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

这是NSF生物学博士后研究奖学金，在该计划下，扩大了生物学中代表性不足的群体的参与。这位名叫贾维德·穆罕默德(Jaaved Mohammed)的研究员正在进行研究和接受培训，这将增加生物学中代表性较低的群体的参与。斯坦福大学的乔安娜·维索卡博士对他进行了指导。这个研究项目的目标是描述颅面突变(头部和面部的突变)的特征，并在分子水平上了解它们的影响。头和脸是非常独特的器官，使人类彼此区别开来，也区别于其他物种。增强子是一类在头面部差异中发挥重要作用的DNA元件，但这些差异背后的增强子序列突变仍然知之甚少。这项研究项目将使科学界、普通公众和在科学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、会议以及印刷和社交媒体向不同技术专长的受众传播。其次，这项研究将产生一个可能与头面部疾病有关的DNA突变数据库。第三，这项拟议的研究将帮助我们的社会了解我们的远古祖先。具体地说，它将阐述当我们的祖先和尼安德特人在古代欧亚大陆杂交时被引入现代人基因组的尼安德特人起源的DNA如何导致有益的人类适应和我们疾病风险的增加。最后，这位研究员将在他的研究实验室指导在科学和技术领域代表性不足的学生。为了通过调节转录因子结合、表观遗传修饰和基因表达来表征增强子中导致原始人头面部差异的核苷酸差异，该研究员将利用脑神经脊细胞(CNCC)和尼安德特人的基因组。CNCC是解决这一目标的相关模式，因为CNCC衍生品成为胚胎面孔。此外，最近尼安德特人基因组的出现有助于以更高的分辨率研究人类的形态和特征，而不是与黑猩猩进行比较。利用这些系统，该研究员将采用跨学科策略来识别适应性进化的增强子，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，并最终了解形态。

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.