Laboratory of Enrico Nasi and Maria Gomez
|Enrico Nasi, Adjunct Senior Scientist
Professor, Universidad Nacional, de Colombia
Cellular Dynamics Program
Cellular biophysics, Sensory physiology
|Address||MBL, 7 MBL Street, Woods Hole MA 02543|
For many years the research in our laboratory has focused on the mechanisms by which visual cells generate an electrical response to light, and adjust their sensitivity and kinetics for optimal performance in the face of widely changing conditions of ambient stimulation. More generally, we have maintained a long-standing interest in the problem of amplification and modulation of G-protein mediated signal transduction (of which the light response is a prime example), and the ionic channels that underlie the receptor potential. Two canonical classes of photoreceptor cells – microvillar and ciliary – are found in animals, with distinct structural, physiological and biochemical properties; these were long thought to be a prerogative of vertebrates and invertebrates, respectively, but recent developments indicate that both lineages are phylogenetically ubiquitous, and suggest a common evolutionary origin of light transduction. The signaling cascades involved (namely, phosphoinositoid- and cyclic nucleotides-based) are widespread in nature, and participate in processes as diverse as the activation of the immune response, fertilization, and chemoreception, so that the elucidation of photo-excitation schemes impacts areas beyond sensory biology. For our work, we have developed preparations of enzymatically isolated photoreceptors from the unique double retinas of some marine organisms as well as from the neural tube of the most basal chordate, amphioxus. Our studies rely heavily on patch-clamp recording, calcium imaging, immunodetection, and molecular biology to unravel the events that are triggered by the absorption of a photon and culminate in the regulation of ionic currents through membrane channels. Key questions concern the molecular identity of the signaling elements involved, and the modulatory mechanisms by which the gain and bandwidth of the transduction process are adjusted to optimize signal-to-noise ratio. In addition, we are exploring the implications of these issues for the evolutionary history of light detecting cells, their diversity and the mechanistic basis of their specialization to fulfill diverse roles (from the high temporal and spatial resolution needed for visually guided behavior, to the sheer discrimination of light and darkness to regulate circadian functions).
|Address||MBL, 7 MBL Street, Woods Hole MA 02543|
The main research interest in our laboratory centers on the mechanisms of G protein-mediated signaling, using isolated photoreceptor cells as a particularly convenient experimental model system: stimulation can be controlled temporally and spatially with great accuracy, and signaling molecules are plentiful to facilitate their identification. Many of these cells are capable of extraordinary feats, producing a measurable change in membrane current or voltage upon absorbing a single photon, or generating a full-fledged response within a few milliseconds of stimulus onset. Moreover, the receptor operating characteristics are modulated to optimize responsiveness under different conditions of illumination. Light transduction exemplifies two of the most ubiquitous messenger systems in nature, namely, phosphoinositides and cyclic nucleotides, which operate in the two well-known lineages of light-sensing cells (microvillar and ciliary). Recently, our interest has expanded to include cells that signal light for non-visual purposes, and use the novel photopigment melanopsin. In mammals, this photopigment is expressed by a small population of ganglion cells in the retina, which convey information about light and darkness to the biological clock in the hypothalamus. This information is crucial, among other things, for the regulation of the circadian rhythms and associated control of hormonal secretion. Because these cells are scarce and difficult to identify morphologically, we turned to the chordate amphioxus, where melanopsin expresses in two types of microvilli-bearing cells abundantly present along the neural tube. The advantages afforded by this organism allowed us to examine the melanopsin-dependent light-signaling cascade, showing that it parallels that of the photoreceptors of insects and mollusks. These light sensors, therefore, bridge the gap between the ‘rhabdomeric’ visual cells of invertebrates and the ‘circadian’ receptors of higher vertebrates, a linkage that had been traditionally dismissed. In addition, the unique position of amphioxus as the most basal living relative of vertebrates, the fact that is has remained virtually unchanged since its ancestral state, and the availability of its genome provide an unusually favorable window to examine the evolutionary history of circadian photoreceptors.