David A. Price
(Ph.D., Florida State University, 1977)

Associate Scientist and Molecular Lab Director, Whitney Laboratory

dprice@whitney.ufl.edu

Structure and Function of Neuropeptide Receptors

The main focus of our laboratory is on neuropeptides, which are important signaling molecules in the nervous systems of both humans and other animals. Our long-term goal is to understand how neuropeptides and their receptors are involved in the function of the nervous system. We use a comparative approach in which molecules involved in the control of basic physiological and behavioral processes in invertebrate animals are compared to similar molecules in humans. Such studies often provide insights that are missed in strictly medical studies.

A secondary focus of our work is on the commercial development of methods for the supersensitive detection of biological molecules. This work is conducted as an employee of BioTraces, Inc., a biotechnology-oriented company based in Herndon, Virginia.

Current Projects

We study neuropeptide receptors that act directly as ion channels. These receptors translate the neuropeptide message into a change in the ion currents flowing into the cell. Channels that are homologous to invertebrate neuropeptide receptors occur in humans where they are thought to be involved in pain perception. The responses of such mammalian channels to acidic stimuli are modulated by some of the same peptides that activate the invertebrate channels.

This year we continued our structure-activity studies on the acid sensing ion channels of mammals. Dr. Richard Doolin found the same peptides that are active on the molluscan channel also act on those of mammals. This study could lead to the design and development of peptides that may be beneficial in the treatment of pain resulting from acidic conditions.

We also study neuropeptide receptors that act by producing second messengers inside the cell when
the receptors are stimulated externally. These so-called G-protein-coupled receptors (GPCRs) are the most common type of receptors for neuropeptides.

We began studies on GPCRs for the neuropeptide FMRFamide by expressing known receptors from fruit fly in frog oocytes. This is a well-established method for studying the properties of ion channels, but it might not be the optimal system for our purposes. We are now beginning to express the ion channels in cultured cells. A possible FMRFamide receptor from oyster was cloned by Margaret Saunders, but firm evidence that this receptor actually responds to FMRFamide is still elusive.

Neuropeptide precursors are the focus of another project. Neuropeptides are produced in the nerve cells by the enzymatic breakage of large precursors at specific sites to generate many copies of the neuropeptide. Our interest is to determine which neuropeptides are redundant and which have unique activities.

We identified the gene for an unknown FMRFamide precursor in an on-line database. This gene was reported to be from a frog, which was confounding, since FMRFamide has never been found in vertebrates. However, on closer inspection we determined that it was actually derived from worms that the frog had eaten. We are continuing studies of the FMRFamide precursor in this segmented worm. We hypothesize that the segmented worm gene is very similar to the molluscan gene reflecting the common evolutionary history of these two groups.

As part of our work for BioTraces, we studied the protein makeup of Bacillus spores as a first step in designing methods that might influence the germination of anthrax (Bacillus anthracis) spores. Since germination of these spores is their first step in infecting people, inhibition of germination will prevent infection.

Personnel

David A. Price, Associate Scientist
Rebecca B. Price, Biological Scientist
Jocelyn Tulsian, Laboratory Assistant