Immune regulation of preterm birth
This honours project in molecular and biomedical science will investigate immune regulation of preterm birth.
Macrophages are present in large numbers in the gestational tissues throughout the course of pregnancy and are prominent around the time of birth, as well as in preterm birth (<34 weeks gestation). Macrophages are implicated in critical roles in the timing of delivery, their precocious activation may be a central event in infection-induced preterm delivery.
Our recent studies suggest that so-called ‘M2’ macrophages exert potent anti-inflammatory and immune suppressive functions in the gestational tissues, where they prevent inflammation to maintain quiescense of the maternal immune response and sustain pregnancy until term.
To investigate the roles of macrophages during late gestation pregnancy, this project will utilise CD11b-DTR transgenic mice to elicit transient systemic ablation of macrophages by administration of low dose diphtheria toxin (DT). The effects of macrophage ablation during late gestation on the incidence of preterm delivery, as well as the underlying mechanistic pathways, will be evaluated.
In particular, the project will focus on the roles of M2 macrophages in sustaining Treg cell populations and preventing NK cell and Th17 cell activation.
The project will use a range of experimental strategies including quantitative RT-PCR for gene expression analysis, fluorescent histochemistry and flow cytometry (FACS).
The findings will help us understand the importance of macrophages in controlling the timing of birth and in particular their relationship to preterm birth. Disruptions in M2 macrophages may be linked with the very high incidence of preterm birth in Western and developing countries (9-12% of all births) which is the most common cause of post-natal morbidity and mortality, as well as having life-long consequences in children born too soon.
Study reproductive immunology
We seek to unravel the immune and cytokine networks of early pregnancy to understand how maternal immune tolerance to pregnancy is established, and how failure in this process contributes to infertility, miscarriage and pregnancy disorders. Our work also has applications in animal breeding industries where early pregnancy loss is a significant constraint.
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