motif necessary for proteins out red blood cell. Results We developed software prediction exported genus , identified conserved between parasites infecting rodents two major human...
Four distinct Plasmodium species are known to regularly infect humans: falciparum, P. vivax, malariae and ovale. The genome sequence of the cause most severe type human malaria, was completed in 2002 at same time as mosquito vector, Anopheles gambiae. In this week's Nature, which focuses on malaria parasite, two further sequences described. First that contributes significant numbers incidence humans, though contrast resulting disease is usually not fatal. rather neglected presented together...
The first sequenced marsupial genome promises to reveal unparalleled insights into mammalian evolution. We have used the Monodelphis domestica (gray short-tailed opossum) sequence construct map of a major histocompatibility complex (MHC). MHC is most gene-dense region and critical immunity reproductive success. bridges phylogenetic gap between eutherian mammals minimal essential birds. Here we show that opossum gene dense complex, as in humans, but shares more organizational features with...
Plasmodium falciparum exports several hundred effector proteins that remodel the host erythrocyte and enable parasites to acquire nutrients, sequester in circulation evade immune responses. The majority of exported contain export element (PEXEL; RxLxE/Q/D) their N-terminus, which is proteolytically cleaved parasite endoplasmic reticulum by Plasmepsin V, necessary for export. Several lack a PEXEL or noncanonical motifs. Here, we assessed whether V could process N-termini diverse protein...
Hematopoiesis is a multistage process involving the differentiation of stem and progenitor cells into distinct mature cell lineages. Here we present Haemopedia, an atlas murine gene-expression data containing 54 hematopoietic types, covering all lineages in hematopoiesis. We include rare populations such as eosinophils, mast cells, basophils, megakaryocytes, broad collection cells. show that lineage branching maturation during hematopoiesis can be reconstructed using expression patterns...
Abstract During embryogenesis, haematopoietic and endothelial lineages emerge closely in time space. It is thought that the first blood endothelium derive from a common clonal ancestor, haemangioblast. However, investigation of candidate haemangioblasts vitro revealed capacity for mesenchymal differentiation, feature more compatible with an earlier mesodermal precursor. To date, no evidence vivo haemangioblast has been discovered. Using single cell RNA-Sequencing cellular barcoding, we have...
ABSTRACT Serine repeat antigens (SERAs) are a family of secreted “cysteine-like” proteases Plasmodium parasites. Several SERAs possess an atypical active-site serine residue in place the canonical cysteine. The human malaria parasite falciparum possesses six “serine-type” ( SERA1 to SERA5 and SERA9 ) three “cysteine-type” SERA6 SERA8 SERAs. Here, we investigate importance serine-type blood-stage development examine extent functional redundancy among this group. We attempted knock out four P....
Analysing multiple cancer samples from an individual patient can provide insight into the way disease evolves. Monitoring expansion and contraction of distinct clones helps to reveal mutations that initiate those drive progression. Existing approaches for clonal tracking sequencing data typically require user combine tools are not purpose-built this task. Furthermore, most methods a matched normal (non-tumour) sample, which limits scope application. We developed SuperFreq, exome analysis...
Accurate quantification of gene expression by qRT-PCR relies on normalization against a consistently expressed control gene. However, genes in common use often vary greatly between samples, especially cancer. The advent Next Generation Sequencing technology offers the possibility to better select with least cell variability steady state transcript levels. Here we analyze transcriptomes 55 leukemia samples identify most consistent genes. This list is enriched for components proteasome (ex....
In a functional genomics screen of mouse embryonic stem cells (ESCs) with nested hemizygous chromosomal deletions, we reveal that ribosomal protein (RP) genes are the most significant haploinsufficient determinants for embryoid body (EB) formation. Hemizygocity three RP (Rps5, Rps14, or Rps28), distinguished by proximity their corresponding to ribosome's mRNA exit site, is associated profound phenotype. This EB phenotype was fully rescued BAC cDNA complementation but not reduction p53...
Estrogen receptors (ERs) regulate gene transcription by interacting with regulatory elements. Most information regarding how ER activates genes has come from studies using a small set of target or simple consensus sequences such as estrogen response element, activator protein 1, and Sp1 However, these elements cannot explain the differences in regulation patterns clinical effects observed estradiol (E(2)) selective receptor modulators. To obtain greater understanding E(2) modulators...
Several species of mycobacteria express abundant glycopeptidolipids (GPLs) on the surfaces their cells. The GPLs are glycolipids that contain modified sugars including acetylated 6-deoxy-talose and methylated rhamnose. Four methyltransferases have been implicated in synthesis Mycobacterium smegmatis avium. A rhamnosyl 3-O-methytransferase a fatty acid methyltransferase M. previously characterized. In this paper, we characterize responsible for modifying hydroxyl groups at positions 2 4...
Abstract In classic ‘ball-and-stick’ models of haematopoiesis the implicit assumption is that all cells within each defined stem or progenitor cell population are equivalent in their fate. Instead, more recent suggest a haematopoietic and (HSPC) ‘continuum’ lineage bias commitment, which largely inferred through ‘snapshot’ analysis single gene expression clonal However, dynamic assessment commitment specific HSPC populations output over time vivo still lacking but essential to fully inform...
Genome-wide transcriptome profiling has enabled non-supervised classification of tumours, revealing different sub-groups characterized by specific gene expression features. However, the biological significance these subtypes remains for most part unclear. We describe herein an interactive platform, Minimum Spanning Trees Inferred Clustering (MiSTIC), that integrates direct visualization and comparison correlation structure between datasets, analysis molecular causes underlying co-variations...
Abstract Conventional single cell RNA-seq methods are destructive, such that a given cannot also then be tested for fate and function, without time machine. Here, we develop clonal method SIS-seq , whereby cells allowed to divide, progeny assayed separately in SIS ter conditions; some fate, others by RNA- seq . By cross-correlating progenitor gene expression with mature within clone, doing this many clones, can identify the earliest signatures of dendritic subset development. could used...