Worcester Polytechnic Institute (WPI) researcher Amity Manning has been awarded a $1.1 million CAREER grant from the National Science Foundation (NSF) to determine the factors influencing a critical piece of cellular machinery during normal cell division.
The five-year project will focus specifically on histone modifications in a dividing cell and how they recruit proteins to help with the process of cell division. More broadly, the project will answer questions about a fundamental cellular process that impacts how organisms grow, mature, and maintain life.
"Proper cell division is critical for all living organisms," said Manning, assistant professor in the Department of Biology and Biotechnology. “Cell division, however, must be precise and accurate. Understanding the role of histone modifications in the equal division of genetic material when a cell divides is going to have implications for all normal processes that require cell proliferation.”
Manning will define the cellular mechanisms that enrich an enzyme called Suv420 on chromosomes, which are molecules in the cell nucleus that contain genetic code. Suv420 modifies a histone protein, H4K20me3, that is involved in organizing chromosomes. H4K20me3 is enriched on chromosomes near a central point called the centromere. Suv420 and H4K20me3 are thought to play a role in sorting chromosomes from a parent cell into new daughter cells and preventing chromosome sorting errors that could occur during cell division. Manning also will define the role that other histone modifications play in the composition and function of centromeres.
The project builds on Manning’s previous research exploring molecular mechanisms that regulate cell division. She is working to define the role of retinoblastoma protein in cell division errors and to help develop computational models that account for the forces that influence cell division.
Cell division, also known as mitosis, is a complex process in which a parent cell that has already duplicated its genome splits the genetic material equally into two new daughter cells, each with a copy of genetic code from the parent cell. Much about the process, and how it can go wrong, remains unknown, and greater understanding of the process could have implications for human health research.
“We know that there can be defects in the cell division process, and that those defects lead to cells that are genetically different from the parent cell,” Manning said. “Genetically different cells are a factor in cancer, antibiotic-resistant bacteria, and miscarriages. A greater understanding of the basic science of mitosis could have implications for any disease that involves cell proliferation.”
As part of the project, Manning will add material to her undergraduate biology courses to enhance scientific literacy among students, and she will participate in co-op and internship programs for high-school students that are aimed at encouraging underrepresented populations to pursue careers in science.