Regulation of Chemoreceptor Gene Expression in C. elegans

Brandeis University, Waltham MA

Investigators

Abstract

Animals must alter their development and behavior in response to ever-changing environmental conditions. These adaptive changes are ultimately mediated via changes in gene expression patterns. However, the mechanisms by which environmental cues are translated into the appropriate changes in gene expression are not fully understood. The goal of this proposal is to investigate the molecular pathways by which the expression of chemosensory receptor genes is regulated by environmental signals in the model organism C. elegans. C. elegans responds to chemicals in its environment via chemosensory receptor proteins expressed in a small number of chemosensory neurons. It has previously been shown that worms alter their chemosensory behaviors under different environmental conditions, and that the expression of chemosensory receptor genes is modulated by external cues. These data have led to the hypothesis that environment-mediated behavioral changes may in part, be mediated via changes in chemosensory receptor gene expression. In the previous funding period, a signaling pathway comprised of the KIN-29 kinase, the MEF-2 transcription factor, and the HDA-4 histone deacetylase proteins were shown to regulate the expression of a subset of chemosensory receptor genes in a manner that may be dependent on levels of chemosensory neuron activity, which in turn may be regulated by external signals. The specific aims of this proposal are to: AIM 1. Explore neuronal activity-mediated regulation of chemosensory receptor gene expression by KIN-29. The goal of this aim is to explore how electrical activity of the neuron plays a role in regulating KIN-29-mediated gene expression. The mechanisms of KIN-29 function will be investigated using biochemical methods. AIM 2. Analysis of additional genes acting in the KIN-29-regulated pathway for CR gene expression. The goal of this aim is to exploit the genetic power of C. elegans to identify additional components of the KIN-29-regulated pathway. Since molecules related to KIN-29, MEF-2 and HDA-4 have been shown to act in similar processes in vertebrates, it is expected that principles derived from the proposed experiments will be generally applicable in other systems. Brandeis University is a private liberal arts University with a large undergraduate population. Biology is the most popular major, and the Department is committed to providing all interested undergraduates with strong scientific training of which participation in research is a vital component. Three undergraduates were involved with this project in the past funding period and were included as co-authors on publications. It is a goal of this work to train graduate and undergraduate students in the scientific research method. Training and knowledge provided by this work will enable them to be effective in their future careers of choice, and to effectively communicate scientific information to the public.