It is well established that the risk of adult obesity and other associated metabolic disorders can be programmed by intrauterine and early postnatal environment (1). Data from studies using animal models of both maternal under- and over-nutrition support the theory of developmental origins of obesity. However it is not clear how maternal nutrition during pregnancy would affect the metabolic phenotype in the offspring. One potential mechanism is programmed alterations in the epigenetic status of hypothalamic genes. We have shown that periconceptional maternal under-nutrition causes epigenetic changes in the regions in the brain that control energy balance (2, 3 & 4)
The aim of this project is to determine whether maternal high fat feeding during pregnancy causes epigenetic changes in brain appetite controlling pathways in the offspring. This will be achieved using rodent models of maternal over-nutrition during pregnancy, and assessment of the metabolic phenotype of offspring in later life. We will investigate the expression levels and epigenetic modifications of genes regulating feeding, satiety and energy expenditure.
Molecular tools will include qPCR, DNA methylation analysis by pyrosequencing and chromatin immunoprecipitation. Overall, this project will gain a better understanding of the mechanisms by which maternal over-nutrition can alter the regulation of food intake and energy balance in subsequent generations.
The successful candidate will be trained in a wide range of techniques. The in vivo techniques will include measurement of metabolic parameters such as food intake, glucose and insulin. To underpin the results, molecular biology techniques including qRT-PCR, western blotting, pyrosequencing, and chromatin immunoprecipitation will be used.
Candidates are expected to hold a minimum upper-second (or equivalent) undergraduate degree in a related biomedical/biological science. Previous laboratory experience is essential. A Masters qualification or relevant industrial laboratory experience would be an advantage.
This 3-year full-time PhD is open to candidates able to provide evidence of self-arranged funding/sponsorship and is due to commence from January 2017 onwards.
Any enquiries relating to the project and/or suitability should be directed to Professor White ([email protected]
). Applications are invited on an on-going basis but early expression of interest is encouraged.
This project has a Band 3 fee. Details of our different fee bands can be found on our website. For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website. Informal enquiries may be made directly to the primary supervisor.
1.Gali Ramamoorthy T, Begum G, Harno E, White A (2015) Developmental programming of hypothalamic neuronal circuits: impact on energy balance control. Front Neurosci 9:126
2.Stevens A, Begum G, Cook A, Connor K, Rumball C, Oliver M, Challis J, Bloomfield F, White A (2010) Epigenetic changes in the hypothalamic proopiomelanocortin and glucocorticoid receptor genes in the ovine fetus after periconceptional undernutrition. Endocrinology 151 (8):3652-64
3.Begum G, Stevens A, Smith EB, Connor K, Challis JR, Bloomfield F, White A (2012) Epigenetic changes in fetal hypothalamic energy regulating pathways are associated with maternal undernutrition and twinning. FASEB J 26(4):1694-703
4.Begum G, Davies A, Stevens A, Oliver M, Jaquiery A, Challis J, Harding J, Bloomfield F, White A (2013) Maternal undernutrition programs tissue-specific epigenetic changes in the glucocorticoid receptor in adult offspring. Endocrinology 154 (12):4560-9