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Role of RGS proteins on the
desensitization of G protein signaling in yeast
Necmettin Yildirim, Nan Hao, Henrik G. Dohlman
and Tim Elston
Like human beings, a cell needs to communicate with its neighbors to
maintain its life. When a stimulus reaches to its surface, the receptors
located in the membrane give response and relay information to the
internal component of the cell and trigger some specific pathways which
often rely up to the nucleus and affect the transcription process. This is
known as cell signaling. The source of the stimulus might be coming
from the organism itself, such as neurotransmitters and hormones, or from
its environment and like drugs.
The common property of the cell signaling is that it is subject to
desensitization to prolonged stimulus. Most of the studies of regulation
on desensitization have focused on the membrane receptors. We will
investigate the role of regulators of G protein signaling (RGS) on the
desensitization and also work on how the delays due to the transcription
and translation processes effect on this desensitization..
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Modeling the movement of Flagellar
dynein
Mike Goedecke and Tim Elston
Motor proteins convert chemical energy into
useful physical work inside a cell.For example, ATP synthetase utilizes a
proton gradient to produce ATP from ADP and PO4, actin and myosin work
together to provide muscle contraction, and proteins such as kinesin and
dynein hydrolyze ATP to transport vesicles and organelles within a cell.
Some types of dynein are responsible for the beating of eukaryotic cilia
and flagella, thus enabling sperm cells to swim and epithelial cells to
clear irritants from the repiratory tract.
By using laser traps, experimentalists can
now manipulate and record data from a single molecule of a motor protein.
I have been modelling the movement of a type of flagellar dynein isolated
from sea urchin sperm in an effort to combine chemical rate data from ATP
hydrolysis with a plausible physical cycle of dynein motion.
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Mathematical modeling of
biochemical
networks
Peiying Zuo and Tim Elston
The adjustment of the
elements that control mucus transport, i.e., ion transport/ASL volume,
cilia beat frequency, and mucin secretion, is complex and poorly
understood. It is clear that nucleotide metabolism plays a critical role
through, for example, the concentration of ATP and adenosine via
interaction with specific cell surface receptors. In this project, many
details of nucleotide metabolism are codified into a mathematical
framework. Further, we need to expand an initial metabolic model to
include the biochemical control of ion transport and water, mucus
secretion and cilia beat parameters.
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Modeling the transcriptional
enhancement of inducible
eukaryotic protein coding genes
Jason R. Pirone and Tim Elston
Thousands of transcription factors have been identified, as have the
enhancer/promoter regions of a myriad of genes. Despite this wealth of
information, there is still considerable debate surrounding the fundamental
mechanism of enhancer action. Changes in transcription level following
activation could be due to either an alteration in the rate of transcription
by RNA Polymerase II (graded response) or a change in the probability of the
promoter being active (binary response). The binary model predicts that the
initial cell population transitions from the low to high state directly,
resulting in a bimodal transition that reflects depopulation of the low
state and concomitant opulation of the high state. The animation shows
the time evolution of the probability density function of a tetrameric
reporter protein. The x-axis represents nondimensionalized tetramer
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Investigation of the immune system
response to the influenza virus
Abby Todd, Kevin Morgan (Aventis), Lynn Crosby
and Tim Elston
The project is a joint project with a group of biologists on connecting a
mathematical model of the immune system to real life data. We have
taken a simple mathematical model detailing the response of cytotoxic
T-lymphocytes to infected cells and are expanding this model to include
helper T cells, B cells, antibodies, free virus, and macrophages. We
will focus on the immune response to the influenza virus. |
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Calcium signaling in plants
Jingfang Huang, Zhen-Ming Pei (Duke
Univeristy) and Tim Elston
This project has three subtitles:
A. Randomness of the ion channels
Every ion channel is described by a stochastic differential equatioin with
different coefficient. To simulate the stochastic differential equations, we
propose a new class of SDE initial value problem solver based on integral
equation method and compare it with many of the existing classical
techniques. |
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B. Diffusion Equation Solver
The concentration within the cytosol is
governed by the left diffusion equation up to a diffusion coefficient.
To accurately and efficiently simulate this process, we introduce the
fast diffusion equation solver based on fast Gauss transform, integral
equation methods and diagonal translation operators.
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C. Image Analysis
Biological experiments provide various data from
which we can extract the calcium concertration of every point in the domain
at some time interval as shown in the left figure. The goal of image
analysis is to extract Ca2+ current for all times for the ion channels from
these image files, which is then used to determine the parameters in the
sotchastic and diffusion models. Here, we proposed an image processing
package based on the solutioin of the diffusion equation. The Ca2+ currents
can then be determined by studying the "flux" of the concentration, or its
gradient. |
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