Posts classified under: Synapses, Cells, and Circuits

Steve Cannon, M.D., Ph.D.

Biography

The primary research interests of our laboratory are how ion channels regulate the electrical excitability of cells and how defects in these channels lead to human disease. In the past two decades, mutations of ion channel genes have been found to be the primary cause for over 100 human diseases. Our research program is focused on the mechanistic basis for a group of inherited conditions that alter the electrical excitability of skeletal muscle, including periodic paralysis and myotonia. We have characterized the gating defects of mutant channels, generated computational models of muscle excitability, and produced genetically-engineered mice to gain insights on the pathomechanisms of these disorders and to explore therapeutic interventions.

Gordon Fain, Ph.D.

Biography

A vertebrate photoreceptor uses a G-protein receptor (rhodopsin) and a G-protein cascade to produce the electrical response that signals a change in light intensity. Powerful new techniques have made it possible to understand the working of this cascade in extraordinary detail. The reason for this is that practically every protein involved in the cascade in a photoreceptor, from the pigment molecule rhodopsin to the G-protein and channels, but including also a large number of control proteins, are expressed only in the photoreceptors and nowhere else in the body. This makes it possible with genetic techniques to create mice in which these proteins have been knocked out, over or under expressed, or replaced with proteins of modified structure. We use electrical recording to study the effects of such genetic alterations on the light responses of mouse rods and cones, in order to understand the role of these proteins in the visual cascade. We are especially interested in modulatory enzymes and their function in light and dark adaptation. We also have a long-standing interest in mechanisms of photoreceptor degeneration in genetically inherited disease.

Publications

A selected list of publications:

Fain Gordon, Sampath Alapakkam P   Rod and cone interactions in the retina F1000Research, 2018; 7: .
Morshedian Ala, Woodruff Michael L, Fain Gordon L   Role of recoverin in rod photoreceptor light adaptation The Journal of physiology, 2018; 596(8): 1513-1526.
Morshedian Ala, Toomey Matthew B, Pollock Gabriel E, Frederiksen Rikard, Enright Jennifer M, McCormick Stephen D, Cornwall M Carter, Fain Gordon L, Corbo Joseph C   Cambrian origin of the CYP27C1-mediated vitamin A Royal Society open science, 2017; 4(7): 170362.
Morshedian Ala, Fain Gordon L   Light adaptation and the evolution of vertebrate photoreceptors The Journal of physiology, 2017; 595(14): 4947-4960.
Kaylor Joanna J, Xu Tongzhou, Ingram Norianne T, Tsan Avian, Hakobyan Hayk, Fain Gordon L, Travis Gabriel H   Blue light regenerates functional visual pigments in mammals through a retinyl-phospholipid intermediate Nature communications, 2017; 8(1): 16.
Morshedian Ala, Fain Gordon L   The evolution of rod photoreceptors Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2017; 372(1717): 16.
Ingram Norianne T, Sampath Alapakkam P, Fain Gordon L   Why are rods more sensitive than cones? The Journal of physiology, 2016; 594(19): 5415-26.
Reingruber Jürgen, Holcman David, Fain Gordon L   How rods respond to single photons: Key adaptations of a G-protein cascade that enable vision at the physical limit of perception BioEssays : news and reviews in molecular, cellular and developmental biology, 2015; 37(11): 1243-52.
Morshedian Ala, Fain Gordon L   Single-photon sensitivity of lamprey rods with cone-like outer segments Current biology : CB, 2015; 25(4): 484-7.
Reingruber Jürgen, Pahlberg Johan, Woodruff Michael L, Sampath Alapakkam P, Fain Gordon L, Holcman David   Detection of single photons by toad and mouse rods Proceedings of the National Academy of Sciences of the United States of America, 2013; 110(48): 19378-83.
Chen Ching-Kang, Woodruff Michael L, Chen Frank S, Chen Yenlin, Cilluffo Marianne C, Tranchina Daniel, Fain Gordon L   Modulation of mouse rod response decay by rhodopsin kinase and recoverin The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012; 32(45): 15998-6006.
Chen Jeannie, Woodruff Michael L, Wang Tian, Concepcion Francis A, Tranchina Daniel, Fain Gordon L   Channel modulation and the mechanism of light adaptation in mouse rods The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010; 30(48): 16232-40.
Fain Gordon L, Hardie Roger, Laughlin Simon B   Phototransduction and the evolution of photoreceptors Current biology : CB, 2010; 20(3): R114-24.
Okawa Haruhisa, Sampath Alapakkam P, Laughlin Simon B, Fain Gordon L   ATP consumption by mammalian rod photoreceptors in darkness and in light Current biology : CB, 2008; 18(24): 1917-21.
Dizhoor Alexander M, Woodruff Michael L, Olshevskaya Elena V, Cilluffo Marianne C, Cornwall M Carter, Sieving Paul A, Fain Gordon L   Night blindness and the mechanism of constitutive signaling of mutant G90D rhodopsin The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008; 28(45): 11662-72.
Fain GL   Why photoreceptors die (and why they don’t), BioEssays, 2006; 28: 344-354.