Investigation of Radiation Resistance Mechanisms in Melanized Fungi
Abstract
The ultimate goal of the project is to identify the most useful insight from research on fungal model organisms (melanized and non-melanized forms of the fungus Cryptococcus neofomans), which can be generalized to humans and subsequently translated to protection of soldiers from diverse sources of ionizing radiation. The research objective is to use multidisciplinary approaches and a variety of radiation types, over a broad range of doses and dose rates, to elucidate the mechanisms of melanin-mediated fungal radioresistance. We hypothesize that, beyond melanin and DNA repair machinery, other proteins, intracellular chemical species, organelles and regulatory networks, are involved in achieving the astounding radioresistance of many fungi. This project will involve transcriptomic, proteomic and metabolomic characterization of the cellular and molecular responses to radiation stresses, and identification of regulatory proteins and molecules which define the response to ionizing radiation. We will characterize the effects of radiation on major organelles and identify genes involved in radioresistance. We will determine the effects of radiation on electrochemical properties of fungal cells and identify reductants which enhance oxidation-reduction potential. We will construct mathematical models of the major processes involved in fungal radioresistance and will apply them to mammalian cells. During the first year of the project we have performed the experiments which showed that melanin afforded protection against deuterons and X-rays two melanized fungi - fast-growing Cryptococcus neoformans and slow-growing Cryomyces antarcticus. The induced-repair model described the survival data for both fungi better than the simpler linear-quadratic model. Deuteron and x-ray radiation resulted in metabolic activity increase for melanized fungal cells, while the activity of non-melanized cells remained the same or decreased. Our data suggest that melanin is protective not only against sparsely-ionizing photons, but also against densely-ionizing charged particles. These observations are important for creating melanin-based radioprotectors for soldiers on the battlefield. Such radioprotectors could also be used for cancer patients undergoing radiation therapy for cancer and for protection of the astronauts during the space flights.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- May 26, 2016
- Source ID
- HDTRA11510058
Entities
People
- Ekaterina Dadachova
Organizations
- Albert Einstein College of Medicine
- Defense Threat Reduction Agency