BRC-BIO: analyzing the role of drosophila variant polycomb repressive complexes in developmental gene transcription

This three-year, $447,650 project grant from the National Science Foundation's Biological Sciences program (CFDA 47.074) will fund research at Emmanuel College analyzing the role of variant polycomb repressive complexes in developmental gene transcription in Drosophila. Undergraduate researchers will use genetic, molecular, and biochemical techniques to characterize a variant PRC1 complex and its role in coordinating cell-type specific transcription critical for normal development. Insights gained into the mechanism of this complex's developmental gene regulation in Drosophila may inform studies of mammalian development. The award also aims to increase participation of underrepresented ethnic and racial groups in undergraduate research experiences at Emmanuel College and collaboration with researchers at Harvard Medical School and Brandeis University.

Abstract

Multicellular organisms are composed of individual cells that function distinctly, due to the regulation of gene expression during development. Developmental gene regulation is largely made possible by many protein complexes that turn genes on or off at appropriate developmental windows. An important example is the polycomb repressive complex, which turns off a specific set of developmental genes. How this complex selects the correct genes to silence during early development is still unknown. This project will utilize the fruit fly as model organism to study the role of this silencing complex in orchestrating developmental gene expression. Discovering the mechanism by which polycomb repressive complexes silence genes in the fruit fly will inform our understanding of development in mammals. Another significant goal of this project is to increase the participation of persons traditionally excluded because of their ethnicity or race (peers) in undergraduate research experiences at emmanuel college. Student researchers will use genetic, molecular, and biochemical techniques to address the aims of this project. Collaborations with researchers from harvard medical school and brandeis university will facilitate engagement of peer undergraduate students with the broader scientific community. The goal is to inspire larger numbers of peer students to pursue careers in stem. Multicellular development is governed by the deployment of cell-type specific transcriptional programming, in which a single genome is utilized distinctly over time and space as cells multiply and specialize. This phenomenon is achieved by the precise coordination of gene expression that initiates the differentiation of the different cell types of an organism. Chromatin regulatory factors have been found to be essential for regulation of developmental transcriptional programming however the mechanism behind how these factors coordinate gene expression during embryonic development remains unclear. One highly conserved chromatin regulatory system that plays a central role in developmental patterning and cell differentiation includes the polycomb group (PCG) proteins. These proteins are typically found in two distinct types of polycomb repressive complexes (prcs): PRC1 and PRC2. The PI's lab recently identified variant PRC1 (VPRC1) complexes in drosophila that have strong modular conservation with mammalian complexes, suggesting an ancient functional diversity. The goal of this work is to understand the role of VPRC1 complexes in coordinating the cell-type specific transcription critical for normal development. In this project, undergraduate student scientists will functionally characterize one of the VPRC1 complexes using a variety of methods, including crosslinking, tandem affinity purification, and integrated analysis of protein partners and DNA binding sites, in parallel with functional genetic approaches to dissect the changes in protein complexes during normal development in drosophila. Successful completion of this proposal will provide mechanistic details for function of a variant PRC1 complex in developmental gene regulation. Resulting insights will prove useful for future analyses in mammalian cells. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the foundation's intellectual merit and broader impacts review criteria.