Harold B. Dowse

Professor Emeritus of Biological Sciences, Cooperating Professor of Mathematics and Statistics

Research Topic:
Genetic and molecular analysis of cardiac pacemakers; biology of cellular oscillators; mathematical analysis and modeling of biological systems

Research Program:
I am a comparative physiologist with a background in mathematics and genetics.

Molecular Mechanisms in Cardiac Physiology
I am investigating cardiac function at the cellular level in Drosophila melanogaster using molecular, genetic, and pharmacological tools. The heart of this organism makes an ideal model for probing the way in which heartbeat is generated. We have discovered a number of mutations which render the heart arrhythmic, and probing the way in which these lesions affect the beat yields information on the ion channels constituting this electrochemical pacemaker. We use neurotransmitters and ion channel specific toxins to alter function. I have cloned a calcium channel central to the pacemaker and am expressing this channel in Xenopus oocytes to determine its characteristics. This three-pronged approach yields a clearer picture of the self-sustained oscillation driving the heart. Owing to homologies among ion channels in the mammalian and insect heart, we expect to shed light on the latter’s more complicated system with this model.

Digital Signal Analysis
In my work with circadian rhythms and heartbeat, I have adapted a number of digital signal analysis techniques for use with biological systems. One of these techniques is Maximum Entropy Spectral Analysis. More recently, I have adapted wavelet analysis techniques for use in circadian rhythms. I am currently investigating acoustic signals produced by male Drosophila during courtship. There is a great deal of species-specific information carried by these songs. I have adapted wavelet decomposition techniques for time-frequency of analysis of these signals as well. Wavelet analysis is a new method that holds promise for other biological signals, including heartbeat.

Circadian Rhythms
I continue my work on circadian and ultradian rhythms in collaboration with investigators at other institutions, principally Brandeis University. I am particularly interested in ultradian rhythms and their potential role underlying the 24-h oscillator, and have worked on the role of the cry gene in peripheral clocks and social interactions that can lead to resetting of the clock.

Selected Publications:

Beasley, V and H.B. Dowse. 2017 Suppression of Tryptophan 2,3-Dioxygenase Produces a Slow Heartbeat Phenotype in Drosophila melanogaster In Press

VanKirk T, Powers E, Dowse, HB. 2016. Melatonin increases the regularity of cardiac rhythmicity in the Drosophila heart in both wild-type and strains bearing pathogenic mutations. J Comp Physiol B doi:10.1007/s00360-016-1019-8

Vrailas-Mortimer Alysia, Sarah M. Ryan, Matt Avey, Harold Dowse and Subhabrata Sanyal. 2014. p38 MAP Kinase regulates circadian rhythms in Drosophila. J. Biol. Rhythms, 29: 411–426.

Vrailas-Mortimer, A., Gomez, R., Dowse, H, and Sanyal, S.  2012.  A survey of the protective effects of some commercially available antioxidant supplements in genetically and chemically induced models of oxidative stress in Drosophila melanogaster. Experimental Gerontology, 47:712-722.   Awarded Best Paper of the Year in the journal.

Dowse, H., J. Umemori, and T. Koide. 2010. Ultradian Components in the Locomotor Activity Rhythms of the Genetically Normal Mouse, Mus musculus. J. Exp. Biol., 213: 1788-1795.