The Center for Precision Environmental Health at Baylor College of Medicine is on a mission to discover new factors that explain and drive evolutionary change. This goal is shared by the John S. Templeton Foundation, which supports research that makes progress in understanding the deepest and most perplexing questions facing humankind.
Recognizing this common mission, Dr. Cheryl Lyn Walker, director of the Center, proposed a new idea to the Templeton Foundation: that a dual-function machinery that can respond to changes in the environment to coordinate functional changes in the cytoskeleton with heritable changes in the epigenome could drive evolution. To pursue this idea, Walker and her team have been awarded a three-year, $1.58 million grant from the Templeton Foundation.
The “software” of the epigenome is made up of small chemical modifications to the genome that specify which genes are turned on or off in various cells types, all of which have the same genome but must perform distinct functions in the body. This epigenetic software operates like computer software to direct the function of the genomic DNA “hardware,” which then directs the function of the genome in every living cell.
The Walker lab made a foundational discovery that the cell’s epigenetic machinery actually acts in two ways, not only directing the function of the genome, but also directing the function of the cell’s cytoskeleton. This new and unexpected discovery revealed that epigenetic machinery controls many key aspects of cell biology such as cell size, shape and movement, by acting directly on the cytoskeleton.
“We believe this dual-function machinery could act as a driver for evolution by coupling acquisition of new cytoskeletal functions with heritable changes in the epigenome, which we are terming Epigenetic Entrainment,” said Walker, who also is a professor in the Departments of Molecular and Cellular Biology, Medicine, and Molecular and Human Genetics at Baylor, and a member of its Dan L Duncan Comprehensive Cancer Center. “Previously, we were only aware of how the half of this machinery was responding to the environment by changing the epigenome. Now, we know it is also changing the function of the cell’s cytoskeleton, and potentially driving acquisition of new or adaptive functions. We want to know more about how this dual-function machinery may be coordinating changes in the epigenome with cytoskeletal changes to drive evolution.”
In other words, Walker explained, does this dual-function machinery respond to an environmental challenge, and provide a survival advantage, by coordinating adaptive changes in cytoskeletal function with changes in epigenetic memory, to drive evolution?
The key activities to be conducted by the research team are to identify the tools, or proteins, of the dual-function machinery that act on both the chromatin and the cytoskeleton, determine the rules of how these proteins act on both chromatin and the cytoskeleton, and test the hypothesis that, when perturbed by an environmental stimulus, coordinated and heritable changes are caused by this machinery on the epigenome and cytoskeleton.
The support from the Templeton Foundation also will provide an opportunity for Walker and the research team to integrate their theory of Epigenetic Entrainment into current evolutionary biology research through engagement with evolutionary biologists from around the world.
Collaborators on the project include Dr. David Reiner, with Texas A&M Health Science Center Institute of Biosciences and Technology, and Dr. Patrick Allard, with the University of California.