Identifying the radioprotective potential of radiation-resistant fungi using Drosophila - PROJECT SUMMARY:
Ionizing radiation causes double strand breaks and damages the protein-based mechanisms responsible for
their repair. This makes mitotic cells in the bone marrow, gut and reproductive organs highly susceptible to
ionizing radiation damage. In addition, as humans age, we become more susceptible to the effects of radiation
likely due to inherent accumulated cellular damage we accrue over time. There are very few pharmaceutical
countermeasures approved for mitigation of acute radiation damage, and none are effective for prophylactic
intervention. Given the use of nuclear power plants, the proliferation of nuclear arms and increased global
interest in space flight with its concomitant cosmic ray exposure, there is a pressing need to identify medicinal
sources of radioprophylactics.
Fungi are sources of diverse and powerful pharmaceuticals, and many strains of fungi are remarkably
radioresistant. Various fungi have been found growing in the heavily irradiated environments of the Chernobyl
Nuclear Power Plant and the International Space Station. To meet the growing need for radioprophylactics, we
seek to determine the radioprotective efficacy of dietary administration of highly radiation-resistant non-
pathogenic fungi. Drosophila are natural fungivores. In addition, Drosophila are an excellent model system in
which to study the damaging effect of radiation exposure on various organ systems since they share many
similarities with vertebrates yet are easily manipulated with sophisticated genetics and cell biology. We
hypothesize that consumption of these fungal strains will increase resistance to acute radiation damage
through known and unidentified factors. To do this, we will feed three Drosophila genotypes a panel of highly
radioresistant fungi. In addition to wild type flies, we will also test whether radioresistant fungi confer
radiation resistance to two mutant Drosophila strains that accumulate oxidative damage. To test our
hypothesis, we propose a single Aim. We will exposure the flies to gamma irradiation and test if the selected
dietary fungi confer radioprotection to lifespan, the gastrointestinal tract, the ovary, and various biomolecules.
We expect to find a radioprotective effect of dietary radioresistant fungi at one or several levels of our studies
from organismal to molecular. Knowledge gained from this research will open the opportunity to screen
hundreds of fungi using a relatively simple method. Once protective fungal strains are identified, future studies
can test their effectiveness in vertebrates, as well as identify the molecules responsible.
