Michael J. O’Donnell, Ph.D.
Cellular mechanisms of epithelial ion transport. Control of ion transport by peptides and intracellular second messengers.
Membrane Physiology of Ion transport and Excretion
The primary goal of my research program is to elucidate the cellular and molecular mechanisms of excretion and ion transport, particularly by insect epithelia. We study how such processes are controlled by hormones and intracellular second messengers, and how mechanisms for excretion and ion transport are altered in response to changing environmental conditions. Blood feeding insects such as mosquitoes are of enormous importance as vectors of diseases such as malaria, and our studies of physiological mechanisms of ionoregulation and excretion provide insights that we hope will aid development of novel, environmentally-benign insecticides for pest species. Recently we have become fascinated by the ability of insects to rid themselves of toxins. Co-evolution of insects with flowering plants means that many insects are extraordinarily effective at detoxifying synthetic or natural pesticides, and the excretory system plays an important role in elimination of toxins or their metabolites.
My research makes extensive use of electrophysiological methods, including intracellular recording, ion-selective microelectrodes and patch clamping. My students and I develop or adapt specialized micro-techniques for measuring pH or ion concentrations inside or adjacent to epithelial cells, or in nanoliter samples of biological fluids. We have recently developed a method of measuring transport of fluorescent substrates of ion transporters by means of confocal laser scanning microscopy of nanoliter droplets of secreted fluids, and we have used this technique to assess the roles of transporters related to p-glycoproteins and multidrug resistant proteins (MRP) in insect Malpighian (renal) tubules. We are also one of the few labs in Canada to make use of the Automated Scanning Electrode Technique (ASET). Transport of ions into or out of cells perturbs the concentration of ions in the unstirred layer (USL) near the surface of the cell. ASET uses computer-controlled stepper motors to position ion-selective microelectrodes near cells and measure tiny changes ( <0.04% ) in ion concentration between two positions within the USL. The difference in ion concentration is then used to calculate the rate of ion transport using the Fick equation