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

Mohammed Jaaved, Palo Alto CA

Investigators

Abstract

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.