Christopher V. Gabel, Ph.D.

Lab Website

Research

Neurophotonics in Simple Systems

Put simply, the Gabel Lab employs light to study neuroscience in worms. C. elegans, a microscopic nematode, or roundworm, exhibits characteristics that make it ideal for photonic interrogation of the nervous system. The microscopic animal is completely transparent, possesses the simplest of nervous systems and is genetically tractable with a vast library of well-defined mutants and straightforward expression of genetically encoded fluorophores in select neuron types. The C. elegans nervous system consists of 302 stereotyped neurons whose anatomy and connectivity is completely mapped. To this system the Gabel lab brings expertise in high-resolution laser ablation and fluorescence microscopy to study neuronal damage, regeneration and function.

Laser surgery and regeneration of single neurons

Employing a pulsed infrared laser, the Gabel lab performs subcellular ablations within bulk biological tissue. The super-high intensity of a tightly focused femto-second pulsed laser beam results in multi-photon absorption and vaporization of the tissue within the focal volume. At the same time, the low total energy of each light pulse minimizes collateral damaged to the surrounding tissue and minimal linear absorption of the infrared light enables deep beam penetration. Applied to C. elegans this technique enables selective severing of individual nerve fibers within intact adult animals.

Neurological damage presents a major medical challenge, as severed neurons within the mammalian central nervous system typically do not regenerate resulting in permanent and debilitating paralysis. Laser surgery in C. elegans allows in vivo study of neuronal damage and regeneration in a simple highly tractable and reproducible system. The animal’s simple, completely mapped, nervous system allows identification, targeting and severing of a particular neuron at a specific location. Subsequent time-lapse imaging quantifies the degree of regeneration that can be compared across genetic backgrounds, pharmacological treatments and experimental conditions. Armed with these tools the Gabel lab has performed a series of studies decoding the cell intrinsic mechanisms of neuronal damage, recovery and regeneration. Their studies have defined the role of apoptotic caspases (nominally known for mediating programed cell death during development) in regeneration (Pinan-Lucarre et al. PLoS Biology 2012). As a post-doc in the lab, Dr. Samual Chung, (currently an Assistant Professor of Bioengineering at Northeastern University) spear headed a study defining the effects of neuronal activity on regeneration (Chung et al. PNAS 2016). More recently, in a project initiated by Dr. Dan Taub, a former graduate student in the lab, the group has focused on the fundamental importance of cellular metabolism in dictating a neurons regenerative capacity. Notably, they have discovered post-translational protein modifications that can alter cellular metabolism to greatly enhance neuronal regeneration (Taub et al. Cell Reports 2018).

Neuronal imaging from single cell physiology to whole brain function

Calcium is a key second messenger modulating a wide range of cellular processes in neurons from synaptic release, to gene expression, to axon guidance. Genetically encoded fluorophores allow in vivo imaging of calcium dynamics on the cellular and subcellular scale. The Gabel lab has adapted these techniques to measure subcellular calcium dynamics within a damaged and regenerating neuron in C. elegans. By laser severing and imaging a neuron expressing calcium sensitive G-CaMP, they have identified sustained sub-cellular calcium signals and the cellular components modulating them which are critical to efficient regeneration. Moreover employing optogenetic light activated channels the Gabel lab was able to manipulate these signals enhancing the neurons regenerative capacity (Sun et al. J. Neuroscience 2014). Thus using modern neurophotonics the Gabel lab can effectively damage an individual neuron, measure its physiological response and modulate that response to improve neuronal recovery.

Calcium fluorophores are also employed to measure neuronal activity, with indicators reporting the elevation of cellular calcium resulting from neuronal depolarization. The Gabel lab has recently developed techniques to measure neuronal activity in C. elegans within pathological context such as physical damage and age related decline. In collaboration with Professor Chris Connor (Dept. of Anesthesiology, Brigham and Women’s Hospital, Harvard University), the lab recently acquired a diSPIM light sheet microscope capable of fast volumetric imaging of the entire head of C. elegans. The small size of its nervous system and cell specific expression of calcium indicators allows imaging of individual neurons, specific well-defined circuits controlling behavior or the activity across the majority of the nervous system with single cell resolution.

Work with Dr. Connor is focused on the effects of volatile anesthetics on neuronal function. Despite their prevalence in modern medicine the mode of action of volatile anesthetics on the nervous system is largely unknown. In addition, they present poorly defined risks to the development of the very young and to sustained cognition in the very old. C. elegans is an established model system in the search for anesthetic receptors and displays behavioral phases of anesthetization similar to humans. Functional neuronal imaging in C. elegans presents an opportunity to understand how volatile anesthetics disrupt neuronal function in a controlled and reversible manor. In a recent study performed by Mehraj Awal, a graduate student in Physiology and Biophysics and NRT fellow, the group showed that neurons within a highly ordered sub-circuit of C. elegans controlling behavior becomes disorganized and hyperactive with the onset of anesthesia (Awal et al. Anesthesiology 2018). More recently Greg Wirak, a GPN student and NRT fellow in the lab, has discovered that exposure to volatile anesthetics during development altars the neuronal dynamics of key interneurons in the adult animal. These findings open a new window into the potential health risks of anesthetics in the very young. Moving forward the Gabel lab is working to expand these techniques to pan-neuronal imaging across the majority of neurons in the animal’s head, in order to understand the effects of volatile anesthetics on a systems level and how this correlates with measurements made on human patients (EEGs).

Selected Publications:

Sun L., Shay J, McLoed M., Roodhouse K., Chung S.H., Clark C., Alkema M. and Gabel C.V., “Neuronal Regeneration in C. elegans Requires Sub-cellular Calcium Release by Ryanodine Receptor Channels and Can Be Enhanced by Optogenetic Stimulation.”, J. Neuroscience, 34(48):15947-56. doi: 10.1523, 2014

Gruner M., Nelson D., Hintz R., Chung S.H., Gabel C.V., van der Linden A., “Feedback Modulation of Chemoreceptor Gene Expression Mediated by Feeding State and NPR-1”, PLOS Genetics, 10(10): e1004707. doi: 10.1371, 2014

Chung S., Schmalz A, Ruiz R.C., Gabel C.V.#, Mazur E. “Femtosecond Laser Ablation Reveals Antagonistic Sensory and Neuroendocrine Signaling that Underlie C. elegans Behavior and Development.” Cell Reports, 4(2):316-26. doi: 10.1016/j.celrep.2013.06.027, 2013 (#corresponding author)

Chung S., Sun L., Gabel C. V., “In vivo neuronal calcium imaging in C. elegans”, Journal of Visualized Experiments (JoVE), 10;(74). doi: 10.3791/50357, 2013

Kim E., Sun L., Gabel C. V., and Fang-Yen C., “Long-term imaging of Caenorhabditis elegans using nanoparticle-mediated immobilization”, PLoS ONE 8(1): e53419. doi:10.1371/journal.pone.0053419, 2013

Pinan-Lucarre B.*, Gabel C. V.*#, Reina C. P., Hulme S. E., Shevkoplyas S. S., Slone R. D., Xue1 J., Qiao Y., Weisberg S., Roodhouse K., Sun L., Whitesides G. M., Samuel A. D. T.#, Driscoll M. “The Core Apoptotic Executioner Proteins CED-3 and CED-4 Promote Initiation of Neuronal Regeneration in Caenorhabditis elegans”, PLoS Biology, 10(5):e1001331, 2012 (* co-first authors, #corresponding authors)

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

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

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

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

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

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Contact Us

Department of Pharmacology, Physiology & Biophysics
Chobanian & Avedisian School of Medicine
700 Albany Street, W302C
Boston MA 02118-2526

Phone:(617) 358-8461
e-mail: cvgabel@bu.edu