How is offspring immunity set during development?
Supervisors: Dr Jens Kieckbusch / Dr Francesco Colucci
The placenta nourishes the fetus. When the placenta develops abnormally, fetal growth is often affected. Low birth weight (LBW) underlies much perinatal mortality and morbidity and the ‘fetal origins’ hypothesis proposes that the gestation period impacts also on adult health. Recent studies have focussed on non-communicable diseases (e.g. cardiovascular and metabolic pathology) but infectious diseases are an imminent threat where the incidence of LBW is high. Indeed, neonates are naturally susceptible to infections and when born small their immune system is even weaker, and they develop immune complications into adulthood.
Exactly how LBW explains inadequate immunity is unknown. Using mouse models of abnormal placentation, we want to understand: i) how LBW impacts on immune function in neonates; ii) how the healthy adult immune system is ‘programmed’ during gestation.
The successful candidate will use high-dimensional flow cytometry to phenotype a large number of immune cells ex vivo. Immunoassays and gene expression will reveal information about the immune cell functions. Other techniques, e.g. immunohistochemistry, stereological techniques and confocal microscopy will also be used.
For further information, please contact Dr Jens Kieckbusch.
Barker, D.J. (2004). The developmental origins of well-being. Philos Trans R Soc Lond B Biol Sci 359, 1359-1366.
Colucci, F., and Kieckbusch, J. (2015). Maternal uterine natural killer cells nurture fetal growth: in medio stat virtus. Trends Mol Med 21, 60-67.
PrabhuDas, M., Adkins, B., Gans, H., King, C., Levy, O., Ramilo, O., and Siegrist, C.A. (2011). Challenges in infant immunity: implications for responses to infection and vaccines. Nat Immunol 12, 189-194.