Professor Tom Leonard's research
The ability to see similarities in apparently unrelated events can lead a microbiologist like
Tom Leonard
down a path of discovery. One day, completely by accident, Leonard noticed what appeared to be
abnormal growths on a common fungus. The growths, which Leonard called "mounds," reminded him of
plant and animal tumors. Leonard knew that scientists are still uncertain about the mechanism that
causes cells to multiply out of control, creating tumors that impair the functioning of healthy
organs and tissue. Could research into these puzzling fungal mounds provide clues to the growth
of tumors in the human body? Leonard and his team decided to investigate.
Read below about Leonard's research (with colleague Stanley Dick) into the developmental
expression of the mound gene, or go to an online interview
with graduate student Nora Mineva and undergraduate Julie Mazeika '03 to learn more about their
attempts to isolate and identify the gene responsible for causing mounds.
Schizophyllum commune is the scientific name for the fungus in which Leonard first observed
abnormal growths. He noted that the mounds could be distributed on the surface of the fungal
colony, but could also be growing from the reproductive structures themselves. (Non-scientists
call these reproductive structures mushrooms.) Leonard could see that the mounds often overgrew
the mushrooms and prevented them from releasing spores that produce the future generation of
fungus.
S. commune is one of the most common fungi in the world, known to naturalists as the split
gill mushroom. Often found growing on dead tree branches, its role in the ecosystem is to help
decompose dead plant material. Like most fungi, s. commune is multi-cellular, consisting
of networks (mycelia) of long, slender strands of cells called hyphae. Some of the hyphae
penetrate decaying organic matter and extract nutrients to feed the fungus. Other hyphae form
the tightly packed shapes we call mushrooms. A fungus, like the human body, grows by having cells
make copies of themselves.
By comparing cells from mounds with those from "normal" parts of the fungus, Leonard discovered
two things. He learned that a growth-controlling gene is responsible for mound formation in
s. commune. He also realized that one of the two nuclei in a normal hyphal cell* often
contained the mound gene. As long as only one nucleus contained the mound gene the cell would
replicate normally. However, if both nuclei in the cell contained the mound gene,
then the cell's offspring would develop into rapidly growing mounds.
The mystery of mounds lies in how cells containing one mound gene and one normal gene give
rise to new cells containing two mound genes. When hyphal cells replicate (see
animation),
they are supposed to make exact copies of themselves. The mechanism is still uncertain, but
Leonard and Dick speculate that somehow the mound gene in one nucleus "communicates" with the
"normal" gene in the other nucleus, resulting in a new cell in which both nuclei contain the
mutant gene. Leonard and Dick noted that abnormal mounds seem more likely to arise in areas of
older hyphae.
Leonard and his team are now attempting to isolate the mutant mound gene so that it may be
characterized and compared to gene sequences identified in the human genome project, where
any sequences associated with uncontrolled cell division would be of general interest.
*There are two kinds of hyphae cells in s. commune: those with one nucleus (monokaryons)
and those with two nuclei (dikaryons), based on the number of nuclei per hyphal cell. A dikaryon
forms as a result of hyphal fusion between two compatible monokaryons.
A mutant strain of the fungus being grown in the lab. Note the mounds indicating out-of-control cell growth.
A wildtype (normal) strain being grown in the lab.
The result of a cross between the wildtype and mutant strains.
