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NIMBioS Seminars (Feb - Mar 2009)

NIMBioS is sponsoring seminars on a range of topics at the interface of mathematics and biology. Seminars are open to the public. Anyone interested in meeting with the speakers should contact Dr. Chris Welsh. Meeting times and locations are subject to change, so please check this site prior to attending a seminar.

Time: Thu 2/19 11:00-12:00
Location: M307 Walters Life Sciences Bldg.
Speaker: Degui Zhi, Plant and Microbial Biology, UC Berkeley. Dr. Zhi earned his Ph.D. in bioinformatics from the University of California, San Diego. His main research interests include analysis of protein structure and computational genomics.
Topic: Protein structural comparison, classification, and function prediction in the structural genomics era
Abstract: Enormous structural data generated by structural genomics efforts create new challenge and opportunities. From a computational and mathematical point of view, I will discuss three topics: (i) fast and flexible structural comparison; (ii) evolutionary classification of proteins based on structure; and (iii) protein function prediction based on structure.

Time: Tue 2/24 1:30-2:30
Location: 307 Nielsen Physics Bldg
Speaker: Jaewook Joo, Computational Systems Biology Dept., Sandia National Laboratories, Albuquerque, NM.
Topic: A poor man's explanation of noise-induced cellular response in single cells
Abstract: Cells use various biological regulatory networks to detect and process external signals, and regulate their response in a noisy intracellular environment. As a consequence, the cellular response at the level of single cells is noisy, heterogeneous, and even individualistic. It is a paramount challenge of mathematical biology and possibly of great medical importance to elucidate and even predict the noisy cellular response in single cells. In this talk, I will present a poor man's explanation of noise-induced cellular response in single cells, using the example of NF-kB signal transduction networks.

Time: Thu 2/26 10:15-11:15
Location: 511 Buehler
Speaker: Rongsong Liu, Dept. Mathematics, Purdue Univ.
Topic: Plant-herbivore interactions mediated by plant toxicity
Abstract: We explore the impact of plant toxicity on the dynamics of a plant-herbivore interaction, such as that of a mammalian browser and its plant forage species, by studying a mathematical model that includes a toxin-determined functional response. In this functional response, the traditional Holling Type 2 response is modified to include the negative effect of toxin on herbivore growth, which can overwhelm the positive effect of biomass ingestion at sufficiently high plant toxicant concentrations. A detailed bifurcation analysis of the system reveals a rich array of possible behaviors including cyclical dynamics through Hopf bifurcations and homoclinic bifurcation.

Time: Fri 2/27 10:00-11:30
Location: 205 Claxton
Speaker: Jian Ma, Center for Biomolecular Science and Engineering, University of California at Santa Cruz
Topic: Reconstructing the evolutionary history of mammalian genomes
Abstract: Data generated from numerous mammalian genome sequencing projects have provided an unprecedented opportunity to use comparative genomics to computationally reconstruct the trajectory of all the genetic changes leading to modern placental mammals since their common ancestor living approximately 100 million years ago. However, this task is algorithmically extremely challenging. On a small scale, genomes have undergone point mutations, small insertions and deletions. More dramatically, at a larger scale, rearrangements, duplications, large insertions and deletions have led to varied karyotypes. In this talk, I will first introduce the method of contiguous ancestral regions, which reconstructs the ancestral karyotype based on modern species. Then I will discuss a recent work on reconstructing evolutionary histories involving complex operations on genomes, called the infinite sites model of genome evolution, which combines rearrangements, large insertions and deletions, and duplications into a single, computationally tractable model. Finally, I will discuss a number of ongoing projects and future plans in order to more efficiently and more accurately document the detailed changes in genome evolution, and to discover how evolution has shaped us at the molecular level.

Time: Mon 3/2 10:00-11:00
Location: 156/157 Plant Biotech. Bldg.
Speaker: Linda Highfield, Dept. Veterinary Integrative Biosciences, Texas A&M Univ.
Topic: The potential role of wildlife in the spread and control of Foot and Mouth disease in an extensive livestock management system.
Abstract: TBA

Time: Mon 3/2 1:00-2:30
Location: 511 Buehler
Speaker: Liang Liu, Dept. Organismic and Evolutionary Biology, Harvard Univ.
Topic: Estimating species phylogenies under the coalescence model
Abstract: Estimating the evolutionary history of species is one of the most important problems in evolutionary biology and recently there has been greater appreciation of the need to estimate species trees directly, other than using gene trees as a surrogate. In this talk, I will introduce three approaches for estimating species phylogenies from multilocus data under the coalescence model. The Bayesian approach, known as BEST, uses the full dataset to infer the species phylogeny, while the other two approaches (STAR and STEAC) use only partial information of the dataset. All three approaches can consistently estimate species phylogenies. Since the Bayesian approach involves intensive computation, it is impossible to use it to analyze large-scale genomic data which may include thousands of genes. By contrast, STAR and STEAC are based on summary statistics of coalescence times which are easy to compute and thus are suitable for the phylogenetic analysis of large-scale genomic data.

Time: Wed 3/4 12:00-1:30
Location: 511 Buehler
Speaker: Brian O'Meara, National Evolutionary Synthesis Center
Topic: Developing and applying tools to answer outstanding biological questions using phylogeni
Abstract: The creation and application of new methods to phylogenies and data now allow many questions about how organisms evolve to be addressed. I will discuss some of the new techniques I have developed and used, my work at NESCent on ways to move the field forward, and current and future research in looking at evolutionary rates and more realistic models of evolution. Empirical case studies will come from my own work on ants and from work by colleagues on fish, flies, and flowers.

Time: Wed 3/4 3:30-5:00
Location: A-118 VTH (Voss Veterinary Teaching Hospital)
Speaker: Seyed Moghadas, Institute for Biodiagnostics, National Research Council, Canada
Topic: Dynamics of resistance emergence in influenza infection with compensatory mutations
Abstract: Evolutionary responses of influenza viruses invoke strategies to escape the pressures that limit their replication and spread. Compensatory mutations are among well-known responses that can result in the generation of escape mutants from immune recognition or emergence of highly transmissible drug resistant viruses. In this talk, by developing a mathematical model, I will investigate the role of these mutations in the evolution of resistance in the context of viral-immune dynamics. Model simulations, using parameter estimates reported in the published literature, suggest that resistance is unlikely to emerge without compensation for the large fitness cost associated with the initial rise of resistant mutants. The results show that, in the absence of virus-specific immune memory, the time for start of treatment and the efficacy of drugs in suppressing viral replication are critical measures in the invasion of compensated mutants. However, pre-existing immune responses can irresistibly impede viral replication and prevent the outgrowth of resistance, regardless of treatment regimens. While uncertainties of parameter values pertaining to the in vivo dynamics remain to be addressed, the findings suggest that the presence of immune memory may be a key factor in preventing lethal consequences of infection.

Time: Mon 3/9 11:00-12:00
Location: M311 Walters Life Science Bldg.
Speaker: Hong Qin, Dept. Agricultural & Environmental Science, Tuskegee Univ.
Topic: Studying yeast aging through natural variation, statistical inference and mathematical modeling
Abstract: What are the natural causes of aging? We address this question by examining variation in life span of wild isolates of Saccharomyces cerevisiae. We found that genotypic variation accounts for about 22% of the total variation of replicative life span. Similar to aging in mammals, there is a negative correlation between the logarithmic transformation of the initial mortality rate and the Gompertz coefficient, which demonstrates that yeast aging and mammalian aging share the same characteristic at the demographic level. We then investigated whether increasing genomic instability and loss of mitotic asymmetry during aging is associated with natural variation in life span. We quantified chronological life span and loss-of-heterozygosity (LOH) in a collection of yeast natural isolates. We showed that genomic instability increases and mitotic asymmetry breaks down during chronological aging. The age-dependent increase of genomic instability generally lags behind the drop of viability and this delay accounts for ~50% of the observed natural variation of replicative life span in these yeast isolates. This suggests that the abilities of yeast strains to tolerate genomic instability co-vary with their replicative life spans. To the best of our knowledge, this is the first quantitative evidence that demonstrates a link between genomic instability and natural variation in life span. Finally, we developed a statistical and mathematical framework to address natural variation in yeast aging. This framework enabled us to demonstrate that there is a phase transition between the number of LOH events occurred in mother cells and those occurred in daughter cells. The existence of this phase transition provides insights on the age-induced switch to hyper-recombinational state in cellular aging.

Time: Mon 3/9 1:30-2:30
Location: A-118 VTH (Voss Veterinary Teaching Hospital)
Speaker: Paul Torgerson, Ross Univ. School of Veterinary Medicine
Topic: Echinococcus, math and public health. A complex conundrum or just plain common sense?
Abstract: Echinococcosis is a serious, emerging public health threat in several parts of the world. The collapse of the Soviet Union has lead to an epidemic of cystic echinococcosis in central Asia; ecological changes have resulted in increased numbers of human cases of alveolar echinococcosis in Europe and China. As model organisms, Echinococcus spp. present many questions in quantitative and qualitative analysis and in understanding the intricacies of infectious disease transmission. Despite the seeming simplicity of parasite transmission models, fitting data to these models has proved to be challenging. Qualitatively, the lack of a diagnostic gold standard has resulted in interesting complexities, whilst quantitatively highly aggregated parasite burdens pose additional difficulties. Using appropriate probability distributions and Bayesian analysis to model diagnostic uncertainty, valuable information can be gained and intervention strategies to control these diseases can be modeled, particularly in the resource poor communities where these parasites are highly endemic.

Time: Mon 3/9 3:35-4:35
Location: 102 Haslam Business Bldg.
Speaker: Shigui Ruan, Dept. Mathematics, Univ. of Miami
Topic: Nonlinear dynamics in structured epidemic models
Abstract: Mathematical models have been successfully used to study many infectious diseases and nonlinear and complex dynamics have been observed in those models. Structured epidemic models distinguish individuals from one another according to characteristics, such as age, location, status, and movement, to determine the interaction with each other and with environment, infectivity, etc. The goal of structured models is to understand how these characteristics affect the dynamics of these models and thus the outcomes and consequences of the epidemiological processes. In this talk we focus on two infectious diseases, malaria and influenza. We first show that different types of structured models, such as delay differential equation models, metapopulation models and reaction-diffusion equation models, can be used to study the transmission dynamics of malaria. Then by considering an age-structured type evolutionary epidemiological model of influenza A drift, we demonstrate that new theories need to be developed to understand the nonlinear dynamics of such models and the phenomenon of the seasonal/periodic reoccurrence of influenza.

Time: Thu 3/12 2:15-3:15
Location: 307 Science and Engineering Bldg.
Speaker: Vitaly Ganusov, Los Alamos National Laboratory
Topic: Modeling CD8 T cell dynamics following acute infections of mice
Abstract: Mathematical modeling is an emerging field of current immunology. In my talk I will review some of our recent work in which we have used mathematical models to address fundamental questions in immunology. Using the data on the CD8 T cell response to lymphocytic choriomeningitis virus (LCMV) in mice, I will demonstrate how one can use models to discriminate between different hypotheses on the generation of memory CD8 T cells following an acute viral infection. Using a novel technique of in vivo cytotoxicity, I will show that LCMV-specific effector and memory CD8 T cells on a per cell basis are equally efficient at killing peptide-pulsed targets in vivo. I will end by discussing areas of my future research.

Time: Thu 3/12 3:30-4:30
Location: M309 Walters Life Science Bldg.
Speaker: David Liberles, Dept. Molecular Biology, Univ. Wyoming, Laramie
Topic: Gene duplication, positive selection, & the evolution of gene function
Abstract: Gene duplication is an important process driving the evolution of genomes. Several fates have been proposed for duplicate genes, including neofunctionalization,subfunctionalization, dosage compensation, and selection for genetic robustness. Based upon expectations of duplicate gene retention versus dS and dN/dS rates versus dS under the various models, we evaluate the fates of duplicate genes en masse in the context of both smaller scale and whole genome duplication. Further, using both lattice and framework models of proteins with binding functions, evolution is simulated to characterize protein functional evolution after duplication. Specifically, we are interested in how positive selection via neofunctionalization as well as drift via subfunctionalization can drive the retention of duplicate copies and how this changes the functionality of the encoded protein model, as modulated by protein three dimensional structure. Turning from computational to experimental work, a model system will be described in the attempt to apply evolutionary principles to drug design. Phylogenetic analysis of sequence evolution following gene duplication is used in the GLP-1 gene family to design new agonists for potential use in Type II Diabetes. This is based upon the novel properties of a venom expressed GLP-1 homolog in gila monsters.

Time: Wed 3/25 1:30-3:00
Location: M307 Walters Life Science Bldg.
Speaker: Jian Liu, Dept. Molecular and Cell Biology, UC Berkeley
Topic: Mechanochemical feedbacks of cellular processes
Abstract: TBA



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NIMBioS is supported by the National Science Foundation through NSF Award #DBI-1300426, with additional support from The University of Tennessee, Knoxville. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.
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