Christopher V. Gabel, Ph.D.
B.A. Princeton University
Ph.D. Harvard University
Our research program is focused on the development and application of femtosecond laser surgery and optical neurophysiology to the study of the nervous system of the nematode worm C. elegans. Using tightly focused pulses from an ultrafast laser, we can ablate regions of biological tissue with submicron precision, making it possible to snip individual nerve fibers within an intact worm (Fig 1). This enables in vivo study of neural regeneration and dissection of neurocircuitry at a new level of resolution. A small transparent body, simple stereotyped nervous system and powerful genetic tools combined to make C. elegans an ideal model organism for this work. Femtosecond laser technology applied to this versatile and tractable system allows us to tackle fundamental questions in neural regeneration and function.
Calcium imaging in regeneration
One aim of the lab is to elucidate the spatiotemporal calcium dynamics and signaling that accompany neural damage and regeneration in vivo. By combining in vivo calcium imaging with femtosecond laser surgery in C. elegans, we have recently measured large calcium transients in the targeted neuron following laser damage. Sub-cellular measurements along a single axon, reveal calcium waves that initiate at the cut point and propagate along the axon to the cell soma. Calcium measurements are made using the genetically encoded fluorescence calcium indicator, cameleon, expressed in selected target neurons within intact animals. Our analysis of calcium regulatory mutations using this technique will help identify the genetic and molecular mechanisms that enable neurons to recognize and respond to injury.
High-throughput genetic screening and time-lapse imaging
Microfluidic devices and techniques are emerging as a powerful tool for manipulating and observing C. elegans. Working with members of the Whitesides lab at Harvard University we are developing techniques for parallel processing of up to one hundred worms at a time. Specially designed micron-scale channels physically restrain individual worms for laser surgery, and house them for up to 24 hours to enable quantitative re-imaging during regeneration. Such devices dramatically improve experimental throughput, eliminate the need for pharmacological anesthetics, and allow for large-scale genetic screening. They also facilitate detailed time-lapse imaging, allowing for a systematic study of growth cone formation and dynamics during regeneration. This is providing a new level of resolution with which to characterize genetic mutations and better understand the regenerative process. We will use this technology to investigate fundamental questions about neural regeneration, such as the effect of aging, the role of cell death pathways, and the differentiation during development that dictates the regenerative abilities of specific neuron types.
Simple circuit analysis
The simplicity of the C. elegans nervous system facilitates the comprehensive, quantitative analysis of its behavioral neural circuitry. We are combining the surgical precision of femtosecond laser surgery with quantitative behavioral analysis and optical neurophysiology to study the operation of C. elegans neural circuits. C. elegans circuits regulating a wide range of behaviors, from simple motility coordination to complex navigational strategies have been studied, but the computational properties of these circuits remain poorly understood. Sub-cellular ablations, snipping specific nerve fibers and/or removing individual neural synapses, made possible with femtosecond laser surgery, will bring this analysis to a new level.
Hulme S. E., Gabel C. V. and Shevkoplyas S. S., “A Microfluidic Tool for Immobilizing C. elegans”, in “Microdevices in Biology & Medicine”, Nahmias Y. and Bhatia S. N., eds., Artech House, Boston, 2009
Gabel C. V., “Femtosecond Lasers in Biology: Nanoscale Surgery with Ultrafast Optics”, review article, Contemporary Physics, 49(6): 391-411, 2008
Luo L., Gabel C. V., Ha H., Zhang Y., and Samuel A. D. T., “Olfactory Behavior of Swimming C. elegans Analyzed by Measuring Motile Responses to Temporal Variations of Odorants”, J Neurophysiol, 99: 2617-2625, 2008
Gabel C. V., Antoine F., Chuang C., Samuel A. D. T., Chang C., “Distinct Cellular and Molecular Mechanisms Mediate Initial Axon Development and Adult-Stage Axon Regeneration in C. elegans”, Development, 135: 1129-1136, 2008
Chi C. A., Clark D. A., Lee S., Biron D., Gabel C. V., Brown J., Sengupta P., Samuel A. D. T., “Temperature and Food Mediate Long-Term Thermotactic Behavioral Plasticity in C. elegans by Association-Independent Mechanisms”, JexpBiol. 210: 4053-4052, 2007
Gabel C. V., Gabel H., Pavlichin D., Kao A., Clark D. A., Samuel A. D. T.. “Neural Circuits Mediate Electrosensory Behavior in Caenorhabditis elegans”, J. Neuroscience 27(28): 7586-7596, 2007
Korta J., Clark D. A., Gabel C. V., Mahadevan L., Samuel A. D. T., “Mechanosensation and Mechanical Load Modulate the Locomotory Gait of Swimming C. elegans”, JEB 210: 2383-2389, 2007
Clark D. A., Gabel C. V., Gabel H., Samuel A. D. T., “Temporal Activity Patterns in Thermosensory Neurons of Freely Moving C. elegans Encode Spatial Thermal Gradients”, J. Neuroscience 27(23): 6083-6090, 2007
Clark D.A.*, Gabel C. V.*, Lee T. M., Samuel A., “Short-term Adaptation and Temporal Processing in the Cryophilic Response of Caenorhabditis elegans”. J Neurophysiol. 97(3): 1903-1910, 2007 (* co-first authors)
Biron D., Shibuya M., Gabel C., M. Wasserman S. M., Clark D. A., Brown A., Sengupta P., and Samuel A. D. T., “A Diacylglycerol Kinase Modulates Long-Term Thermotactic Behavioral Plasticity in C. elegans”, Nature Neuro, 9(12): 1499-1505, 2006
Chung S. H., Clark D. A., Gabel C. V., Mazur E., Samuel A. D. T., “The Role of the AFD Neuron in C. elegans Thermotaxis Analysed Using Femotsecond Laser Ablation”, BMC Neuroscience, 7:30, 2006
Colosimo M. E., Brown A., Mukhopadhyay S., Gabel C., Lanjuin A. E., Samuel A. D. T., Sengupta P., “Identification of Thermosensory and Olfactory Neuron-specific Genes via Expression Profiling of Single Neuron Types”, Curr.Bio., 14(24): 2245-2251, 2004
Gabel C. V. & Berg H. C., “The Speed of the Flagellar Motor of Escherichia coli Varies Linearly with Protonmotive Force”. Proc. Natl. Acad. Sci. USA, 100: 8748-8751, 2003
Gifford S. C., Frank, M. G., Dergan J., Gabel C., Austin R. H., Yoshida T., Bitensky M. W., “Parallel Micro-channel Based Measurement of Individual Ethrocyte Areas and Volumes”. Biophys. J. 84(1): 623-633, 2003
Carlson R. H., Gabel C. V., Chan S. S., Austin R. H., Brody J. P., Winkelman J.W., “Self-sorting of White Blood Cells in a Lattice”, Phys Rev Lett, 79: 2149-2152, 1997
Department of Physiology and Biophysics
Boston University School of Medicine
700 Albany Street
Boston MA 02118-2526
Fax: (617) 638-4273