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

这是美国国家科学基金会生物学博士后研究奖学金，隶属于“扩大生物学中代表性不足群体的参与”项目。这位名叫贾韦德·穆罕默德（Jaaved Mohammed）的研究员正在进行研究并接受培训，以增加在生物学中代表性不足的群体的参与。他的导师是斯坦福大学的Joanna Wysocka博士。本研究项目的目标是表征颅面突变（头部和面部的突变），并了解其在分子水平上的影响。头和脸是非常独特的器官，使人类与其他物种区别开来。增强子是一类在颅面差异中起重要作用的DNA元件，然而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、公众和在科学技术领域未被充分代表的个人受益。首先，从这项提议的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各种技术专业知识的受众。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，拟议的研究将有助于我们的社会了解我们遥远的祖先。具体来说，它将讨论当我们的祖先和尼安德特人在古代欧亚大陆杂交时，尼安德特人的DNA是如何被引入现代人的基因组的，这导致了有益的人类适应和我们患病风险的增加。最后，该研究员将在其研究实验室指导在科学和技术方面代表性不足的学生。为了通过转录因子结合、表观遗传修饰和基因表达的调节来表征促进古人类颅面差异的增强子内的核苷酸差异，该研究员将利用颅神经嵴细胞（cncc）和尼安德特人基因组。CNCC是解决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。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，并最终对形态学的影响。

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.