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Séminaire - Graham Ellis-Davies“Light-directed neurobiology using two-photon microscopy”

Abstract :

Two-photon microscopy is useful for local photorelease of biological signals molecules such as glutamate and deep tissue imaging of synaptic structures in living mice. Recently several chemical biologists have attempted to photorelease two molecules using two wavelengths of light in a chromatically independent way. Such experiments typically show sequential not arbitrary photolysis of the two caged compounds. We have recently developed a new long wavelength caging chromophore, DEAC450, that allows arbitrary two-color photolysis in living cells. I show that DEAC450-caged neurotransmitters can be partnered with our previous developed short wavelength caged transmitters so as to fire and block neuronal action potentials with 2-color, 2-photon photolysis with single synapse precision. I will also present some of our recent work on in vivo longitudinal fluorescence imaging.

Selected publications

Crowe, S.E. and Ellis-Davies, G.C.R. (2014) Longitudinal in vivo two-photon fluorescence imaging. J. Com. Neuurol. 522, 1708-1727.

Watkins, S. Robel, S. Kimbrough, I.F., Robert, S.M., Ellis-Davies, G.C.R. and Sontheimer, H. (2014) Disruption of astrocyte-vascular coupling and the blood-brain barrier by invading glioma cells. Nature Commun. 5, e4196.

Crowe, S.E. and Ellis-Davies, G.C.R. (2014) Spine pruning in 5xFAD mice starts on basal dendrites of layer 5 pyramidal neurons. Brain Struct. Funct. 219, 571-580.

Amatrudo, J.M., Olson, J.P., Lur, G., Chiu, C.Q., Higley, M.J. and Ellis-Davies G.C.R. (2014) Wavelength-selective one- and two-photon uncaging of GABA. ACS Chem. Neurosci. 5, 64-70.

Olson, J.P., Banghart, M.R., Sabatini, B.L. and Ellis-Davies G.C.R. (2013) Spectral evolution of a photochemical protecting group for orthogonal two-color uncaging with visible light. J. Am. Chem. Soc. 135, 135, 15948-15954.

Scientific focus :

Biography

I spent several years as a postdoc in the Department of Physiology at the University of Pennsylvania. During that time my research changed from being purely focused on photochemistry to calcium regulated physiology. I started my own my own lab in 1995, and since then I have become interested in using photochemical methods to study neuronal plasticity and neuronal degeneration.

Research
New topic
Light has been used to study cells since their discovery at the end of the 17th century. The development of modern ultrafast lasers and transgenic fluorescent proteins provides the means to monitor (sub)cellular events in vivo. Such microscopy allows us to see into the brain at chosen intervals without disturbing it. Detection is so sensitive we can repeatedly pick out single synapses. Our approach is just like like taking daily (or weekly) photographs of a plant coming into bloom: time-lapse snap-shots enable you to construct a picture of the build up of a complex system step by step, in real time. We are currently applying this method to murine models of Alzheimer's disease, in order to study the causes and consequences of neurodegeneration during disease progression.

A second line of research is the use of light to control cell function. We use organic chemistry to construct photochemically labile molecules (caged compounds) that disgorge their contents upon illumination, so activating a selected biological target. We are privileged to collaborate with several labs around the world that use caged compounds to study cellular function, including Kamran Khodakhah (Einstein), Erst Niggli (Bern), Phil Haydon (Tufts), George Augustine (Duke), Haruo Kasai (Tokyo), Brain MacVicar (Vancouver), Ed Levitan (Pitt), and Dwight Bergles (Hopkins).