Genomic Imprinting and the regulation of postnatal nutritional resources via breastmilk

从母亲到婴儿的营养控制对后代的终身健康和幸福至关重要。我们的提案旨在了解规范成功母乳喂养的关键机制，特别是母乳的正常生产和确保其含量最有利于哺育婴儿的过程。我们研究了一组特殊的基因，称为“印记基因”，已知这些基因对调节婴儿及其胎盘的产前生长很重要。来自我们自己和其他人的证据表明，这些基因还调控着出生后的重要过程，包括母乳喂养，但人们对印记基因在出生后营养控制中的功能知之甚少。我们的第一个目标是解决印记基因的蛋白质产物在母乳中的存在程度，无论是在婴儿出生后第一次摄入的液体中，还是在婴儿稍大一点的后来的牛奶中。随着时间的推移，我们将对牛奶中的这些蛋白质进行量化。这是理解作为一个过程的印记是否可以帮助婴儿正常成长的重要第一步，并可能对终身健康和无法茁壮成长的婴儿产生影响。在我们的第二个目标中，我们将应用我们目前对乳腺中负责产奶的细胞的知识，并研究在怀孕和哺乳期间这些特定类型的乳腺细胞发生的发育变化。这将有助于我们理解牛奶蛋白质的生产过程。这种对印记基因产物调控的更详细的分析也可能为印记过程的功能和进化提供有用的基本见解。我们的第三个目标是研究印记基因的蛋白质产物对后代成功生长和发育的重要性。我们将检查这些蛋白质产品的存在如何影响新生儿的正常和不正常的生长，以及它们是否对他们的终身健康有任何长期影响，例如他们患肥胖症和糖尿病的风险，这些疾病已知可以通过母乳喂养来减少。这项计划的主要目标是了解牛奶中印记蛋白的重要性，它们如何调节子宫外的生长和发育，以及这方面的营养控制对早期健康和疾病起源的影响。

The control of nutritional from mother to her baby is essential for the lifelong health and wellbeing of offspring. Our proposal aims to understand key mechanisms that regulate successful breastfeeding; in particular the normal production of breastmilk and the processes ensuring that its content is optimum for supporting the baby. We study a particular set of genes called 'imprinted genes' that are known to be important for regulating prenatal growth of the baby and its placenta. Evidence from ourselves and others has suggested that these genes also regulate important processes after birth, including breastfeeding, but very little is known about the function of imprinted genes in postnatal nutritional control. Our first aim is designed to address the extent to which the protein products from imprinted genes can be found in breastmilk, both in the first fluid consumed by the baby after it is born, and in later milk once it is a little older. We will quantify these proteins in milk over time. This is important first step in understanding if imprinting as a process can help babies grow properly, and may have implications for lifelong health and for babies failing to thrive. In our second aim, we will apply our current knowledge on the cells in the mammary gland which are responsible for milk production and study the developmental changes occurring in these specific cell types of the mammary gland during pregnancy and lactation. This will contribute to our understanding of the production of milk proteins. This more detailed analysis on the regulation of imprinted gene products might also provide useful fundamental insights into the function and evolution of the imprinting process.Our third aim is to study the importance of the protein products of imprinted genes to the successful growth and development of the offspring. We will check how the presence of these protein products affect normal and abnormal growth of new-borns, and if they have any long-term effect on their life-long health for example on their risk to develop diseases such as obesity and diabetes which are known to be reduced by breastfeeding.The main goal of this programme is to understand the importance of imprinted proteins in the milk, how they regulate growth and development beyond the womb, and the influence of this aspect of nutritional control on the early origins of health and disease.