Relevance of positive selection on human salivary amylase gene
人唾液淀粉酶基因正选择的相关性
基本信息
- 批准号:1810060
- 负责人:
- 金额:$ 14.8万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Standard Grant
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-09-15 至 2021-02-28
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
This award was provided as part of NSF's Social, Behavioral and Economic Sciences Postdoctoral Research Fellowships (SPRF) program. The goal of the SPRF program is to prepare promising, early career doctoral-level scientists for scientific careers in academia, industry or private sector, and government. SPRF awards involve two years of training under the sponsorship of established scientists and encourage Postdoctoral Fellows to perform independent research. NSF seeks to promote the participation of scientists from all segments of the scientific community, including those from underrepresented groups, in its research programs and activities; the postdoctoral period is considered to be an important level of professional development in attaining this goal. Each Postdoctoral Fellow must address important scientific questions that advance their respective disciplinary fields. Under the sponsorship of Dr. Alyssa Crittenden at University of Nevada, Las Vegas, this postdoctoral fellowship award supports an early career scientist investigating the impact of positive selection for increased copy number of the salivary amylase gene (AMY1) on the ability for humans to digest starch during the oral phase of food consumption. This project tackles unanswered questions regarding the significance of salivary alpha amylase (sAA) for starch consumption. Oral activity of sAA is the first step towards digestion of starchy foods. Yet humans have removed the need for oral digestion by externalizing food degradation through cooking, which breaks down large molecules such as starch. However it is unknown whether sAA activity during chewing is relevant for humans to digest starch. Importantly, no research exists that explores rate variation of sAA activity on raw versus cooked starch. Humans uniquely possess multiple copy numbers of AMY1, signaling a shift in dietary intake of starch. Such dietary shifts impact human health as it relates to tolerance of starch-rich diets. This project will contribute towards an understanding of human sAA genetic adaptations. Furthermore, understanding the impact of AMY1 variation on nutritional acquisition among ethnically and geographically diverse human populations helps inform dietary therapeutic strategies for metabolic disease prevention. This project uses a multidisciplinary approach to answer open questions about how dietary adaptation impacts health. The proposed research has three phases - an in-vitro modeling phase, a human participant trial phase, and a field work phase. Phase I will investigate starch digestion from exposure to sAA as a function of AMY1 copy number by measuring the reducing sugar byproducts across varying short time intervals. Histological assays will show sAA activity via the morphological changes to starch. Phase II will investigate oral starch digestion in human participants over short time intervals via oral manipulation of a starch solution. The expelled solution will similarly be measured for reducing sugars. Enzyme quantity will be measured on stimulated saliva using an ELISA kit for Amylase Alpha 1, and gene copy number will be measured using digital PCR against a reference single copy gene using DNA extracted from buccal swabs. These data will be combined with medical and dietary history data to help discover factors that influence the production and activity of sAA. Phase III entails field work to quantify chewing time allocated for orally processing starchy foods. These are valuable data to contextualize chewing for humans that subsist from foods that have not undergone extensive mechanical or thermal processing.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
该奖项是作为NSF的社会,行为和经济科学博士后研究奖学金(SPRF)计划的一部分提供的。SPRF计划的目标是为学术界,工业或私营部门和政府的科学事业准备有前途的早期职业博士级科学家。SPRF的奖励包括在知名科学家的赞助下进行两年的培训,并鼓励博士后研究员进行独立研究。NSF致力于促进来自科学界各部门的科学家,包括来自代表性不足的群体的科学家参与其研究计划和活动;博士后期间被认为是实现这一目标的专业发展的重要水平。每个博士后研究员必须解决推进各自学科领域的重要科学问题。在拉斯维加斯的内华达州大学的Alyssa Crittenden博士的赞助下,该博士后奖学金支持早期职业科学家调查唾液淀粉酶基因(AMY 1)拷贝数增加对人类在食物消耗的口服阶段消化淀粉的能力的影响。这个项目解决了关于唾液α淀粉酶(sAA)对淀粉消耗的重要性的悬而未决的问题。sAA的口服活性是消化淀粉类食物的第一步。然而,人类已经通过烹饪将食物降解外化,从而消除了口服消化的需要,烹饪分解了淀粉等大分子。然而,尚不清楚咀嚼期间的sAA活性是否与人类消化淀粉有关。重要的是,没有研究存在,探讨生淀粉与熟淀粉的sAA活性的变化率。人类独特地拥有AMY 1的多个拷贝数,标志着膳食淀粉摄入量的变化。这种饮食变化影响人类健康,因为它涉及对富含淀粉的饮食的耐受性。该项目将有助于了解人类sAA遗传适应。此外,了解AMY 1变异对不同种族和地理位置人群营养获取的影响有助于为代谢疾病预防提供饮食治疗策略。该项目使用多学科方法来回答有关饮食适应如何影响健康的开放性问题。 拟议的研究有三个阶段-体外建模阶段,人类参与试验阶段和实地工作阶段。第一阶段将研究淀粉消化暴露于sAA作为AMY 1拷贝数的函数,通过测量不同的短时间间隔内的还原糖副产物。组织学测定将通过淀粉的形态学变化显示sAA活性。第二阶段将研究人类参与者通过口服淀粉溶液在短时间间隔内的口服淀粉消化。将类似地测量排出的溶液的还原糖。将使用淀粉酶α 1的ELISA试剂盒测量刺激唾液中的酶量,并使用从口腔拭子中提取的DNA,使用数字PCR针对参考单拷贝基因测量基因拷贝数。这些数据将与医疗和饮食史数据相结合,以帮助发现影响sAA产生和活动的因素。第三阶段需要进行实地工作,以量化分配给口服加工淀粉类食物的咀嚼时间。这些都是有价值的数据,以背景下咀嚼人类的食物,没有经过广泛的机械或热加工。这个奖项反映了NSF的法定使命,并已被认为是值得支持的评估使用基金会的智力价值和更广泛的影响审查标准。
项目成果
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