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Institute research projects feature statistical, mathematical or computational modeling of biological systems at all levels of complexity, from molecules to ecosystems. All projects are interdisciplinary in nature, conducted by individuals or teams of individuals who combine knowledge of biology with analytic approaches from mathematics, physics or engineering.

Interdisciplinary collaborations among QBI members

·         Rowe (BIOS), Neiman (PHYS) and Peterson (BIOS).  Collaboration to study response properties of vestibular afferents in terms of information theory.  Pending NIH grant “Encoding of natural signals by vestibular neurons:  Information analysis”, Rowe, PI.

·         Neiman (PHYS) and Peterson (BIOS).  Modeling studies of vestibular hair cells to determine how various ionic conductances shape the response of vestibular hair cells to mechanical stimulation.

·         Peterson (BIOS), Rowe (BIOS) and Neiman (PHYS).  Mechanism of signaling in otoconial organs.  Pending NIH grant, Peterson PI.

·         Rowe (BIOS) and Jung (PHYS).  Modeling the biophysical properties of retinal neurons, particularly stimulus induced synchrony in retina and lateral geniculate.

Interdisciplinary collaborations between QBI members and other Ohio University researchers

·         Neiman (PHYS) and Russell (BIOS).  The functional significance of oscillations in sensory systems using electroreceptors in paddlefish as an experimental model.  Grant “Stochastic nonlinear dynamics of sensory nervous systems” awarded, Russell, PI.

·         Holmes (BIOS-modeler), Colvin, Li, and Lee (BIOS and BIOMED-experimental).  Models of zinc homeostasis as a target of drug action in the CNS.  Grant pending, Colvin, PI. 

·         Just (MATH) and Morris (BIOS).  Modeling game-theoretic animal interactions.

·         Tees (PHYS) and Goetz (CHE). Leukocyte adhesion biophysics, including studies on leukocyte adhesion in a micropipette that models leukocyte arrest in capillaries.

·         Tees (PHYS), Kieliszewski (CHEM), Welch (EECS), Showalter (EPB) and Faik (EBP).  Single molecule forced unbinding of plant cell wall glycoproteins.  Grants pending with Showalter, PI and Faik, PI.

·         Neiman (PHYS), Russell (BIOS), Govorov (PHYS) and Richardson (CHEM).  Using gold nanoparticles as actuators of neuronal dynamics.  Grant “Control of cell systems using optically-driven nanoparticles as non-destructive actuators”, Russell PI, pending.

Interdisciplinary collaborations between QBI members and researchers from other institutions

·         Neiman (PHYS) and Tass (Institute of Medicine, Research Center Juelich Germany).  Mechanisms of stochastic synchronization and desynchronization of neuronal oscillators.  This project is devoted to theoretical and experimental validation of novel approaches for deep brain stimulation for treatment of Parkinson’s disease developed in Juelich.

·         Peterson (BIOS), Rowe (BIOS) and Grant (Virginia Tech, Engineering).  Biomechanics of vertebrate hair cells:  Experimental and computational analysis.  NIH grant, Peterson, PI. 

·         Young (MATH) and Boczko (Vanderbilt, Biomedical Informatics).  A new paradigm in binary classification and application to genomic and proteomic data. 

·         Jung (PHYS) and Brown (formerly BIOS, now Ohio State, Neuroscience). Modeling slow axonal transport. Collaborative NSF/NIH grant pending, Brown, PI.

·         Holmes (BIOS-modeler) and Grover (Marshall, Physiology-experimentalist).  Models of signaling mechanisms in LTP.  NIH grant, Holmes, PI.

·         Jung (PHYS) and Machaca (U. Arkansas Medical Sciences).  Calcium signaling differentiation during oocyte maturation.


Dynamic synchronization of Retinal Neurons
Rowe, Jung

Retinal circuitry creates a neural representation of the image formed by the eye and encodes this representation in the spike trains of optic nerve fibers. There is growing evidence that individual optic nerve fibers do not act as independent information channels. Spikes in two or more optic nerve fibers become precisely synchronized when presented with a common visual stimulus, and the time scale of this synchronization is 1-2 orders of magnitude less than either the temporal structure of the stimulus or the integration time of the visual system. Such synchronization has been reported to occur over both small and large spatial scales. The synchronization over large spatial scales may be a manifestation of a population coding scheme for representing the spatial structure of the image. Synchronization over small spatial scales may be utilized within the brain to extract signals from noisy spike trains. This project is designed to understand how networks of retinal neurons are able to generate a synchronized output to the brain.

Vestibular Neuroscience and Hair Cell Biomechanics

red and green confocal of cristaAll vertebrates rely on the vestibular system to maintain balance and clear vision during normal behavior. Yet in spite of its central role in behavior, the vestibular system is one of our most poorly understood senses. At its most basic level, the vestibular system can be thought of as a pair of three-neuron arcs that link sensory receptors in the inner ear (hair cells in ampullae and otolith organs) with motor neurons that control neck and limb muscles (see figure) or eye muscles (not illustrated). These three-neuron arcs provide simple but powerful experimental models for analyzing sensorimotor trans-formations and motor learning.
Our experiments use an in vitro whole-brain preparation that includes the inner ear, brainstem, and neck musculature (see figure). This preparation allows us to study intact neurons and neural circuits that transform sensory signals into motor commands. Current studies focus on two subjects. (1) We analyze the neuronal circuits that stabilize posture and gaze using experimental electron microscopy and light microscopy of
anatomically and physiologically characterized neurons. (2) We use light and electron microscopy, computermodels, and laser interferometry to understand how vestibular hair cells detect head movement.

Stochastic Model of Glutamate Release at a Synapse

Small blue balls grouped into a larger ball represent glutamate molecules in a synaptic vesicleThe goal of my research is to develop mathematical and computational models of individual neurons of the hippocampus that will be appropriate for use in network models. The immediate focus is to develop highly detailed models of dentate granule cells that describe appropriately how computation and synaptic modification occur in these cells. These highly detailed models must satisfy the constraints imposed by experimental data including conditions leading to long-term potentiation (LTP) and long-term depression (LTD).

Modeling work is proceeding on molecular, synaptic and neuron levels. On the molecular level, a model of a dendritic spine is being extended to include calcium binding to calmodulin and calmodulin binding and trapping by CaM-kinase II with the hope of being able to express the essence of these biochemical reactions in a synaptic modification rule. On the synaptic level, diffusion models of the synaptic cleft have been developed to determine more accurate descriptions of NMDA and AMPA conductances for use in neuron level models. On the neuron level, detailed morphology is being used in simulations to determine the range of computational possibilities of neurons as constrained by the spatial and temporal distribution of synaptic and non-synaptic conductances. Methods are being developed to determine appropriate parameter values for the conductances.

Calcium signaling differentiation during oocyte maturation.

Jung and Machaca (U. Arkansas Medical Sciences)

During oocyte maturation, restructuring of ER and redistribution of Ca2+ signaling machinery leads to changes in the signaling mode that reflects the requirements of the signaling apparatus toward successful and reliable fertilization.  Using computational modeling of Ca2+ signaling in the developing oocyte in conjunction with detailed experimental assessment of the distributions of channels and receptors throughout development through immunostaining we attempt to understand the role of spatial arrangements and affinities for Ca2+ signaling. 



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