Award Abstract # 2233251
BRC-BIO: Analyzing the role of Drosophila variant Polycomb Repressive Complexes in developmental gene transcription

NSF Org: DBI
Division of Biological Infrastructure
Recipient: EMMANUEL COLLEGE
Initial Amendment Date: February 22, 2023
Latest Amendment Date: February 22, 2023
Award Number: 2233251
Award Instrument: Standard Grant
Program Manager: Bianca Garner
DBI
 Division of Biological Infrastructure
BIO
 Directorate for Biological Sciences
Start Date: June 1, 2023
End Date: May 31, 2026 (Estimated)
Total Intended Award Amount: $447,650.00
Total Awarded Amount to Date: $447,650.00
Funds Obligated to Date: FY 2023 = $447,650.00
History of Investigator:
  • Janel Cabrera (Principal Investigator)
    cabreraj2@emmanuel.edu
Recipient Sponsored Research Office: Emmanuel College
400 FENWAY
BOSTON
MA  US  02115-5725
(617)735-9979
Sponsor Congressional District: 07
Primary Place of Performance: Emmanuel College
400 FENWAY
BOSTON
MA  US  02115-5725
Primary Place of Performance
Congressional District:
07
Unique Entity Identifier (UEI): VGK6JK18ZKQ5
Parent UEI: VGK6JK18ZKQ5
NSF Program(s): NFE-New Faculty Enhancement
Primary Program Source: 01002324DB NSF RESEARCH & RELATED ACTIVIT
Program Reference Code(s): 7465
Program Element Code(s): 202Y00
Award Agency Code: 4900
Fund Agency Code: 4900
Assistance Listing Number(s): 47.074

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.

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