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福祉至关重要。我们的建议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内容最适合支持婴儿的过程。我们研究了一组被称为“印记基因”的特殊基因，这些基因对调节婴儿及其胎盘的产前生长非常重要。来自我们和其他人的证据表明，这些基因也调节出生后的重要过程，包括母乳喂养，但对印迹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来自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摄入的第一种液体中，还是在婴儿稍大一点的牛奶中。我们将随着时间的推移对牛奶中的这些蛋白质进行定量。这是理解印记作为一个过程是否可以帮助婴儿正常成长的重要的第一步，并且可能对终身健康和婴儿无法茁壮成长产生影响。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了解，并研究妊娠和哺乳期间乳腺这些特定细胞类型中发生的发育变化。这将有助于我们了解牛奶蛋白质的生产。对印迹基因产物调控的详细分析也为印迹过程的功能和进化提供了有益的基础性认识。我们的第三个目的是研究印迹基因的蛋白产物对后代成功生长发育的重要性。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，例如他们患肥胖和糖尿病等疾病的风险，这些疾病已知可以通过母乳喂养来减少。该计划的主要目标是了解牛奶中印迹蛋白的重要性，它们如何调节子宫外的生长和发育，以及营养控制的这一方面对健康和疾病的早期起源的影响。

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.