Event category: Fall 2020
(University of California, Irvine)
Multiscale inference and modeling of cell fate via single-cell dataShow/Hide Abstract
Cells make fate decisions in response to dynamic environmental and pathological stimuli as well as cell-to-cell communications. Recent technological breakthroughs have enabled to gather data in previously unthinkable quantities at single cell level, starting to suggest that cell fate decision is much more complex, dynamic, and stochastic than previously recognized. Multiscale interactions, sometimes through cell-cell communications, play a critical role in cell decision-making. Dissecting cellular dynamics emerging from molecular and genomic scale in single-cell demands novel computational tools and multiscale models. In this talk, through multiple biological examples we will present our recent effort to use single-cell RNA-seq data and spatial imaging data to uncover new insights in development, regeneration, and cancers. We will also present several new computational tools and mathematical modeling methods that are required to study the complex and dynamic cell fate process through the lens of single cells. Zoom
Nov 24, 2020 Online Seminar
(University of British Columbia)
From Cell polarity to intracellular networks in single and collective cell motilityShow/Hide Abstract
Cell migration plays a central role in embryonic development, wound healing and immune surveillance. In 2008, Yoichiro Mori, Alexandra Jilkine and I published a model for the initial step of cell migration, the front-back chemical polarization that sets a cell’s directionality. (More detailed mathematical properties of this model were described by the same group in 2011.) Since then, progress has been made in investigating how that simple “wave-pinning" mechanism is shaped and tuned by feedback from other proteins, such as actin, from the cell’s environment (extracellular matrix), from interplay with larger signaling networks, and from cell-cell interactions. In this talk I will describe some of this progress, with emphasis on links to experiments on melanoma cell motility. If time permits, I will also briefly describe more recent work on collective cell migration that we are currently undertaking.
Sep 22, 2020 Online Seminar
Opinion Dynamics with Tunable SensitivityShow/Hide Abstract
I will present a general model of continuous-time opinion dynamics for an arbitrary number of agents that sense or communicate over a network and form real-valued opinions about an arbitrary number of options. Drawing from biology, physics, and social psychology, an attention parameter is introduced to modulate social influence and a saturation function to bound inter-agent and intra-agent opinion exchanges. This yields simply parameterized dynamics that exhibit the range of opinion formation behaviors predicted by model-independent bifurcation theory but not exhibited by linear models or existing nonlinear models. Behaviors include rapid and reliable formation of multistable consensus and dissensus states, even in homogeneous networks, as well as ultra-sensitivity to inputs, robustness to uncertainty, flexible transitions between consensus and dissensus, and opinion cascades. Augmenting the opinion dynamics with feedback dynamics for the attention parameter results in tunable thresholds that govern sensitivity and robustness. The model provides new means for systematic study of dynamics on natural and engineered networks, from information spread and political polarization to collective decision making and dynamic task allocation. This is joint work with Alessio Franci (UNAM, Mexico) and Anastasia Bizyaeva (Princeton). The talk is based on version 2 of the paper “A General Model of Opinion Dynamics with Tunable Sensitivity”, which will be available on Tuesday October 13, 2020 here: https://arxiv.org/abs/2009.04332v2
Oct 13, 2020 Online Seminar
(University of Washington)
Constraints on the dimensionality of neural representationsShow/Hide Abstract
In the domain of computational/theoretical neuroscience a recently revived question is about the complexity of neural data. This question can be tackled by studying the dimensionality of such data: is neural activity high or low dimensional? How does the geometrical structure of neural activity depend on behavior, learning or the underlying connectivity? In my talk I will show how it is possible to link these three aspects (animal behavior, learning and underlying network connectivity) to the geometrical properties of neural data, with an emphasis on dimensionality phenomena. My results depart from neural recordings and aim at building understanding of neural dynamics by means of theoretical and computational tools. Such tools are mainly borrowed from the domain of neural networks dynamics, using a blend of large scale dynamical systems and statistical physics approaches.
Oct 20, 2020 Online Seminar
Modeling and measuring pattern formation in zebucturesShow/Hide Abstract
Wild-type zebrafish (Danio rerio) are characterized by black and yellow stripes, which form on their body and fins due to the self-organization of thousands of pigment cells. Mutant zebrafish and sibling species in the Danio genus, on the other hand, feature altered, variable patterns, including spots and labyrinth curves. The longterm goal of my work is to better link genotype, cell behavior, and phenotype by helping to identify the specific alterations to cell interactions that lead to these different fish patterns. Using a phenomenological approach, we develop agent-based models to describe the behavior of individual cells and simulate pattern formation on growing domains. In this talk, I will overview our models and highlight how topological techniques can be used to quantitatively compare our simulations with in vivo images. I will also discuss future directions related to taking a more mechanistic approach to modeling cell behavior in zebrafish.
Oct 27, 2020 Online Seminar
(Ohio State University)
Antagonistic motor protein dynamics in contractile ring structuresShow/Hide Abstract
Ring-shaped contractile structures play important roles in biological processes including wound healing and cell division. Many of these contractile structures rely on motor proteins called myosins for constriction. We investigate force generation by the Type II myosins NMY-1 and NMY-2 in ring channels, contractile structures in developing oocytes of the nematode worm C. elegans, as our model system. By exploiting the ring channel’s circular geometry, we derive a second order ODE to describe the evolution of the radius of the ring channel. By comparing our model predictions to experimental depletion of NMY-1 and NMY-2, we show that these myosins act antagonistically to each other, with NMY-1 exerting force orthogonally and NMY-2 exerting force tangentially to the ring channel opening. Stochastic simulations are currently being used to determine how NMY-1 and NMY-2 may be producing these antagonistic forces, with new tools from topological data analysis identifying persistent ring-like structures in the simulation data.
Nov 3, 2020 Online Seminar
(University of Minnesota)
Understanding the role of phenotypic switching in cancer drug resistanceShow/Hide Abstract
Recent findings suggest that cancer cells can acquire transient resistant phenotypes via epigenetic modifications and other non-genetic mechanisms. Although these resistant phenotypes are eventually relinquished by individual cells, they can temporarily ’save’ the tumor from extinction and enable the emergence of more permanent resistance mechanisms. These observations have generated interest in the potential of epigenetic therapies for long-term tumor control or eradication. In this talk, I will discuss some mathematical models for exploring how phenotypic switching at the single-cell level affects resistance evolution in cancer. As an example, we will explore the role of MGMT promoter methylation in driving resistance to temozolomide in glioblastoma.
Nov 10, 2020 Online Seminar
(University of Alberta)
Population Dynamics in Changing EnvironmentsShow/Hide Abstract
Classical population dynamics problems assume constant unchanging environments. However, realistic environments fluctuate in both space and time. My lecture will focus on the analysis of population dynamics in environments that shift spatially, due either to advective flow (eg., river population dynamics) or to changing environmental conditions (eg., climate change). The emphasis will be on the analysis of nonlinear advection-diffusion-reaction equations and related models in the case where there is strong advection and environments are heterogeneous. I will use methods of spreading speed analysis, net reproductive rate and inside dynamics to understand qualitative outcomes. Applications will be made to river populations and to the genetic structure of populations subject to climate change.
Nov 17, 2020 Online Seminar