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UBC Math Dept
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Mathematical Biology and related seminars

April, 2015
Tuesday,
April 21
Pavitra Roychoudhury -- 3:30 pm in ESB4133
Fred Hutchinson
Modelling single cells: applications for HIV cure and HSV immunology
Abstract
Individual-based models are widely used to describe the characteristics and dynamics of single organisms or particles in a population. A useful feature of these models is the ability to easily incorporate stochasticity and spatial structure at the individual level and, as a result, these models are well-suited to addressing questions in evolutionary biology and infectious diseases. In this talk, I will describe two models we have developed that incorporate these features. In the first project, we developed a stochastic, mechanistic model to predict the effectiveness and toxicity of therapies currently being developed to cause targeted disruption of latent viral genomes for the cure of diseases like HIV. We fit our model to flow cytometry data from multiple experiments aimed at optimizing engineered DNA cleavage enzymes delivered to cells using adeno-associated viruses (AAV) vectors. The model predicts the number of transgenes delivered, the level of expression and amount of cytotoxicity produced as a function of dosage for a given AAV serotype. We then use the model to predict the therapeutic index for a candidate therapeutic molecule and determine the optimal dosage, serotype and promoter for delivering the molecule to infected cells. In the second project, we developed a spatially structured, individual-based model of HSV spread in epithelial tissue with the goal of understanding how tissue-resident memory CD8+ T-cells (TRMs) control a reactivating HSV infection. CD8+ TRMs are a relatively recent discovery and characterizing their role and interactions with other T-cell compartments is vital for designing effective vaccine strategies against HSV. Our model incorporates mechanisms like viral diffusion, cell-cell spread, patrolling by TRMs, trafficking of effector memory T-cells (TEMs) from lymph nodes and effector functions of CD8s including tissue-wide alarm functions.
Tuesday,
April 28
Bryan Mayer -- 3:30 pm in ESB 4133
Fred Hutchinson
Statistical and mathematical modeling of human herpesviruses
Abstract
In this talk, I will discuss applications of statistical and mathematical models to study two different human herpesviruses. First, I will demonstrate how viral load data can be used to estimate viral load thresholds required for transmission of genital herpes infection. This information provides a vital link between viral pathogenesis at the single host level and epidemiologic spread of the virus. Second, using data collected from a study in Uganda, I analyze primary cytomegalovirus (CMV) infections in infants, where little is known about the natural history of infection. In this cohort, infants with primary CMV infection persistently shed virus for extended periods of time (> 180 days) with characteristic kinetics. Here, a mathematical model is employed to explain different phases of primary infection.
May, 2015
Thursday,
May 7
Anmar Khadra -- 3:15 pm in Math 126
Dept of Physiology, MacGill U.
The biophysics of T-cells: From molecular interactions to population dynamics
Abstract
One major scientific challenge in human health is developing effective vaccines to block T-cell responses in spontaneous autoimmune disorders, such as type 1 diabetes (T1D). The ability of these T cells to recognize host cells (e.g., insulin-secreting pancreatic β cells in T1D) and to exert cytotoxicity on self-tissue is dictated by the binding affinity (avidity) of T-cell receptors (TCR) with surface molecules on host cells, called peptide-major histocompatibility complexes (pMHC). Recent findings have shown that in T1D, and other autoimmune disorders, low-avidity autoreactive T cells spontaneously differentiate into memory autoregulatory T-cells that can blunt autoimmunity. These autoregulatory T cells can be selectively expanded using nanovaccines, or nanoparticles (NPs) coated with pMHC, in a PMHC-density- and dose-dependent manner. By using multistep Markov models and continuum avidity model of T cells, one can optimize the efficacy of NPs and identify the causes of abnormalities exhibited by this system. In this talk, we will present our recent work deciphering the kinetics of TCR-interaction with pMHC-coated NPs, and elucidate the role of immunomodulation in altering disease dynamics.

Seminar series sponsored by PIMS.

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