A5013182680- Microbial infections and disease research
- Veterinary Oncology Research
- Immunotherapy and Immune Responses
- Infectious Diseases and Mycology
- T-cell and B-cell Immunology
- Virus-based gene therapy research
- Ear and Head Tumors
- Rabies epidemiology and control
- Herpesvirus Infections and Treatments
- Immune Cell Function and Interaction
- Reproductive tract infections research
- Genomics and Phylogenetic Studies
- Zoonotic diseases and public health
- Oral and Maxillofacial Pathology
- interferon and immune responses
- Reproductive Physiology in Livestock
- Vaccine Coverage and Hesitancy
- Turtle Biology and Conservation
- vaccines and immunoinformatics approaches
- Genetic and phenotypic traits in livestock
- Immune Response and Inflammation
- Diphtheria, Corynebacterium, and Tetanus
- Chromosomal and Genetic Variations
- Toxoplasma gondii Research Studies
- Animal Disease Management and Epidemiology
The University of Queensland
2023-2025
ARC Centre of Excellence for Plant Success in Nature and Agriculture
2024
University of Southampton
2014-2024
Agriculture and Food
2023-2024
University of Cambridge
2012-2013
The University of Sydney
2006-2012
Australian Research Council
2011
Loss of MHC class I (MHC-I) antigen presentation in cancer cells can elicit immunotherapy resistance. A genome-wide CRISPR/Cas9 screen identified an evolutionarily conserved function polycomb repressive complex 2 (PRC2) that mediates coordinated transcriptional silencing the MHC-I processing pathway (MHC-I APP), promoting evasion T cell-mediated immunity. APP gene promoters low cancers harbor bivalent activating H3K4me3 and H3K27me3 histone modifications, basal expression restricting...
Significance Transmissible cancers are somatic cell lineages that spread between individuals via the transfer of living cancer cells. Only three transmissible have been reported in nature, suggesting such diseases emerge rarely. One known affects Tasmanian devils, and is threatening this species with extinction. Here we report discovery a second devils. This causes facial tumors grossly indistinguishable from those caused by first-described species; however, derived clone genetically...
Contagious cancers that pass between individuals as an infectious cell line are highly unusual pathogens. Devil facial tumor disease (DFTD) is one such contagious cancer emerged 16 y ago and driving the Tasmanian devil to extinction. As both a pathogen allograft, DFTD cells should be rejected by host–immune response, yet causes 100% mortality among infected devils with no apparent rejection of cells. Why not has been question considerable confusion. Here, we show do express surface MHC...
A fatal transmissible tumor spread between individuals by biting has emerged in the Tasmanian devil (Sarcophilus harrisii), a carnivorous marsupial. Here we provide genetic evidence establishing that is clonal and therefore foreign to host devils. Thus, disease highly unusual because it not just but also tissue graft, passed without invoking an immune response. The MHC plays key role responses both tumors grafts. most common mechanism of evasion down-regulation classical cell surface...
Abstract Background We present the genome sequence of tammar wallaby, Macropus eugenii , which is a member kangaroo family and first representative iconic hopping mammals that symbolize Australia to be sequenced. The has many unusual biological characteristics, including longest period embryonic diapause any mammal, extremely synchronized seasonal breeding prolonged sophisticated lactation within well-defined pouch. Like other marsupials, it gives birth highly altricial young, small number...
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...
Tasmanian devils face extinction owing to the emergence of a contagious cancer. Devil facial tumour disease (DFTD) is clonal cancer spread lack major histocompatibility complex (MHC) barriers in devil populations. We present comprehensive screen MHC diversity and identify 25 types 53 novel sequences, but conclude that overall levels at sequence level are low. The majority Class I variation can be explained by allelic copy number with two seven variants identified per individual. sequences...
Devil facial tumour disease (DFTD) is a recently emerged fatal transmissible cancer decimating the wild population of Tasmanian devils (Sarcophilus harrisii). Biting transmits cells and develops in new host as an allograft. The literature reports that immune escape mechanisms employed by DFTD inevitably result death. Here we present first evidence regression can occur mount response against disease. Of 52 tested, six had serum antibodies and, one case, prominent T lymphocyte infiltration its...
Transmissible cancers are clonal lineages that spread through populations via contagious cancer cells. Although rare in nature, two facial tumor clones affect Tasmanian devils. Here we perform comparative genetic and functional characterization of these lineages. The have similar patterns mutation show no evidence exposure to exogenous mutagens or viruses. Genes encoding PDGF receptors copy number gains present on extrachromosomal double minutes. Drug screening indicates causative roles for...
Abstract Devil facial tumour disease (DFTD) is a transmissible cancer devastating the Tasmanian devil ( Sarcophilus harrisii ) population. The cell ‘infectious’ agent transmitted as an allograft by biting. Animals usually die within few months with no evidence of antibody or immune responses against DFTD allograft. This lack anti-tumour immunity attributed to absence surface major histocompatibility complex (MHC)-I molecule expression. While endangerment population precludes experimentation...
The Tasmanian devil (Sarcophilus harrisii) is currently under threat of extinction due to an unusual fatal contagious cancer called Devil Facial Tumour Disease (DFTD). DFTD caused by a clonal tumour cell line that transmitted between unrelated individuals as allograft without triggering immune rejection low levels Major Histocompatibility Complex (MHC) diversity in devils.Here we report the characterization genomic regions encompassing MHC Class I and II genes devil. Four approximately 960...
Devil Facial Tumour 2 (DFT2) is a recently discovered contagious cancer circulating in the Tasmanian devil (Sarcophilus harrisii), species which already harbours more widespread cancer, 1 (DFT1). Here we show that contrast to DFT1, DFT2 cells express major histocompatibility complex (MHC) class I molecules, demonstrating loss of MHC not necessary for emergence cancer. However, most highly expressed alleles are common among host devils or non-polymorphic, reducing immunogenicity population...
Modern conservation science frequently relies on genetic tools to manage imperiled populations threatened by processes such as habitat fragmentation and infectious diseases. Translocation of individuals restore diversity (genetic rescue) is increasingly used vulnerable (Whiteley et al. 2015), but it can swamp local adaptations lead outbreeding depression (Frankham 2011). Thus, management context dependent needs evaluation across multiple generations (Fitzpatrick 2020). Genomic studies help...
Abstract Emerging infectious diseases are rising globally and understanding host‐pathogen interactions during the initial stages of disease emergence is essential for assessing potential evolutionary dynamics designing novel management strategies. Tasmanian devils ( Sarcophilus harrisii ) endangered due to a transmissible cancer—devil facial tumour (DFTD)—that since its in 1990s, has affected most populations throughout Tasmania. Recent studies suggest that adapting DFTD epidemic...
Ecological and evolutionary concepts have been widely adopted to understand host-pathogen dynamics, more recently, integrated into wildlife disease management. Cancer is a ubiquitous that affects most metazoan species; however, the role of oncogenic phenomena in eco-evolutionary processes its implications for management conservation remains undeveloped. Despite pervasive nature cancer across taxa, our ability detect occurrence, progression prevalence populations constrained due logistic...
Summary Naturally transmissible tumours can emerge when a tumour cell gains the ability to pass as an infectious allograft between individuals. The of these colonize new host and cross histocompatibility barriers contradicts our understanding vertebrate immune response allografts. Two naturally occurring contagious cancers are currently active in animal kingdom, canine venereal ( CTVT ), which spreads among dogs, devil facial disease DFTD Tasmanian devils. generally not fatal tumour‐specific...
Abstract Background MHC class I antigens are encoded by a rapidly evolving gene family comprising classical and non-classical genes that found in all vertebrates involved diverse immune functions. However, there is fundamental difference between the organization of mammals non-mammals. Non-mammals have single responsible for antigen presentation, which linked to processing genes, including TAP. This allows co-evolution advantageous Ia/TAP haplotypes. In contrast, multiple within MHC,...
Abstract Background The major histocompatibility complex (MHC) is a group of genes with variety roles in the innate and adaptive immune responses. MHC form genetically linked cluster eutherian mammals, an organization that thought to confer functional evolutionary advantages system. tammar wallaby (Macropus eugenii ), Australian marsupial, provides unique model for understanding gene evolution, as many its antigen presenting are not MHC, but scattered around genome. Results Here we describe...
Devil Facial Tumour Diseases (DFTD), threatening Tasmanian devils, consist of two distinct transmissible cancers, DFT1 and DFT2, with differing origins geographic spread. We investigated the metabolic differences between examining cell viability, outputs, bulk gene expression. Using both DFT2 lines biopsies, we found that glycolysis, oxidative phosphorylation, glutamate metabolism fatty acid synthesis are all essential for survival tumour types. However, exhibited higher rates glycolysis...
The adaptive immune system should prevent cancer cells passing from one individual to another, in much the same way that it protects against pathogens. However, rare cases do not die within a single individual, but successfully pass between individuals, escaping response and becoming contagious cancer. There are two naturally occurring cancers, Devil Facial Tumour Disease (DFTD), found Tasmanian devils, Canine Transmissible Venereal (CTVT), dogs. Despite sharing an ability as allografts,...