An opportunity exists for a driven and passionate student to undertake a fully-funded 4 year PhD under the supervision of Prof. Amanda Sferruzzi-Perri and Dr. Kathryn Wolton assessing the impacts of xenobiotics on human placenta development and function. As the placenta is perfused with maternal blood, xenobiotics circulating in the mother easily reach the placenta. These can accumulate and compromise placental formation and function with consequences for fetal development, and subsequent adult health. Despite this, the placenta remains largely ignored in traditional toxicology studies. This joint project will exploit the Sferruzzi-Perri lab’s expertise in placental physiology and Dr. Wolton’s experience in developmental and reproductive toxicology. The project will utilise human trophoblast cell models including 3D cultures to systematically assess the impacts of xenobiotics on viability, cytotoxicity, differentiation, nutrient uptake, and hormone secretion. The potential for synergistic or additive toxicity based on co-exposures with xenobiotics will also be studied. Toxicodynamic data will be coupled with toxicokinetic modelling to understand the exposure conditions required to elicit functional effects on human trophoblast cells. Functional changes caused by xenobiotic exposure will be related to alterations in trophoblast metabolism, oxidative stress, apoptotic pathways, and inflammatory cytokine release. The mechanisms underlying trophoblast alterations will be uncovered through high throughput analyses, such as RNA-sequencing and metabolomics, with targeted validation experiments depending on the findings.
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