menu top picHOME



                                                        Dr. George Bittner

George photo

 

Office: PAT 321

Lab: PAT 315

Phone: (512) 471-5454

Email: bittner@austin.utexas.edu

Mailing Address: 

The University of Texas at Austin 
Section of Neurobiolgy
1 University Station C0920
Austin,TX 78712-1095

George Bittner graduated from Duke University in 1962 where he received his AB in Chemistry, Magna Cum Laude. He entered Stanford University as an MD/Ph.D. student in 1962. He withdrew in good standing (6th in Class) from Stanford Medical School in 1966 to devote full time to research under the tutelage of Dr. Donald Kennedy (Chairman of Biological Sciences). He received his Ph.D. in Neuroscience in 1967 from Stanford University. He began his postdoctoral work in the Department of Anatomy and the Brain Research Institute at UCLA with Dr. Jose Segundo and joined the faculty at the University of Texas in 1969. Dr. Bittner has had extensive collaborations with scientists in the US. He has been a Visiting Professor at Case Western Reserve University in Cleveland and a visiting scholar at the University of Western Australia (Nedlands,Perth). He has served on many NIH and NSF panels and was Chairperson of the Neuroscience Panel for Howard Hughes and NSF Predoctoral Fellowships in1996. his research is widely known both nationally and internationally, as recognized in part by a Research Career Development Award from the National Institutes of Health, his election as a fellow of the American Association for the Advancement of Science (AAAS) in 1992. Dr. Bittner was one of four founding members of the Institute for Neuroscience at the University of Texas and served for over a decade on its Executive Committee. He is a Professor of Neurobiology and Pharmacology at the University of Texas at Austin and an adjunct Professor at the Department of Physiology/Biophysics at the University of Texas Medical Branch (UTMB) at Galveston, TX.

Research Interests

We currently examine how cellular/molecular mechanisms can produce or induce long term survival of the distal (anucleate) stump of severed axons and the eventual reconnection or regeneration of those axons. These cellular/molecular mechanisms include (A) mechanisms for rapid sealing of cell membranes, including cut axonal ends (B) induced rapid (within seconds) reconnection/fusion of the proximal and distal stumps of severed mammalian axons, (C) induced survival of anucleate mammalian axons, and (D) induced outgrowths from proximal stumps of severed axons.

To restore function, proximal stumps of severed mammalian axons connected to their cell bodies must first rapidly seal their cut ends and then eventually regenerate the severed distal (anucleate) segment which normally degenerates in 6-48 hours. Until recently, axonal regeneration in mammals was considered impossible in the central nervous system (CNS) or slow (1 mm/day) and unspecific in the peripheral nervous system (PNS).

(A) We have recently shown that plasmalemmal damage in axons and other eukaryotic cells is repaired by an accumulation of vesicles and other membranous structures which fuse or otherwise interact with each other and the plasmalemma to form a diffusion barrier. The membranous structures that seal plasmalewmmal damage can arise from preformed structures (predocked vesicles, transport vesicles, etc) or from Ca2+-induced structures ( endocytotic vesicles, SER budding, myelin delaminations,etc). We are currently examining the molecular mechanisms responsible for vesicle formation, movement, and fusion -- and how sealing of a damaged plasmalemma can be enhanced (e.g., by exogenous calpain) or retarded (e.g., by metabolic inhibitors, antibodies to VAMPS or SNARES,etc).

(B) We have recently shown that polyethylene glycol (PEG) solutions can, within seconds, rejoin the severed halves of mammalian spinal or sciatic axons whose cut ends are induced to remain open by hypotonic salines containing reduced Cao. Using this technique originally developed to repair giant invertebrate axons, we are now restoring behavioral function to rats with hemisected spinal cords or severed sciatic nerves. We have also developed PEG-based hydrogels to provide mechanical strength in vivo to PEG-fused axons in rat spinal cords or sciatic nerves. That is, PEG-fused axonal ends lack mechanical strength and often pull apart when the animal recovers from anesthesia and begins to move about. Hence, we have recently developed photo-crosslinkable PEG-based hydrogels which are biocompatible, adhere tightly to glia and connective tissue elements to provide mechanical strength to PEG-fused axons, and begin to reabsorb sixty days after application.

(C) We have developed techniques to greatly retard the rate of degeneration of severed distal axons to increase the time after injury that they can be PEG-fused. We have shown that anucleate myelinated axons will survive for at least 7 days in vivo if the axons are maintained at 15o C in a temperature-controlled cuff or if the animal is injected with cyclosporin A to inhibit the immune system. We are now examining other cellular.molecular mechanisms to retard axonal degeneration.

(D) We are developing procedures to induce or guide outgrowths from the proximal stumps of severed CNS axons in the spinal cord of rats. These techniques include fibrin-based growth guides, transplants of adult stem cells, and local application of neurotrophic factors by micro-pumps or genetically modified cells.