PgmNr W4086: Determining the Role of DBL-1 TGF-β Signaling in the Response to Potential Therapeutic Compounds in the C. elegans Model System.

Authors:
G. Ravindranathan 1 ; R. A. Veettil 1 ; A. Gekombe 1 ; S. Ghosh 2 ; D. Dolliver 3 ; D. Hynds 1 ; M. Bergel 1 ; T. L. Gumienny 1


Institutes
1) Texas Woman's University, Denton, TX; 2) Southeast Missouri State University, Cape Girardeau, MO; 3) Southeastern Louisiana University, Hammond, LA.


Keyword: Stress response

Abstract:

Development of therapeutic drugs is a challenging and lengthy process. It is vital to understand the reactions of the system being treated — both intended and side effects — and the best dosage for maximum efficacy with minimum side effects or long-term effects. Due to the complexity of human systems and ethical issues, the effect of a drug/compound cannot be directly tested without pre-clinical trials. C. elegans is an animal system for testing the toxicity of candidate compounds, and can provide preliminary data to justify the time, effort, and expense of pre-clinical studies in vertebrate models. We predict that C. elegans responds to toxic compounds using a conserved stress response pathway, the TGF-β pathway. Our goals are to 1) determine how C. elegans responds to potential therapeutic compounds, including nanocarriers and amidoximes (potential anti-cancer drugs), and 2) determine if the DBL-1 TGF-β pathway is required for a general stress response to toxic compounds. We first established whether potential drug delivery vehicles (three nanocarriers) and anti-cancer drugs (two amidoximes) show toxicity by determining the lethal concentration (LC50) on wild-type animals. Milder effects of these compounds on the organism were determined by assaying growth rate, body morphology, brood size, and aversion to the compounds. To determine the role of the DBL-1 TGF-β signaling pathway in the organismal response to abiotic stress, we are analyzing the effect of increased and decreased DBL-1 TGF-β pathway signaling on the animals’ response to these and other established toxic compounds.