Grant: Discovery Grants Program - Individual

Nerve cells communicate with each other by releasing chemical signals that alter electrical activity in their target cells. Most of these chemical signals are ""peptides"" (short chains of amino acids), and some are ""biogenic amines"", smaller compounds derived from amino acids. The human brain contains over 100 different peptides, and much about their functions is still not understood. My lab examines how these signaling molecules function and how they give rise to behaviour. We use crayfish and fruit flies as model experimental systems because they contain fewer nerve cells than humans and most other animals, and many of the nerve cells can be identified easily from one specimen to another. The fruit fly genome is fully sequenced, providing an array of ""molecular tools"" that allow us to determine how specific genes and proteins allow peptides and biogenic amines to alter the activity of nerve and muscle cells. Crayfish have the advantage of larger size, providing more material for biochemical analysis. We use these two model systems to determine the mechanisms through which specific signaling molecules alter the electrical properties of neurons, contraction of muscles and, ultimately, behaviour. During the next five years we will focus mainly on two peptides (proctolin and DPKQDFMRFamide) that are found in fruit flies. Both peptides are neurohormones that induce contraction in muscles and increase the strength of contraction when the muscles are activated by the nerve cells supplying them (motor neurons). We will identify the chemical signaling pathways inside the muscle cells that underlie the effects of these peptides on contraction. In addition to its role as a neurohormone, one of these peptides (proctolin) is released directly onto muscle cells by motor neurons. We will study the consequences of this dual-role of proctolin and determine whether its release from nerve terminals can affect its ction as a circulating hormone. We will also examine the role of proctolin in crawling and turning behaviours exhibited by fruit fly larvae (maggots). We will determine whether proctolin acts within the central nervous system, on muscles or at both sites, and we will identify the cells on which proctolin acts. These studies will increase our understanding of how neuropeptides act on cells and, ultimately, how their actions affect behaviour. This work is important for understanding the fundamental mechanisms underlying behaviour. It is also important to understand how neuropeptides function because they are involved in several diseases.