Seminars and Colloquia by Series

Stabilization of multimeric enzymes: structural adaptation to stress conditions

Series
Mathematical Biology Seminar
Time
Wednesday, March 25, 2009 - 11:00 for 1 hour (actually 50 minutes)
Location
Skiles 255
Speaker
Ruslan RafikovMedical College of Georgia
The stress condition calls for an adequate activity of key enzymatic systems of cellular defense. Massive protein destabilization and degradation is occurring in stressed cells. The rate of protein re-synthesis (DNA->RNA->protein) is inadequate to adapt to rapidly changing environment. Therefore, an alternative mechanism should exist maintaining sufficient activity of defense enzymes. Interestingly, more than 50% of enzymes consist of identical subunits which are forming multimeric interface. Stabilization of multimers is important for enzymatic activity. We found that it can be achieved by the formation of inter-subunit covalent bridges in response to stress conditions. It shows an elegance of the structure design that directs selective subunits linkage and increases enzyme's robustness and chances of cell survival during the stress. In contrast, modification of aminoacids involved in linkage leads to protein destabilization, unfolding and degradation. These results describe a new instantaneous mechanism of structural adaptation that controls enzymatic system under stress condition.

"Feel Sick? Follow the money!" - New Perspectives on Global Human Mobility and Disease Dynamics

Series
Mathematical Biology Seminar
Time
Wednesday, March 11, 2009 - 11:00 for 1 hour (actually 50 minutes)
Location
Skiles 255
Speaker
Dirk BrockmannNorthwestern University
Human Mobility in our globalised world has reached a complexity and volume of unprecedented degree. More than 60 million people travel billions of kilometres on more than 2 million international flights each week. Hundreds of millions of people commute on a complex web of highways and railroads most of which operate at their maximum capacity. Human mobility is responsible for the geographical spread of emergent human infectious diseases and plays a key role in human mediated bioinvasion, the dominant factor in the global biodiversity crisis. I will report on the recent discovery of scaling laws in global human traffic (obtained from online bill-tracking at www.wheresgeorge.com) and mathematical models that can account for it. I will present a complex network perspective on multi-scale human traffic networks, report on their statistical properties and show that they can be used to identify geographically coherent communities that only vaguely resemble administrative ones. The approach provides an operational segmentation of maps into a hierarchical set of effective regions and boundaries based on human behavior. I will briefly talk about European transportation networks, geocaching and trackable items.

Analysis of a an Age-Structured Population Model with Monotone Birth Rate Function

Series
Mathematical Biology Seminar
Time
Wednesday, March 4, 2009 - 11:00 for 1 hour (actually 50 minutes)
Location
Skiles 255
Speaker
Sean Ellermeyer Kennesaw State University
We consider a class of age-structured population models in which the central modeling assumption is simply that the birth rate depends on the size of the adult population. For the most part, we in fact assume that the birth rate is a monotone non-decreasing function of the adult population size. Despite the simplicity of our modeling assumptions (or perhaps because of it), we will see that this class of models admits a wide variety of solutions (exponentially growing, lineary growing, periodic, etc.) Much of the analysis of these models can be carried out using elementary techniques and we present some specific examples in which explicit solutions (which are elementary functions) can be generated. We also consider some questions related to the inverse problem for these models.

Nonlinear effect of copy number variation on gene expression

Series
Mathematical Biology Seminar
Time
Wednesday, February 25, 2009 - 11:00 for 1 hour (actually 50 minutes)
Location
Skiles 255
Speaker
Yuriy MileykoSchool of Biology, Georgia Tech
The expression dynamics of interacting genes depends on the topology of the regulatory network, the quantitative nature of feedbacks and interactions between DNA, RNA and proteins, and the biochemical state of the intracellular and surrounding environment. In this talk we show that dynamics of a gene regulatory network can also depend sensitively on the copy number of genes and promoters. Genetic regulatory networks include an overrepresentation of subgraphs commonly known as network motifs. We consider positive feedback, bistable feedback, and toggle switch motifs and show that variation in gene copy number can cause a sequence of saddle-node bifurcations in the corresponding differential equations models, which leads to multiple orders of magnitude change in gene expression. A similar analysis of a 3-gene motif with successive inhibition (the ``repressilator'') reveals that changes in gene copy number can also cause a Hopf bifurcation, thus leading to a qualitative switch in system behavior among oscillatory and equilibrium dynamics. Importantly, we show that these bifurcations exist over a wide range of parameter values, thus reinforcing our claim that copy number is a key control parameter in the expression dynamics of regulatory networks.

Transient (Electro)Chemical Imaging of Reacting Interfaces - Physical Concepts and Mathematical Challenges

Series
Mathematical Biology Seminar
Time
Wednesday, December 3, 2008 - 11:00 for 1 hour (actually 50 minutes)
Location
Skiles 255
Speaker
Andrei FedorovSchool of Mechanical Engineering, Georgia Tech
In this presentation I will outline physical principles of two analytical techniques, the Scanning ElectroChemical Microscopy (SECM) and Scanning Mass Spectrometry (SMS), which can be used to obtain the spatially resolved images of (bio/electro)chemically active interfaces. The mathematical models need to be employed for image interpretation and mapping measured quantities (e.g., an electrode current in SECM) to biochemically relevant quantities (e.g., kinetics of exocytotic signaling events in cellular communications), and I will review the key ideas/assumptions used for the model formulation and the main results of analysis and simulations. In conclusion, an alternative approach to spatially-resolved imaging based on the multi-probe array will be introduced along with intriguing opportunities and challenges for mathematical interpretation of such images.

A Simple Quantitative Genetic Model of Parent-Offspring Interactions

Series
Mathematical Biology Seminar
Time
Wednesday, November 12, 2008 - 11:00 for 1 hour (actually 50 minutes)
Location
Skiles 255
Speaker
Benjamin Ridenhour CDC/CCID/NCIRD, CTR
Parent-offspring interactions lead to natural conflicts. Offspring want as many resources as possible from parents in order to gain maximal fitness levels. On the other hand, parents desire to invest only enough to guarantee survival to reproduction. The resolution of the parent-offspring conflict has been a topic of much debate in evolutionary biology and typically invoke the concept of 'costs' to begging by offspring. Here I present the analysis of a simple quantitative genetic model of parent-offspring interactions that does not costs to resolve parent-offspring conflicts.

Eat your spinach? The role of buffering reactions in clearing hydrogen

Series
Mathematical Biology Seminar
Time
Wednesday, November 5, 2008 - 11:00 for 1 hour (actually 50 minutes)
Location
Skiles 255
Speaker
Melissa KempDept of Biomedical Engineering, Georgia Tech
Hydrogen peroxide has been long considered a harmful reactive oxygen species, but is increasingly appreciated as a cellular signaling molecule. The mechanism by which the cell buffers against intracellular H2O2 accumulation during periods of oxidative stress is not fully understood. I will introduce a detailed network model of the known redox reactions and cellular thiol modifications involved in H2O2 buffering. The model includes anti-oxidative contributions of catalase, glutathione peroxidase, peroxiredoxin, and glutaredoxin, in addition to the cytoplasmic redox buffers, thioredoxin and glutathione. Based on ordinary differential equations, the model utilizes mass action kinetics to describe changes in concentration and redox state of cytoplasmic proteins upon exposure to physiologically relevant concentrations of extracellular H2O2. Simulations match experimental observations of a rapid and transient oxidation of thioredoxin upon exposure to extracellular peroxide. The increase in the concentration of oxidized proteins predicted by the model is simultaneously accompanied by an increase in protein S-glutathionylation, possibly regulating signal transduction in cells undergoing oxidative stress. Ultimately, this network analysis will provide insight into how to target antioxidant therapies for enhanced buffering without impacting the necessary protein oxidation used by cells for signaling purposes.

Data-driven methods in protein engineering: new ways to utilize sequence and structures of proteins

Series
Mathematical Biology Seminar
Time
Wednesday, October 22, 2008 - 11:00 for 1 hour (actually 50 minutes)
Location
Skiles 255
Speaker
Andy BommariusSchool of Chemistry & Biochemistry, Georgia Tech
After rational protein design and combinatorial protein engineering (directed evolution), data-driven protein engineering emerges as a third generation of techniques for improving protein properties. Data-driven protein engineering relies heavily on the use of mathematical algorithms. In the first example, we developed a method for predicting the positions in the amino acid sequence that are critical for the catalytic activity of a protein. With nucleotide sequences of both functional and non-functional variants and a Support Vector Machine (SVM) learning algorithm, we set out to narrow the interesting sequence space of proteins, i.e. find the truly relevant positions. Variants of TEM-1 β-lactamase were created in silico using simulations of both mutagenesis and recombination protocols. The algorithm was shown to be able to predict critical positions that can tolerate up to two amino acids. Pairs of amino acid residues are known to lead to inactive sequences, unless mutated jointly. In the second example, we combine SVM, Boolean learning (BL), and the combination of the two, BLSVM, to find such interactive residues. Results on interactive residues in two fluorescent proteins, Discosoma Red Fluorescent Protein (Ds-Red) and monomeric Red Fluorescent Protein (mRFP), will be presented.

Dynamics and implications of some models of hepatitis B virus infection

Series
Mathematical Biology Seminar
Time
Wednesday, October 15, 2008 - 11:00 for 1 hour (actually 50 minutes)
Location
Skiles 255
Speaker
Yang KuangArizona State University
Chronic HBV infection affects 350 million people and can lead to death through cirrhosis-induced liver failure or hepatocellular carcinoma. We present the rich dynamics of two recent models of HBV infection with logistic hepatocyte growth and a standard incidence function governing viral infection. One of these models also incorporates an explicit time delay in virus production. All model parameters can be estimated from biological data. We simulate a course of lamivudine therapy and find that the models give good agreement with clinical data. Previous models considering constant hepatocyte growth have permitted only two dynamical possibilities: convergence to a virus free or an endemic steady state. Our models admit periodic solutions. Minimum hepatocyte populations are very small in the periodic orbit, and such a state likely represents acute liver failure. Therefore, the often sudden onset of liver failure in chronic HBV patients can be explained as a switch in stability caused by the gradual evolution of parameters representing the disease state.

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