Event type: 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
(Instituto de Ciencias Físicas, UNAM)
Fertilization Regulatory NetworksShow/Hide Abstract
Fertilization is one of the fundamental processes of living systems. Here I will address marine external fertilization and comment on recent work on mammals. I will show experiments that substantiate that sea urchin sperms exhibit chemotaxis as they swim towards the ovum. They are guided by flagellum internal [Ca2+] concentration fluctuations triggered by the binding of chemicals from the oocyte surroundings. Based on experiment, I present a family of logical regulatory networks for the [Ca2+] fluctuation signaling-pathway that reproduce previously observed electrophysiological behaviors and provide predictions, which have been confirmed with new experiments. These studies give insight on the operation of drugs that control sperm navigation. In this systems biology approach, global properties of the [Ca2+] discrete regulatory network dynamics such as
Sep 27, 2019 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
(John Hopkins University)
Water Dynamics in Cells and TissuesShow/Hide Abstract
The mammalian cell surface is highly permeable to water. The cell can also actively control the water flux across the cell surface by pumping solutes (mostly ions), and thereby controlling the cell water content and the cell volume. In this talk, we will explore how the cell also uses active water fluxes to move and change cell shape. The same players in the cell volume control system are involved in driving cell movement, especially in high viscosity environments. Mathematical modeling shows that the water-driven cell movement is energetically costly, but is necessary when the hydraulic environment is viscous. Finally, we will discuss how epithelial cell layers such as the kidney tubule pump water and generate mechanical force.
Oct 25, 2019 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
Control of membrane-bound tethered signaling reactionsShow/Hide Abstract
Many membrane-bound T cell receptors have long, unstructured cytoplasmic tails that contain tyrosine sites. These sites can serve as regulators of receptor activation when phosphorylated or dephosphorylated, while also serving as docking sites for cytosolic enzymes. Interactions between receptors then involve the in-membrane diffusion of the receptor proteins, and reactions between proteins tethered to the receptors’ tails (and hence diffusing within the three-dimensional cytosolic space near the membrane). We develop a particle-based stochastic reaction-diffusion model based on the Convergent Reaction-Diffusion Master Equation to study the combined diffusion of individual receptors within the cell membrane, and chemical reactions between proteins bound to receptor tails. The model suggests a switch-like behavior in the dependence of the fraction of activated receptors on both receptor diffusivity, and on the molecular reach at which two receptor tails can interact. A simplified, analytically solvable model is developed to approximate the more complicated multi-particle system, and used to illustrate how the switch-like behavior arises.
Nov 15, 2019 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
(New York University)
Many-body problem of classical mechanics in cell biologyShow/Hide Abstract
Many-body problem of celestial mechanics revolutionized applied mathematics and continues to provide inspiration. Math/physical communities are much less aware that there are numerous example of fascinating many-body problems of classical mechanics arising in live cells at drastically different scales: instead of years and millions of kilometers, in the cell we deal with minutes and microns. Another big difference is: rather than Newtonian mechanics in empty space, when acceleration is proportional to force, in the cells filled with viscous cytoplasm, we deal with Aristotelian mechanics, in which velocity is proportional to force. Yet another difference is a great diversity of complex inter-body forces in the cell, compared to pleasingly simple gravitational force of celestial mechanics. Because of this diversity, in cell biology we often need to solve the ill-posed inverse problem – reverse-engineering forces from the observed patterns and movements – contrasted with the well-posed direct problem of predicting patterns and movements from known forces. I will discuss two many-body problems of cell biology – assembly of mitotic spindle from two centrosomes and tens of chromosomes, and nuclei positioning in multi-nucleated muscle cells. Three approaches – solutions of ODEs of ‘particle’ models, solutions of PDEs of continuous approximation, and energy minimization, complemented by computer screening – shed light on the molecular origins of the intracellular forces that ensure proper and robust cellular architecture.
Nov 22, 2019 Online Seminar
(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 Utah)
Communicating by touchShow/Hide Abstract
During development, cells figure out their location and fate through morphogen concentration gradients. The most commonly accepted mechanism for morphogen gradient formation is diffusion from a local source combined with degradation. Recently, however, there has been growing experimental evidence for an alternative mechanism, based on the direct delivery of morphogens via thin and long cellular protrusions known as cytonemes. In this talk, we will address the effects of various cytoneme transport mechanisms. We then explore the stochasticity from the discrete nature of transport. To deal with the complex nature of the stochastic process, we introduce the strong Markov property and queuing theory.
Jan 17, 2020 Online Seminar