91��������

91�������לWhat91�������יs that?91�������ם a student in the MBL Neurobiology course asked Tom Reese of the National Institutes of Health last week, as they looked at a black-and-white image of brain structure with an electron microscope. 91�������לIt91�������יs a blood vessel,91�������ם Reese said, and then guided him to see the junctions between its specialized endothelial cells.

91�������לThat91�������יs the blood-brain barrier. We discovered how it works,91�������ם Reese explained to the undoubtedly startled student.

. In fact, Reese has been in the thick of several major scientific discoveries over the course of his career, although he is exceedingly humble (and humorous) about it.

91�������לI91�������יm the Forrest Gump of neurobiology!91�������ם he says, referring to the movie starring Tom Hanks. 91�������לGump is always there by chance when very important things happen91�������הhe91�������יs there when Kennedy solves the Cuban missile crisis91�������הbut he doesn91�������יt have a clue what91�������יs really going on. That91�������יs the way I feel! Life goes racing on in another direction, but Gump is always there for the big one.91�������ם

Since a career like Reese91�������יs seems unlikely to happen by chance, and because he has been a bedrock leader, mentor, and teacher in the MBL Neurobiology course for the past 40 years, a special symposium in Reese91�������יs honor will be held this Saturday, July 18, in MBL91�������יs Lillie Auditorium.

91�������לThe Thomas Sargeant Reese Symposium: Forty Years of Structural Neuroscience at MBL91�������ם was organized by JoAnn Buchanan of Stanford University/Allen Brain Institute, who has taught electron microscopy (EM) in the course for 20 years, along with a committee of present and former Neurobiology course directors. The Grass Foundation has provided generous support.

91�������לTom is a fabulous teacher. He is really, really into the fine structure of the nervous system, and he has made a lot of wonderful breakthroughs. You just want to sit with him at the electron microscope and listen to him. And that is what he still does with the students,91�������ם Buchanan says.

91�������לOne of the most amazing qualities about Tom is how highly creative he has been throughout his career,91�������ם says William (Bill) Green of the University of Chicago, a longtime colleague of Reese91�������יs and MBL Whitman Center Investigator. 91�������לTom91�������יs creativity is evident in the way he designs experiments and develops new techniques in order to approach scientific questions from new perspectives,91�������ם he says.

Reese became exceptionally well-integrated into the Neurobiology course when he ran a year-round laboratory at the MBL from 1980 to 1988, while maintaining his appointment at NIH (where he is currently Chief of the Laboratory of Neurobiology and Head of the Section on Structural Biology at the National Institute of Neurological Disorders and Stroke).

91�������לTom had this incredible facility in the basement of Loeb Laboratory with all his fancy EM equipment, and the Neurobiology course got to use his space all summer,91�������ם Buchanan says. Reese91�������יs MBL lab, a smaller version of which he still runs each summer, has hosted innumerable student projects, course training modules, and conversations about brain structure that can go on well into the night. It is an open-door place, as have been all of Reese91�������יs labs, and he believes that is what has enabled his many scientific and educational successes.

91�������לReally, what I have done is I have approached structural biology with a love and openness and really caring about it in such a way that I was able to welcome anyone who came along into my lab. We invite anybody in. We try to find something they know how to do and get them doing their best,91�������ם Reese says.

The collaborative path to major discoveries

Several scientists who at some point found themselves in Reese91�������יs lab91�������הand ended up making significant and even pioneering discoveries91�������הwill be presenting at this weekend91�������יs symposium.

Synapse on dendritic spine (EM). Credit: Thomas S. Reese

They include John Heuser, who came into Reese91�������יs lab at NIH as a postdoctoral fellow in the late 1970s. Reese and Heuser perfected an ingenious EM preparative technique, called freeze fracture, that allowed them to image fleeting events in neuronal communication that had never been captured before. , they made a major, fundamental contribution with their 91�������לfreeze-slammer91�������ם: They showed how neurons release their neurotransmitter-containing vesicles to be recycled for reuse, a theory they had proposed in 1973.

91�������לThat is my favorite experiment of all time,91�������ם says Erik Jorgensen, an MBL Whitman Center Investigator and Howard Hughes Medical Institute (HHMI) Investigator at University of Utah. Jorgensen, who has further developed the Reese-Heuser freezing technology at MBL, will also speak at the symposium.

And Ron Vale, whom Reese invited into his MBL lab in the summer of 1983, while Vale was an MD-PhD student at Stanford University in search of squid at MBL. That led to an incredibly successful collaboration with several other contributors at MBL, and the historic , the motor protein, in squid axoplasm.

91�������לIt was a perfect team, as we all brought different skills and thinking and enjoyed the camaraderie of working together on the problem,91�������ם wrote Vale, referring to Reese, Bruce Schnapp in Reese91�������יs lab, Michael Sheetz of Stanford, and himself.

91�������לA memorable highlight was Bruce and Tom combining video microscopy and EM to demonstrate that single microtubules support bidirectional organelle transport,91�������ם Vale says. 91�������לThis was one of the most challenging and elegant experiments that I have ever witnessed.91�������ם

In 2012, the Albert Lasker Basic Medical Research Award was given to Vale, Sheetz, and James Spudich of Stanford for their discoveries related to kinesin and other cytoskeletal motor proteins. Vale is now an MBL Whitman Center Investigator and an HHMI Investigator at University of California-San Francisco.

91�������לWe were lucky with that project,91�������ם says Reese of the kinesin discovery. 91�������לWe were lucky to have Bruce Schnapp, who really understood light microscopy; lucky to have Bruce and I to do the EM and show how the biochemistry fit together with the structure; lucky to have Vale, who is a brilliant experimentalist; and lucky to have Mike Sheetz91�������הVale benefited a lot from his interactions with Sheetz and Spudich.91�������ם

These are just at the tip of Reese91�������יs important collaborative discoveries, which have been published in nearly 200 scientific papers. The symposium this weekend will highlight Reese91�������יs extraordinary range and contributions to structural neuroscience over more than 50 years.

Still exploring

Today, Reese isn91�������יt done asking questions and seeking answers. On the contrary, he has recently developed a passionate interest in the evolution of the nervous system. He and his wife, Carolyn Smith, are studying this in Trichoplax, a tiny organism situated near the earliest metazoans (animals) in the Tree of Life.

91�������לI91�������יm totally a basket case about evolution now,91�������ם Reese says. 91�������לOur basic idea is that the control of digestion of this very simple, bottom-dwelling organism is the origin of the synapse.91�������ם He and Smith are still working out this hypothesis; they published a  and have a new one coming out this year.

91�������לOne of the high points of my life is Carolyn and I were invited to talk about Trichoplax at the Smithsonian Institution with all the hard-rock evolutionary people,91�������ם Reese says. 91�������לI was so excited! I felt like a teenager!91�������ם His face lights up, and it91�������יs easy to see why Reese has gathered around him such an extraordinary company of scientists to call colleagues.

###

The Thomas S. Reese Symposium is free and open to the public.

###

Selected References

Rall, W., Shepherd, G., Reese, T.S. and Brightman, M.W. "Dendrodendritic synaptic pathway for inhibition in the olfactory bulb." Exp. Neurol., 14: 44-56, 1966.

Reese, T.S. and Karnovsky, M.J. 91�������לJ. Cell Biol. 34: 207-217, 1967.

Brightman, M.W. and Reese, T.S. 91�������ל.91�������ם J. Cell Biol. 40: 648-678, 1969.

Heuser, J.W. and Reese, T.S. 91�������ל.91�������ם J. Cell Biol, 57: 315-344, 1973.

Brightman, M.W., Hori, M., Rapoport, S.I., Reese, T.S. and Westergaard, E. 91�������לOsmotic opening of tight junctions in cerebral endothelium.91�������ם J. Comp. Neurol, 152: 317-326, 1973.

Landis, D.M.D., Reese, T.S. and Raviola, E. "Differences in membrane structure between excitatory and inhibitory components of the reciprocal synapse in the olfactory bulb." J. Comp. Neurol, 155: 67-92, 1974.

Landis, D.M.D. and Reese, T.S. "Differences in membrane structure between excitatory and inhibitory synapses in the cerebellar cortex." J. Comp. Neurol, 155: 933-1026, 1974.

Henkart, M., Landis, D.M.D. and Reese, T.S. "Similarity of junctions between plasma membranes and endoplasmic reticulum in muscle and neurons." J. Cell. Biol, 70: 338-347, 1976.

Gulley, R.L. and Reese, T.S. "Intercellular junctions in the reticular lamina of the organ and Corti." J. Neurocytol, 5: 479-507, 1976.

Gulley, R.S. and Reese, T.S. "Freeze-fracture studies of the non-junctional membrane specializations in the organ of Corti." Anat. Rec., 189:109-124, 1977.

Gulley, R.L., Landis, D.M.D. and Reese, T.S. "Internal organization of membranes at end bulbs of Held in the anteroventral cochlear nucleus." J. Comp. Neurol., 180:707-742, 1978.

Henkart, M.P., Reese, T.S. and Brinley, Jr., F.J. "Endoplasmic reticulum sequesters calcium in the squid giant axon." Science, 202:1300-1303, 1978.

Heuser, J.E., Reese, T.S., Dennis, M.J., Jan, Y., Jan, L. and Evans, L.  J. Cell Biol., 81:275-300, 1979.

Ornberg, R.L. and Reese T.S. 91�������לBeginning of exocytosis captured by rapid-freezing of Limulus amebocytes.91�������ם J. Cell Biol., Jul;90(1):40-54, 1981.

Smith, J.E. and Reese, T.S. "Use of aldehyde fixatives to determine the rate of synaptic transmitter release." J. Exp. Biol., 89:19-29, 1980.

Heuser, J.E. and Reese, T.S. "Structural changes after transmitter release at the frog neuromuscular junction." J. Cell Biol., 88:564-580, 1981.

Pumplin, D.W., Reese, T.S. and Llinas, R. "Are the presynaptic membrane particles the calcium channels?" Proc. Nat'l. Acad. Sci. USA, 78:7210-7214, 1981.

Kachar, B. and Reese, T.S. "Evidence for the lipidic nature of tight junction strands." Nature, 296:464-466 (and cover), 1982

Schnapp, B.J. and Reese, T.S. "Cytoplasmic structure in rapid-frozen axons." J. Cell Biol., 94:667-669, 1982.

Dickinson-Nelson, A. and Reese, T.S. "Structural changes during transmitter release at synapses in the frog sympathetic ganglion. J. Neurosci., 3:42-52, 1983.

Landis, D.M.M. and Reese, T.S. "Cytoplasmic organization in cerebellar dendritic spines." J. Cell Biol., 97:1169-1178, 1983.

Bridgman, P.C. and Reese, T.S. "The structure of cytoplasm in directly frozen cultured cells: I. Filamentous meshworks and the cytoplasm ground substance." J. Cell Biol. 99:1655-1668, 1984.

Walrond, J.P. and Reese, T.S. "Structure of axon terminals and active zones at synapses on lizard twitch and tonic muscle fibers." J. Neurosci., 5:1118-1131, 1985.

Vale, R.D., Schnapp, B.J., Reese, T.S. and Sheetz, M.P. " Cell, 40:449-454, 1985.

Schnapp, B.J., Vale, R.D., Sheetz, M.P. and Reese, T.S. Cell, 40:455-462, 1985.

Vale, R.D., Schnapp, B.J., Reese, T.S. and Sheetz, M.P. n." Cell, 40:559-569, 1985.

Vale, R.D., Reese, T.S. and Sheetz, M.P.  Cell, 42:39-50, 1985.

Vale, R.D., Mitchison, T.J., Schnapp, B.J., Sheetz, M.R., Steuer, E. and Reese, T.S.  Cell, 43:623-632, 1985.

Bridgman, P.C., Kachar, B. and Reese, T.S. "The structure of cytoplasm in directly frozen cultured cells: II. Cytoplasmic domains associated with organelle movements." J. Cell Biol., 102:1510-1521, 1986.

Andrews, S.B., Leapman, R.D., Landis, D.M.D. and Reese, T.S. "Elemental distribution in pre-synaptic nerve terminals in the cerebellar cortex." Proc. Natl. Acad. Sci. USA, 84: 1713-1717, 1987.

Landis, D.M.D., Weinstein, L.A., Reese, T.S. "Substructure in the postsynaptic density purkinje cell dendritic spines revealed by rapid-freezing and etching." Synapse, 1:552-558, 1987.

Landis, D.M.D., Hall, A., Weinstein, L.A. and Reese, T.S. "The organization of presynaptic cytoplasm at the active zone of central nervous system synapses." Neuron, 1:201-209, 1988.

Khan, S., Dapice, M. and Reese, T.S. "Effects of mot gene expression on the structure of the flagellar motor." J. Mol Biol., 202:575-584, 1988.

Schnapp, B.J. and Reese, T.S. "Dynein is the motor for retrograde axonal transport of organelles." Proc. Nat. Acad. Sci., 86:1548-1552, 1989.

Tatsuoka, H. and Reese, T.S. "New Structural features of synapses in the anteroventral cochlear nucleus prepared by direct freezing and freeze-substitution. J. Comp. Neurol. 290: 343-357, 1989.

Khan, S., Humayun, I., and Reese, T.S. "New structural features of the flagellar base in Salmonella typhimurium revealed by rapid-freeze electron microscopy.91�������ם J. Bacteriology, 173(9):2888-2896, 1991.

Terasaki, M., Reese, T.S. "Characterization of endoplasmic reticulum by colocalization of BiP and dicarbocyanine dyes." J. Cell Science, 101:315-22, 1992.

Andrews, S.B., Gallant, P.E., Leapman, R.D., Schnapp, B.J., Reese, T.S. "Single kinesin molecules crossbridge microtubules in vitro." Proc. Natl. Acad. Sci. USA, 90:6503-6507,1993.

Bearer, E.L., DeGiorgis, J.A., Bodner, R.A., Kao, A.W., Reese, T.S. "Evidence for myosin motors of organelles in squid axoplasm." Proc. Natl. Acad. Sci. USA, 90:11252-11256, 1993.

Terasaki, M., Slater N.T., Fein, A., Schmidek, A., Reese, T.S. "Continuous network of endoplasmic reticulum in cerebellar Purkinje neurons." Proc. Natl. Acad. Sci. USA, 91:7510-7514, 1994.

Terasaki, M., Schmidek, A., Galbraith, J.A., Gallant, P.E., and Reese, T.S. "Transport of cytoskeletal elements in the squid giant axon." Proc. Natl. Aca. Sci. USA 92:11500-11503, 1995.

Zhao, R., Pathak, N., Jaffe, H., Reese, T.S. and Khan S. 91�������לFliN is a major structural protein of the C-ring in the Salmonella typhimurium flagellar basal body." J. Mol Biol., 261:195-208, 1996.

Muresan, V., Godek, C.P., Reese, T.S., and Schnapp, B.J. "Plus-end motors override minus-end motors during transport of squid axon vesicles on microtubules." J Cell Biol., 135(2): 383-397, 1996.

Leapman, R.D., Gallant, P.E., Reese, T.S. and Andrews, S.B. 91�������לPhosphorylation and subunit organization of axonal neurofilaments determined by scanning transmission electron microscopy.91�������ם Proc. Natl. Acad. Sci. USA, 94:529-539, 1997.

Pozzo-Miller LD, Pivovarova NB, Leapman RD, Buchanan RA, Reese T.S., and Andrews, SB. 91�������לActivity-dependent calcium sequestration in dendrites of hippocampal neurons in brain slices.91�������ם J Neurosci 17(22):8729-38, 1997.

Galbraith, J. A., Reese, T.S., Schlief, M.L. and Gallant, P.E. 91�������לSlow transport of unpolymerized tubulin and polymerized neurofilament in the squid giant axon.91�������ם Proc. Natl. Acad. Sci. USA 96:11589, 1999.

Dosemeci A, Reese TS, Petersen J, Tao-Cheng JH. 91�������לA novel particulate form of Ca(2+)/calmodulin-dependent protein kinase II in neurons.91�������ם J Neurosci. 2000 May 1;20(9):3076-84.

Dosemeci A, Tao-Cheng JH, Vinade L, Winters CA, Pozzo-Miller L, Reese TS. 91�������לGlutamate-induced transient modification of the postsynaptic density.91�������ם Proc. Natl. Acad. Sci. USA 2001 Aug 28; 98(18): 10428-10432.

DeGiorgis JA, Reese TS, Bearer EL. 91�������לAssociation of a nonmuscle myosin II with axoplasmic organelles.91�������ם Mol Biol Cell. 2002 Mar;13(3):1046-57.

Petersen JD, Chen X, Vinade L, Dosemeci A, Lisman JE, Reese TS. 91�������לDistribution of postsynaptic density (PSD)-95 and Ca2+/calmodulin-dependent protein kinase II at the PSD.91�������ם J Neurosci. 2003 Dec 3;23(35):11270-8.

Otmakhov N, Tao-Cheng JH, Carpenter S, Asrican B, Dosemeci A, Reese TS, Lisman J. 91�������לPersistent accumulation of calcium/calmodulin-dependent protein kinase II in dendritic spines after induction of NMDA receptor-dependent chemical long-term potentiation.91�������ם J Neurosci. 2004 Oct 20;24(42):9324-31.

Chen X, Vinade L, Leapman RD, Petersen JD, Nakagawa T, Phillips TM, Sheng M, Reese TS. 91�������לMass of the postsynaptic density and enumeration of three key molecules.91�������ם Proc. Natl. Acad. Sci. USA, 2005 Aug 9;102(32):11551-6.

Chen X, Winters C, Azzam R, Li X, Galbraith JA, Leapman RD, Reese TS. 91�������לOrganization of the core structure of the postsynaptic density.91�������ם Proc. Natl. Acad. Sci. USA 2008 Mar 18;105(11):4453-8.

Tao-Cheng JH, Crocker V, Winters CA, Azzam R, Chludzinski J, Reese TS. 91�������לTrafficking of AMPA receptors at plasma membranes of hippocampal neurons.91�������ם J Neurosci. 2011 Mar 30;31(13):4834-43.

Chen X, Nelson CD, Li X, Winters CA, Azzam R, Sousa AA, Leapman RD, Gainer H, Sheng M, Reese TS. 91�������לPSD-95 is required to sustain the molecular organization of the postsynaptic density.91�������ם J Neurosci. 2011 Apr 27;31(17):6329-38.

Linsalata A, Chen X, Winters C, Reese TS. 91�������לElectron tomography on γ-aminobutyric acid-ergic synapses reveals a discontinuous postsynaptic network of filaments.91�������ם J Comp Neurol. 2014 Mar;522(4):921-36.

Smith CL, Varoqueaux F, Kittelmann M, Azzam R, Cooper B, Winters CA, Eitel M, Fasshauer D, Reese TS. 91�������לCurrent Biol. 2014 Jul 21;24(14):1565-72.