All humans begin as a single cell that divides and eventually forms the complex structure of the human body. However, the process by which one cell gives rise to hundreds of different types in humans is largely a mystery to scientists.
Yukiko Yamashita, a research assistant professor at the University’s Life Sciences Institute, has been awarded a $500,000 W. M. Keck Foundation grant to study the biological processes behind cell division and differentiation. The organization is known in the scientific community for funding “high-risk, high-reward” research projects.
The grant will likely fund the next two years of research at Yamashita’s lab, where researchers aim to shed light on one of the most basic questions of modern biology: how genetically identical cells can develop different functions in the human body.
“When one cell becomes two, this is supposed to be an exact copying process, but then if you are exactly copying (the cells), we shouldn’t be us — (we’re) made of different kinds of cells,” Yamashita said.
“If (all cells) were just the same, you would just be 100 or 200 pounds of cell mass,” Yamashita continued. “But we are not … all of the cells in our body are different and know how to coordinate.”
The lab research hypothesizes the link to this cell differentiation lies within the cell’s genetic material — its DNA.
“Quite a bit of who you are is defined by what kind of gene combination you have, and this information is stored in DNA,” Yamashita said. “All DNA is like an encyclopedia, (it holds) everything about you — what kind of skin color, hair color or eye color — who you are.”
During cell replication, each new cell receives a copy of all the genetic information stored in the parent cell’s DNA.
When a parent cells undergoes cell division, it forms two genetically identical daughter cells. By studying stem cells from fruit flies, the lab has discovered slight differences between these daughter cells.
Yamashita said figuring out why cells adapt to different characteristics even though their DNA contents are indistinguishable has been a “fundamental mystery in biology.”
Yamashita’s lab has theorized that the different cell expressions are due, in part, to epigenetic markers on the cell’s DNA. These epigenetic markers can best be understood as “bookmarks” placed into the cell’s “instruction book,” which is the DNA molecule, Yamashita said. Different markers exist for skin, blood and other aspects of the body.
“Somehow (cells) distinguish (which bookmark to use) and segregate them into two,” Yamashita said. “This is the first direct evidence that cells are capable of distinguishing two same-DNA molecules.”
Using these “bookmarks,” human cells only express some of the genetic traits found in DNA. For example, skin cells do not develop the same neurotransmitters found in the brain, but instead express the pigment melanin, which creates skin color.
The genetic bookmarks are formed by a chemical process known as methylation. This process attaches a chemical group to the outside of the DNA molecule at a specific location, which usually suppresses the gene in that area.
“How much of the DNA is methylated — where it is methylated — affects where cells actually transcribe the genes — which genes to activate,” Yamashita said. “Cells somehow can distinguish which DNA copy is more methylated or less methylated.”
Despite the currently accumulated knowledge of cell division, Yamashita said more work must be done to determine the exact mechanisms by which these genetic processes take place.
“Our discovery only tells us cells can distinguish two DNA (molecules) that look the same, but are probably different,” Yamashita said. “We want to know … exactly how they are different.”
“This might answer this most fundamental question in biology — how we multicellular organisms, made of a hundred trillion cells, came from a single cell,” Yamashita said. “If you understand this, the implication is huge.”
These consequences include possible medical advancements. She added that his team hopes to use the long-lasting grant to get some concrete answers about cell division within two years.
“The fundamental understanding is always the basis of medical research,” Yamashita said. “If we contribute anything to the knowledge of fundamental biology … we can come up with ideas of how to cure (genetic diseases).”