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NSF Postdoctoral Fellowship in Biology FY 2017: Elucidating the role of enhancers in hominid craniofacial evolution and diseases

2017 财年 NSF 生物学博士后奖学金：阐明增强子在原始人类颅面进化和疾病中的作用

基本信息

批准号：
1711847
负责人：
Jaaved Mohammed
金额：
$ 20.7万
依托单位：
Mohammed Jaaved
依托单位国家：
美国
项目类别：
Fellowship Award
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-01 至 2021-06-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1711847&HistoricalAwards=false
关键词：
NSF Postdoctoral Fellowship Biology FY

项目摘要

This is an NSF Postdoctoral Research Fellowship in Biology, under the program Broadening Participation of Groups Under-represented in Biology. The fellow, Jaaved Mohammed, is conducting research and receiving training that is increasing the participation of groups underrepresented in biology. The fellow is being mentored by Dr. Joanna Wysocka at Stanford University. The goal of this research project is to characterize craniofacial mutations (those of the head and face), and to understand their impact at the molecular level. The head and face are remarkably distinctive organs that set humans apart from each other and from other species. Enhancers are a class of DNA elements that play important roles in craniofacial differences, yet mutations in enhancer sequences that underlie these differences remain poorly understood. This research project will benefit the scientific community, the general public, and individuals underrepresented in science and technology. First, the basic biology knowledge gained from this proposed work will be disseminated to audiences of varied technical expertise via journal articles, conferences, and print and social media. Second, this research will produce a database of DNA mutations that may be implicated in craniofacial disorders. Third, the proposed research will help our society learn about our distant ancestry. Specifically, it will address how DNA of Neanderthal origin, introduced into the genome of modern humans when our ancestors and Neanderthals interbred in ancient Eurasia, led to beneficial human adaptations and our increased risk of diseases. Finally, the fellow will mentor students underrepresented in science and technology in his research lab. To characterize nucleotide differences within enhancers that contribute to craniofacial differences across hominids via regulation of transcription factor binding, epigenetic modifications, and gene expression, the fellow will utilize Cranial Neural Crest Cells (CNCCs) and the Neanderthal genome. CNCCs are a relevant model for addressing this goal because CNCC derivatives become the embryonic face. Furthermore, the recent availability of the Neanderthal genome facilitates the study of human morphology and traits at a finer resolution, than comparisons to the chimpanzee. Using these systems, the fellow will employ an interdisciplinary strategy to identify enhancers that have evolved adaptively, to quantify the potency of enhancer variants on transcription exogenously, and to understand the effect of Neanderthal enhancers on CNCC behavior, and ultimately, morphology.

这是NSF生物学博士后研究奖学金，根据扩大生物学中代表性不足的群体的参与计划。这位名叫Jaaved Mohammed的研究员正在进行研究并接受培训，以增加生物学中代表性不足的群体的参与。这位研究员正在接受斯坦福大学乔安娜·威索卡博士的指导。该研究项目的目标是描述颅面突变（头部和面部的突变），并在分子水平上了解其影响。头和脸是非常独特的器官，使人类彼此之间以及与其他物种区分开来。增强子是一类在颅面差异中发挥重要作用的DNA元件，但对这些差异背后的增强子序列突变仍知之甚少。该研究项目将使科学界、公众和在科学和技术领域代表性不足的个人受益。首先，从这项拟议工作中获得的基本生物学知识将通过期刊文章、会议、印刷和社交媒体传播给具有不同技术专长的受众。其次，这项研究将产生一个可能与颅面疾病有关的DNA突变数据库。第三，拟议中的研究将有助于我们的社会了解我们的远祖。具体来说，它将解决当我们的祖先和尼安德特人在古代欧亚大陆杂交时，如何将尼安德特人起源的DNA引入现代人类的基因组中，导致有益的人类适应和疾病风险增加。最后，这位研究员将在他的研究实验室指导科学和技术领域代表性不足的学生。为了表征增强子内的核苷酸差异，这些差异通过调节转录因子结合，表观遗传修饰和基因表达来促进原始人类的颅面差异，该研究员将利用颅神经嵴细胞（CNCC）和尼安德特人基因组。CNCC是实现这一目标的相关模型，因为CNCC衍生物成为胚胎面孔。此外，最近尼安德特人基因组的可用性有助于以更精细的分辨率研究人类形态和特征，而不是与黑猩猩进行比较。使用这些系统，该研究员将采用跨学科的策略来识别自适应进化的增强子，量化增强子变体对外源转录的效力，并了解尼安德特人增强子对CNCC行为的影响，最终，形态。