.: Department of Biology: Mark Harlow

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Mark Harlow received dual B.S. degrees (1994) in Biochemistry and Genetics from Texas A&M University. He did his Neurosciences Ph.D. (2001) and postdoctoral work at Stanford University in the lab of U. Jack McMahan. He joined the Department of Biology at Texas A&M University in 2009.

Mark Harlow

Mark Harlow
Assistant Professor

3258 TAMU
College Station, TX 77843-3258

Office:
Interdisciplinary Life Sciences Building
Room 3126B
979-4585560

Lab:
Interdisciplinary Life Sciences Building
Room 3218
979-458-5563

Fax: 979-845-2891
Email: mharlow@mail.bio.tamu.edu

The Structural Organization of Macromolecules Responsible for Neurotransmitter Secretion During Synaptic Transmission

Direct observation of tissue specimens by high-resolution electron microscopy combined with advanced computational analysis provides a unique view of the molecular basis of cell function. The nerve synapse serves as a model system for one such cell function – timed release of signaling products. In the case of the vertebrate neuromuscular junction the product being released is the neurotransmitter acetylcholine, which at rest is stored in synaptic vesicles within the nerve terminal. Prior to fusing with the presynaptic plasma membrane for exocytosis of their neurotransmitter, synaptic vesicles become both docked on the presynaptic membrane and associated with its attached proteinaceous organelles, the active zone material.

The focus of my research over the next several years will concern the arrangement of proteins in synaptic vesicles as revealed by Electron Tomography. Specifically I will use Electron Tomography in combination with other techniques (i.e. cryo EM, high resolution light microscopy, fluorescent and EM labeled probes) to study the organized macromolecular filaments in the lumen of synaptic vesicles, which are thought to be composed of the luminal domains of proteins in the vesicle membrane, and the role they play in synaptic function. I propose five projects:

To characterize the structure of synaptic vesicle intraluminal filaments at high resolution.
To identify the macromolecules which constitute the synaptic vesicle intraluminal filaments.
To determine the fate of the synaptic vesicle luminal filaments during exocytosis of neurotransmitter.
To study the process by which the organization and arrangement of luminal filaments mature during synaptic vesicle recycling.
To examine the role of the luminal filaments in the function and formation of synaptic vesicles.

Nagwaney*, S., Harlow* M.L., Jung, J.H., Szule, J.A., Ress, D., Marshall, R.M., and U.J. McMahan (2009). Macromolecular connections of the active zone to docked synaptic vesicles and the presynaptic membrane at neuromuscular junctions of the mouse. (Accepted for publication – Journal of Comparative Neurology; * = first authorship shared equally)

Ress, D., Harlow, M.L., Marshall, R.M., and U.J. McMahan (2004). Methods for generating high-resolution structural models from electron microscope tomography data. Structure, 12:1763-74.

Ress, D., Harlow, M.L., Marshall , R.M. and U.J. McMahan (2003). Optimization method for isodensity surface models obtained with electron microscope tomography data. Engineering in Medicine and Biology Society, 2003. Proceedings of the 25th Annual Conference of the IEEE, 1:774-77.

Harlow, M.L., Ress, D., Stoschek, A., Marshall, R.M., and U.J. McMahan (2001). The architecture of active zone material at the frog's neuromuscular junction. Nature, 409:479-84.

Ress, D., Harlow, M., Schwarz, M., Marshall, R.M., and U.J. McMahan (1999). Automatic acquisition of fiducial markers and alignment of images in tilt series for electron tomography. J. Elect. Microsc., 48:277-87.

Harlow, M., Ress, D., Koster, A., Marshall, R., Schwarz, M., and U. McMahan (1998). Dissection of active zones at the neuromuscular junction by EM tomography. J. Physiol. (Paris), 92:75-78.

Hegerl, R., Stoschek, A., Yu, T.P.Y., and M. Harlow (1996). Denoising tomographic reconstructions of individual structures using wavelet decomposition. Proceedings of the 11th European Congress on Microscopy, Dublin.