The Eugene Bell Center for Regenerative Biology and Tissue Engineering

East Falmouth, Massachusetts, United States

The Eugene Bell Center for Regenerative Biology and Tissue Engineering

East Falmouth, Massachusetts, United States

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Smith J.,The Eugene Bell Center for Regenerative Biology and Tissue Engineering | Morgan J.R.,University of Texas at Austin | Zottoli S.J.,Williams College | Zottoli S.J.,The Marine Biological Laboratory | And 4 more authors.
Biological Bulletin | Year: 2011

What gives an organism the ability to regrow tissues and to recover function where another organism fails is the central problem of regenerative biology. The challenge is to describe the mechanisms of regeneration at the molecular level, delivering detailed insights into the many components that are cross-regulated. In other words, a broad, yet deep dissection of the system-wide network of molecular interactions is needed. Functional genomics has been used to elucidate gene regulatory networks (GRNs) in developing tissues, which, like regeneration, are complex systems. Therefore, we reason that the GRN approach, aided by next generation technologies, can also be applied to study the molecular mechanisms underlying the complex functions of regeneration. We ask what characteristics a model system must have to support a GRN analysis. Our discussion focuses on regeneration in the central nervous system, where loss of function has particularly devastating consequences for an organism. We examine a cohort of cells conserved across all vertebrates, the reticulospinal (RS) neurons, which lend themselves well to experimental manipulations. In the lamprey, a jawless vertebrate, there are giant RS neurons whose large size and ability to regenerate make them particularly suited for a GRN analysis. Adding to their value, a distinct subset of lamprey RS neurons reproducibly fail to regenerate, presenting an opportunity for side-by-side comparison of gene networks that promote or inhibit regeneration. Thus, determining the GRN for regeneration in RS neurons will provide a mechanistic understanding of the fundamental cues that lead to success or failure to regenerate. © 2011 Marine Biological Laboratory.


PubMed | The Eugene Bell Center for Regenerative Biology and Tissue Engineering, University of California at Los Angeles, University of Texas at Austin and University of Duisburg - Essen
Type: | Journal: Experimental neurology | Year: 2016

Spinal cord injury causes neuronal death, limiting subsequent regeneration and recovery. Thus, there is a need to develop strategies for improving neuronal survival after injury. Relative to our understanding of axon regeneration, comparatively little is known about the mechanisms that promote the survival of damaged neurons. To address this, we took advantage of lamprey giant reticulospinal neurons whose large size permits detailed examination of post-injury molecular responses at the level of individual, identified cells. We report here that spinal cord injury caused a select subset of giant reticulospinal neurons to accumulate synuclein, a synaptic vesicle-associated protein best known for its atypical aggregation and causal role in neurodegeneration in Parkinsons and other diseases. Post-injury synuclein accumulation took the form of punctate aggregates throughout the somata and occurred selectively in dying neurons, but not in those that survived. In contrast, another synaptic vesicle protein, synaptotagmin, did not accumulate in response to injury. We further show that the post-injury synuclein accumulation was greatly attenuated after single dose application of either the molecular tweezer inhibitor, CLR01, or a translation-blocking synuclein morpholino. Consequently, reduction of synuclein accumulation not only improved neuronal survival, but also increased the number of axons in the spinal cord proximal and distal to the lesion. This study is the first to reveal that reducing synuclein accumulation is a novel strategy for improving neuronal survival after spinal cord injury.


Graham D.M.,The Eugene Bell Center for Regenerative Biology and Tissue Engineering | Messerli M.A.,The Eugene Bell Center for Regenerative Biology and Tissue Engineering | Messerli M.A.,National Oceanic and Atmospheric Administration | Pethig R.,National Oceanic and Atmospheric Administration | Pethig R.,University of Edinburgh
BioTechniques | Year: 2012

The selection, isolation, and accurate positioning of single cells in three dimensions are increasingly desirable in many areas of cell biology and tissue engineering. We describe the application of a simple and low cost dielectrophoretic device for picking out and relocating single target cells. The device consists of a single metal electrode and an AC signal generator. It does not require microfabrication technologies or sophisticated electronics. The dielectrophoretic manipulator also discriminates between live and dead cells and is capable of redistributing intracellular organelles.


Messerli M.A.,The Eugene Bell Center for Regenerative Biology and Tissue Engineering | Messerli M.A.,National Oceanic and Atmospheric Administration | Graham D.M.,The Eugene Bell Center for Regenerative Biology and Tissue Engineering
Biological Bulletin | Year: 2011

Endogenous DC electric fields (EFs) are important, fundamental components of development, regeneration, and wound healing. The fields are the result of polarized ion transport and current flow through electrically conductive pathways. Nullification of endogenous EFs with pharmacological agents or applied EFs of opposite polarity disturbs the aforementioned processes, while enhancement increases the rate of wound closure and the extent of regeneration. EFs are applied to humans in the clinic, to provide an overwhelming signal for the enhancement of healing of chronic wounds. Although clinical trials, spanning a course of decades, have shown that applied EFs enhance healing of chronic wounds, the mechanisms by which cells sense and respond to these weak cues remains unknown. EFs are thought to influence many different processes in vivo. However, under more rigorously controlled conditions in vitro, applied EFs induce cellular polarity and direct migration and outgrowth. Here we review the generation of endogenous EFs, the results of their alteration, and the mechanisms by which cells may sense these weak fields. Understanding the mechanisms by which native and applied EFs direct development and repair will enable current and future therapeutic applications to be optimized. © 2011 Marine Biological Laboratory.


PubMed | The Eugene Bell Center for Regenerative Biology and Tissue Engineering, University of South Florida and Stanford University
Type: Journal Article | Journal: The Journal of experimental biology | Year: 2016

Swimming animals commonly bend their bodies to generate thrust. For undulating animals such as eels and lampreys, their bodies bend in the form of waves that travel from head to tail. These kinematics accelerate the flow of adjacent fluids, which alters the pressure field in a manner that generates thrust. We used a comparative approach to evaluate the cause-and-effect relationships in this process by quantifying the hydrodynamic effects of body kinematics at the body-fluid interface of the lamprey, Petromyzon marinus, during steady-state swimming. We compared the kinematics and hydrodynamics of healthy control lampreys to lampreys whose spinal cord had been transected mid-body, resulting in passive kinematics along the posterior half of their body. Using high-speed particle image velocimetry (PIV) and a method for quantifying pressure fields, we detail how the active bending kinematics of the control lampreys were crucial for setting up strong negative pressure fields (relative to ambient fields) that generated high-thrust regions at the bends as they traveled all along the body. The passive kinematics of the transected lamprey were only able to generate significant thrust at the tail, relying on positive pressure fields. These different pressure and thrust scenarios are due to differences in how active versus passive body waves generated and controlled vorticity. This demonstrates why it is more effective for undulating lampreys to pull, rather than push, themselves through the fluid.


PubMed | The Eugene Bell Center for Regenerative Biology and Tissue Engineering
Type: Journal Article | Journal: The Biological bulletin | Year: 2011

Endogenous DC electric fields (EFs) are important, fundamental components of development, regeneration, and wound healing. The fields are the result of polarized ion transport and current flow through electrically conductive pathways. Nullification of endogenous EFs with pharmacological agents or applied EFs of opposite polarity disturbs the aforementioned processes, while enhancement increases the rate of wound closure and the extent of regeneration. EFs are applied to humans in the clinic, to provide an overwhelming signal for the enhancement of healing of chronic wounds. Although clinical trials, spanning a course of decades, have shown that applied EFs enhance healing of chronic wounds, the mechanisms by which cells sense and respond to these weak cues remains unknown. EFs are thought to influence many different processes in vivo. However, under more rigorously controlled conditions in vitro, applied EFs induce cellular polarity and direct migration and outgrowth. Here we review the generation of endogenous EFs, the results of their alteration, and the mechanisms by which cells may sense these weak fields. Understanding the mechanisms by which native and applied EFs direct development and repair will enable current and future therapeutic applications to be optimized.


PubMed | The Eugene Bell Center for Regenerative Biology and Tissue Engineering
Type: Journal Article | Journal: BioTechniques | Year: 2012

The selection, isolation, and accurate positioning of single cells in three dimensions are increasingly desirable in many areas of cell biology and tissue engineering. We describe the application of a simple and low cost dielectrophoretic device for picking out and relocating single target cells. The device consists of a single metal electrode and an AC signal generator. It does not require microfabrication technologies or sophisticated electronics. The dielectrophoretic manipulator also discriminates between live and dead cells and is capable of redistributing intracellular organelles.

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