Analyses of the molecular mechanisms of HMT-1-dependent heavy metal detoxification CALS Impact Statement

This project seeks to use complementary biochemical and molecular genetic approaches in the nematode worm C. elegans to determine the mechanism of HMT-1-promoted heavy-metal detoxification. We will study the tissues and cell types involved in heavy-metal detoxification; ultrastructural consequences of cellular heavy-metal toxicity; metabolites and pathways functioning in heavy-metal detoxification, and biomarkers of heavy-metal toxicity.

Chronic exposure to heavy metals from the food chain and air leads to their accumulation in tissues and causes various disease states, such as damaged mental and central nervous function, slowly progressing neurological degenerative processes that mimic Alzheimer`s and Parkinson`s diseases, and dysfunction of lungs, kidneys, liver, and other vital organs, and can lead to cancer. This project has been initiated because I discovered that an ATP-binding cassette transporter from C. elegans, CeHMT-1, is absolutely required for heavy metal detoxification and that it is conserved in higher animals and humans. In addition, I discovered that CeHMT-1 is expressed in head neurons, coelomocytes (primitive liver cells), and intestinal cells of C. elegans, tissues and cell types that are affected the most by heavy-metal toxicity. Recently, I received a call from a citizen, Bobbie Delory, who is diagnosed with the acute heavy-metal poisoning (http://www.ourtoxicstories.com/Bobbie_s_Story.html). She seeks alternative methods of treatment against heavy-metal poisoning and turned to me for help. Her story shocked me and at the same time strengthened the significance of this research project, the ultimate goal of which is to contribute to developing new approaches for preventing and treating heavy-metal poisoning.

We are establishing molecular-biochemical procedures for analyses of mechanisms of the CeHMT-1-dependent pathway for heavy metal detoxification in C. elegans.

This project is still in its developmental stage. Therefore, it is too early to evaluate its impact on society.

Overview