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Centre for Trophoblast Research

 

Supervised by: Anne Ferguson-Smith (anne.fergusonsmith@admin.cam.ac.uk)(Geula Hanin, ghl35@cam.ac.uk) & Amanda Sferruzzi-Perri (ans48@cam.ac.uk)

Project Title

Investigating the role of imprinted genes in pre- and post-natal stages, and the links between maternal diet, placental signalling and lactation

Project description

The mammalian reproductive cycle encompasses pregnancy and lactation, which evolved to support the offspring and ensure their fitness and survival. As soon as the neonate is born, it is heavily dependent on maternal support and postnatal care, including lactation, a fundamental process enabling nutrient transfer to the neonate by the mammary gland delivering milk. 

Many studies have shown that breastfeeding is essential for offspring lifelong health both in the short-term by enabling organ growth, immunity, and microbial colonisation and in the longer-term by influencing the susceptibility to diseases such as obesity and diabetes through developmental programming.

Research shows that obese mothers are less likely to initiate lactation, have delayed lactogenesis, and are prone to early cessation of breastfeeding. The factors contributing to this association are poorly understood.

Genomic imprinting is a mammalian epigenetically regulated process causing genes to be expressed according to their parental origin. Many imprinted genes regulate growth and development in prenatal stages. However, recently, we found that imprinted genes are expressed in adult mouse mammary cells and that perturbing those genes affects the growth, development and health status of the offspring. 

Given the increasingly high rates of obesity among women of reproductive age and the importance of breastfeeding for offspring’s health, further work is required to understand the links between maternal obesogenic diet, placental signalling, lactation performance, and imprinted genes.

The study will address this key knowledge gap using mouse mutants where imprinted genes have been genetically altered, diets that induce obesity and a combination of physiological, molecular and histological approaches. The project will involve training in a variety of in vivo (e.g. genetic and dietary manipulation, metabolic assays, lactation tests, glucose/insulin tolerance tests, TdNMR scanning), molecular (e.g. RNAseq, western blotting) and histological (immunostaining, fluorescent and confocal microscopy, stereology) techniques. The student will also be trained in data statistical analysis and visualisation, and will spend time in both of the CTR group leader’s labs, to maximise skills training and knowledge acquisition.
The results of this study will provide critical scientific insights valuable for different fields and may help to shape policy on diet the impact of obesity and diet on maternal and child health worldwide.
 

References

  1. Rasmussen, K. M. (2007). Association of maternal obesity before conception with poor lactation performance. Annual review of nutrition, 27(1), 103-21
  2. Napso, T., Yong, H. E., Lopez-Tello, J., & Sferruzzi-Perri, A. N. (2018). The role of placental hormones in mediating maternal adaptations to support pregnancy and lactation. Frontiers in physiology, 9, 1091.‏
  3. Tucci, V., Isles, A. R., Kelsey, G., Ferguson-Smith, A. C., Bartolomei, M. S., Benvenisty, N., ... & Wilkins, J. (2019). Genomic imprinting and physiological processes in mammals. Cell, 176(5), 952-965
  4. Hanin, G., & Ferguson‐Smith, A. C. (2020). The evolution of genomic imprinting: Epigenetic control of mammary gland development and postnatal resource control. Wiley Interdisciplinary Reviews: Systems Biology and Medicine, 12(3), e1476
  5. Lean, S.C, Candia, A.A., Gulacsi, E., Lee, G.C.L., Sferruzzi-Perri, A.N (2022) Obesogenic diet in mice compromises maternal metabolic physiology and lactation ability leading to reductions in neonatal viability. Acta Physiologica e13816.  
     

Candidate background

Degree in a relevant biological science such as physiology, genetics or biochemistry

Image caption:  Whole mount image of a mammary gland during gestation, provided by Geula Hanin