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
(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.
(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.
(BIOS), Rowe (BIOS) and Neiman (PHYS).
Mechanism of signaling in otoconial organs. Pending NIH grant, Peterson PI.
(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
(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.
(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,
(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.
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.
(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
(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.
(BIOS), Rowe (BIOS) and Grant (Virginia Tech, Engineering). Biomechanics of vertebrate hair cells: Experimental and computational
analysis. NIH grant, Peterson,
(MATH) and Boczko (Vanderbilt, Biomedical Informatics). A new paradigm in binary classification and
application to genomic and proteomic data.
(PHYS) and Brown (formerly BIOS, now Ohio State,
Neuroscience). Modeling slow axonal transport. Collaborative NSF/NIH grant
pending, Brown, PI.
(BIOS-modeler) and Grover (Marshall, Physiology-experimentalist). Models of signaling mechanisms in LTP. NIH grant, Holmes, PI.
(PHYS) and Machaca (U. Arkansas
Medical Sciences). Calcium signaling
differentiation during oocyte maturation.
RESEARCH PROJECTS IN MORE DETAIL
Dynamic synchronization of Retinal Neurons
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
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
The 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
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