Deciphering the function of naturally occurring peptides in human milk

破译母乳中天然存在的肽的功能

基本信息

批准号：
9144551
负责人：
David Charles Dallas
金额：
$ 24.9万
依托单位：
OREGON STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-01-01 至 2018-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9144551
关键词：
Adult Age Anti-Inflammatory Agents Anti-inflammatory Antibiotics Antifungal Agents Award Back Behavior Biological Biological Assay Blood Pressure Brain California Categories Circadian Rhythms Cleaved cell Collaborations Complex Digestion Doctor of Philosophy Eating Evolution Exhibits Faculty Food Fractionation Gastrointestinal tract structure Generations Goals Growth Head Health Human Human Milk Infant Infant Health Mammary gland Mass Spectrum Analysis Metabolism Methodology Milk Milk Proteins Modality Mothers Neonatal Intensive Care Units Nutritional Science Organ Outcome Ovulation Pancreas Peptide Hydrolases Peptide Signal Sequences Peptides Phase Positioning Attribute Postdoctoral Fellow Probiotics Property Proteins Research Research Project Grants Rest Role Sampling Signal Transduction Site Skin Specificity Stomach Structure System Techniques Testing Therapeutic Therapeutic Agents Time Universities Variant Work antimicrobial base commensal microbes design feeding food science health application immunoregulation in vitro Assay macromolecule medical schools novel pathogen pathogenic bacteria prebiotics programs protein aminoacid sequence tenure track

项目摘要

DESCRIPTION (provided by applicant): Peptides form the majority of signaling systems in humans. These peptides, produced in the gut, brain, pancreas, skin and other organs have far-reaching effects-controlling food intake, metabolism, blood pressure, behavior, ovulation, and circadian rhythms as examples. These signaling peptides have, in many cases, common modalities traceable back hundreds of millions of years in evolution. However, the application of peptides as therapeutic signaling agents has not been fully explored. We have shown, through novel mass spectrometry-based peptidomics methodology, that over 500 peptides are produced in human milk within the mammary gland itself. These naturally occurring peptides represent a new class of food molecules that have as yet uncharacterized signaling functions within the mother and the infant. We have shown that over 10% are homologous to known peptides with antimicrobial and immunomodulatory functions. The rest have yet to be discovered functions. First generation assays have discovered that the peptides identified have antimicrobial actions-as an ensemble, these peptides inhibited the growth of several strains of pathogenic bacteria. The proposed research program will define the entire range of naturally occurring milk peptides, their diverse functions and also which specific sequences are responsible. Peptides will be examined for specific biological- context-relevant actions, including antimicrobial, antifungal, prebiotic, anti-parasitic and anti-inflammatory actions. Investigating milk's peptides will unlock dynamic and complex system of macromolecules that can be applied to infant and adult health. My long-term goal is to leverage a Nutrition or Food Science tenure-track faculty position at a tier-one research university to establish a high-impact research program in human health. I am convinced that the core of this research program will be designed to understand the effects of human milk on infant health, particularly from the perspective of digestion, and use this understanding to guide the nourishment and health of all ages. University of California, Davis, is the premier place to accomplish the aims of this proposal during the K99 phase of the award. The collaborators I have brought together during my Ph.D. and first year of post- doctoral work have made this project possible. UC Davis provides not only state-of-the-art analytical mass spectrometry in Dr. Lebrilla's and Dr. Barile's labs, but also the ability to obtain samples from te stomachs of infants through a collaboration with Dr. Mark Underwood, the head of the neonatal intensive care unit at the UC Davis Medical School. In addition, I have networked with a large number of collaborators to test the milk peptides for a variety of functions in assays.

描述（由申请人提供）：肽构成人类的大部分信号系统。这些在肠道、大脑、胰腺、皮肤和其他器官中产生的肽具有深远的影响——例如控制食物摄入、新陈代谢、血压、行为、排卵和昼夜节律。在许多情况下，这些信号肽具有可追溯到数亿年进化的共同模式。然而，肽作为治疗信号剂的应用尚未得到充分探索。我们通过基于质谱的新型肽组学方法证明，母乳中的乳腺本身产生了 500 多种肽。这些天然存在的肽代表了一类新的食物分子，它们在母亲和婴儿体内具有尚未表征的信号功能。我们已经证明，超过 10% 的肽与已知的具有抗菌和免疫调节功能的肽同源。其余的功能还有待发现。第一代检测发现，所鉴定的肽具有抗菌作用——作为一个整体，这些肽抑制了几种病原菌菌株的生长。拟议的研究计划将定义天然存在的乳肽的整个范围、它们的不同功能以及负责的特定序列。将检查肽的特定生物背景相关作用，包括抗菌、抗真菌、益生元、抗寄生虫和抗炎作用。研究牛奶中的肽将揭示动态且复杂的大分子系统，可应用于婴儿和成人的健康。我的长期目标是利用一级研究型大学的营养或食品科学终身教授职位，建立一个在人类健康领域具有高影响力的研究项目。我坚信，该研究计划的核心将旨在了解母乳对婴儿健康的影响，特别是从消化的角度，并利用这种理解来指导各个年龄段的营养和健康。加州大学戴维斯分校是在 K99 奖项阶段实现该提案目标的首要地点。我在攻读博士学位期间召集的合作者。第一年的博士后工作使这个项目成为可能。加州大学戴维斯分校不仅在 Lebrilla 博士和 Barile 博士的实验室中提供最先进的分析质谱仪，而且还能够通过与该实验室负责人 Mark Underwood 博士的合作从婴儿胃中获取样本。加州大学戴维斯分校医学院的新生儿重症监护室。此外，我还与大量合作者建立了联系，以在分析中测试牛奶肽的各种功能。