A central question in mammalian biology is how identical DNA present in an organism creates diverse cell lineages. With this award, the Molecular and Cellular Biosciences of the National Science Foundation (NSF) is funding Professor Kabirul Islam, assistant professor in the Dietrich School's Department of Chemistry, to develop an integrated chemical biology research and educational program that aims to answer this very fundamental biological question.
Key to the cellular diversity in a multicellular organism like humans is the heritable changes in gene expression, primarily mediated by chemical modifications on DNA and its packaging materials called histones. In this project, the Islam group will study a specific modification called lysine methylation and its demethylases. The proposed work is focused on developing a novel chemical-genetic platform that combines pharmacological and genetic engineering to perturb specific isoforms of demethylase with rationally designed small molecules. Furthermore, the specificity and temporal control of the engineered demethylation apparatus will be combined with the spatial selectivity of programmable nucleases to develop a ‘first of its kind’ conditional epigenome-editing tool for regulating gene transcription at precise a space and time in intact cells. The approach will be subsequently employed to reprogram expression of genes that underlie faithful cell division, cellular differentiation, lineage commitment, and ultimately, organismal development.
The interdisciplinary research setting that brings together organic synthesis, protein engineering and cell biology, will provide a unique training ground for graduate and undergraduate students. Furthermore, a chemical biology laboratory course is designed to engage undergraduate students in an inquiry-based laboratory exercises where students will learn how carefully designed experiments can lead to the discovery of new scientific knowledge, thus encouraging them to develop into critical thinkers and independent learners. Early implementation of such a research-based course is expected to bridge a gap existing in the current curriculum and motivate STEM students in science education and research.