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Biology subjects

Ong, C. E. B.

Publications and source records attributed to Ong, C. E. B..

4 recordsLinked to original sources

A Smart Bait Dispenser with Real-time Monitoring for Species-Specific Bait Delivery

1. Remote image capture using trail cameras has become an essential part of many wildlife monitoring and management programs. Oral bait vaccination has been a valuable tool in wildlife disease management, but baits are generally dropped on the ground or delivered by devices that are typically developed to utilise physical and behavioural characteristics of the target species. Both approaches can result in a high proportion of baits being consumed by non-target species. Merging years of trail camera research knowledge with new technologies allows for development of more specific bait delivery options. 2. We developed an open-source smart bait dispenser that uses field-based image classification to selectively deliver baits to the target species. The system's long-range wide area network-based remote telemetry provides updates to an online dashboard in near real time to show camera triggers, target species detections, and baits dispensed. We trialled four dispensers with placebo baits for 62 nights across three field sites in Tasmania, Australia to deliver baits to Tasmanian devil (Sarcophilus harrisii). 3. The dispensers recorded 2106 motion triggers, of which 876 were triggered by animals. The onboard devil classification model achieved 98.6% accuracy, 75.0% precision, 77.4% recall, and a 76.2% F1-score. The dispenser released 41 placebo baits in total, of which 31 were target-specific distributions in response to presence of Tasmanian devils at the dispenser, hence achieving an overall bait delivery success rate of 75.6%. Importantly, no animal was able to forcibly retrieve baits from the dispenser. Observed average battery life across trials was 19.2 nights. 4. These results clearly demonstrate the effectiveness of our innovative bait dispenser for targeted bait delivery, offering a versatile ecological tool that can be tailored for various species by simply updating the image classification model. This adaptable system can support critical initiatives like wildlife oral bait vaccination and supplementary feeding after wildlife translocations.

ecology↗

Regulation of MHC-I and MHC-II by CIITA in transmissible cancers

MHC-I and MHC-II molecules are critical components of antigen presentation and T cell immunity to pathogens and cancer. The two monoclonal transmissible devil facial tumours (DFT1, DFT2) exploit MHC-I pathways to overcome immunological anti-tumour and allogeneic barriers. This exploitation underpins the ongoing transmission of DFT cells across the wild Tasmanian devil population. We have previously shown that constitutive expression of NLRC5 can induce stable upregulation of MHC-I on DFT1 and DFT2 cells, but unlike IFNG-treated cells, NLRC5 does not upregulate PDL1. MHC-II expression is crucial for CD4+ T cell activation and is primarily confined to haematopoietic antigen presenting cells. Transcriptomic analysis of DFT1 and DFT2 cell lines showed that several genes of the MHC-I and MHC-II pathways were upregulated in response to constitutive overexpression of the class II transactivator (CIITA) gene. This was further supported by upregulation of MHC-I protein on DFT1 and DFT2 cells, but interestingly MHC-II protein was upregulated only on DFT1 cells. The functional significance of the MHC upregulation on DFT cells was shown using serum from devils with natural or immunotherapy-induced DFT1 regressions; binding of serum IgG was stronger in CIITA-transfected cells than wild type cells, but was less than binding to NLRC5 transfected cells. This new insight into regulation of MHC-I and MHC-II in cells that naturally overcome allogeneic barriers can inform vaccine, immunotherapy, and tissue transplant strategies for human and veterinary medicine.

immunology↗

NLRC5 regulates expression of MHC-I and provides a target for anti-tumor immunity in transmissible cancers

Downregulation of major histocompatibility complex I (MHC-I) on tumor cells is a primary means of immune evasion by many types of cancer. Additionally, MHC-I proteins are a primary target of immune-mediated transplant rejection. Transmissible tumors that overcome allograft rejection mechanisms and evade anti-tumor immunity have killed thousands of wild Tasmanian devils (Sarcophilus harrisii). Interferon gamma (IFNG) upregulates surface MHC-I expression on devil facial tumor (DFT) cells but is not sufficient to induce tumor regressions. Transcriptome analysis of IFNG-treated DFT cells revealed strong upregulation of NLRC5, a master regulator of MHC-I in humans and mice. To explore the role of NLRC5 in transmissible cancers, we developed DFT cell lines that constitutively overexpress NLRC5. Transcriptomic results suggest that the role of NLRC5 as a master regulator of MHC-I is conserved in devils. Furthermore, NLRC5 was shown to drive the expression of many components of the antigen presentation pathway. To determine if MHC-I is a target of allogeneic immune responses, we tested serum from devils with anti-DFT responses including natural DFT regressions against DFT cells. Antibody binding occurred with cells treated with IFNG and overexpressed NLRC5. However, CRISPR/Cas9-mediated knockout of MHC-I subunit beta-2-microglobulin (B2M) eliminated antibody binding to DFT cells. Consequently, MHC-I could be identified as a target for anti-tumor and allogeneic immunity and provides mechanistic insight into MHC-I expression and antigen presentation in marsupials. NLRC5 could be a promising target for immunotherapy and vaccines to protect devils from transmissible cancers and inform development of transplant and cancer therapies for humans.

immunology↗

Immune checkpoint proteins are conserved across 160 million years of evolution and are expressed on transmissible cancers

Immune checkpoint immunotherapy has revolutionized medicine, but translational success for new treatments remains low. Around 40% of humans and Tasmanian devils (Sarcophilus harrisii) develop cancer in their lifetime, compared to less than 10% for most species. Additionally, devils are affected by two of the three known transmissible cancers in mammals. Unfortunately, little is known about of immune checkpoints in devils and other non-model species, largely due to a lack of species-specific reagents. We developed a simple cut-and-paste reagent development method applicable to any vertebrate species and show that immune checkpoint interactions are conserved across 160 million years of evolution. The inhibitory checkpoint molecule CD200 is highly expressed on devil facial tumor cells. We are the first to demonstrate that co-expression of CD200R1 can block CD200 expression. The evolutionarily conserved pathways suggest that naturally occurring cancers in devils and other species can serve as models for understanding cancer and immunological tolerance. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/831404v3_ufig1.gif" ALT="Figure 1"> View larger version (108K): org.highwire.dtl.DTLVardef@14ff10eorg.highwire.dtl.DTLVardef@15acfd4org.highwire.dtl.DTLVardef@102a37dorg.highwire.dtl.DTLVardef@3b726c_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗