ICQMB Center Seminar Fall 2024
Tuesday 2:00-3:20 pm PT
Organizers : Mark Alber / Jia Gou
Past Organizers : Qixuan Wang / Weitao Chen / Heyrim Cho / Jia Gou / Mykhailo Potomkin / Yiwei Wang
Tuesday 2:00-3:20 pm PT
Organizers : Mark Alber / Jia Gou
Past Organizers : Qixuan Wang / Weitao Chen / Heyrim Cho / Jia Gou / Mykhailo Potomkin / Yiwei Wang
The format of the seminar is hybrid. One might join the seminars in Skye Hall 268 (unless another location is announced for a specific talk) or online through Zoom. Please contact Dr. Jia Gou (jia.gou@ucr.edu) if you are interested in attending this seminar in the fall quarter.
Fall 2024
Oct 01, 2:00 PM, (Zoom) Organizational Meeting
Oct 08, 2:00 PM, (Zoom) Dr. Sam Walcott (Worcester Polytechnic Institute)
Oct 15, 2:00 PM, (Zoom) Dr. Andreas Buttenschoen (University of Massachusetts Amherst)
Oct 22, 2:00 PM, (Zoom) Dr. Calina Copos (Northeastern University)
Oct 29, 2:00 PM, No seminar
Nov 06, 2:00 PM (Skye 284, jointly with Departmental Colloquium), Dr. Eric Cytrynbaum (University of British Columbia)
Nov 12, 2:00 PM, (Zoom) Dr. Emmanuel Asante-Asamani (Clarkson University)
Nov 19, 2:00 PM, (Zoom) Dr. Magdalena A. Stolarska (University of St. Thomas)
Nov 26, 2:00 PM, (Zoom) Dr. Margaret S. Cheung (Pacific Northwest National Laboratory & University of Washington at Seattle)
Dec 03, 2:00 PM, (Zoom) Dr. Ning Wei (Purdue University)
Upcoming talks:
Dec 03, 2024, 02:00 PM - 03:00 PM Pacific Time
Dr. Ning Wei, Purdue University
Title: The impact of ephaptic coupling and ionic electrodiffusion on arrhythmogenesis in the heart
Abstract: Cardiac myocytes synchronize through electrical signaling to contract heart muscles, facilitated by gap junctions (GJs) in the intercalated disc (ID). GJs provide low-resistance pathways for electrical impulse propagation between myocytes, serving as the primary mechanism for electrical communication in the heart. However, research indicates that conduction can persist without GJs. For instance, GJ knockout mice still exhibit slow, discontinuous electrical propagation, suggesting alternative communication mechanisms. Ephaptic coupling (EpC) serves as an alternative way for cell communication, relying on electrical fields within narrow clefts between neighboring myocytes. Studies show that EpC can enhance conduction velocity (CV) and reduce conduction block (CB), especially when GJs are compromised. Reduced GJs and significant electrochemical gradients are prevalent in various heart diseases. However, existing models often fail to capture their combined influence on cardiac conduction, which limits our understanding of both the physiological and pathological aspects of the heart. Our study aims to address this gap by developing a two-dimensional (2D) multidomain electrodiffusion model that incorporates EpC. This is the first model to capture the dynamics of all ions across multiple domains, enabling us to reveal the impact of EpC in the heart. In particular, we investigated the interplay between ionic electrodiffusion and EpC on action potential propagation, morphology, electrochemical properties and arrhythmogenesis in both healthy and ischemic hearts. Our findings indicate that ionic electrodiffusion enhances CV and reduces CB under strong EpC. Specifically, the electrodiffusion of Ca$^{2+}$ and K$^+$ intensifies the effects of EpC on action potential morphology, whereas Na$^+$ diffusion mitigates these effects. Ionic electrodiffusion also facilitates action potential propagation into ischemic regions when EpC is substantial. Moreover, strong EpC can effectively terminate reentry, prevent its initiation, and lower the maximum dominant frequency (max DF), irrespective of GJ functionality. However, weak EpC may help counteract proarrhythmic effects when GJ coupling is slightly to moderately reduced, contributing to the stabilization of conduction patterns. Additionally, strong EpC notably alters ionic concentrations in the cleft, significantly increasing [K$^+$] and nearly depleting [Ca$^{2+}$], while causing moderate changes in [Na$^+$]. This multidomain electrodiffusion model sheds light on the mechanisms of EpC in the heart.
Previous talks:
Oct 08, 2024, 02:00 PM - 03:00 PM Pacific Time
Dr. Sam Walcott, Worcester Polytechnic Institute
Title: Thick filament activation explains some puzzling aspects of muscle contraction
Abstract: The contraction of muscle cells powers vital processes like locomotion, gastric motility, and blood circulation. The rational development of therapies for dysfunction in these processes, e.g. genetic heart disease, depends on connecting molecular-scale interactions to physiological function. Since the 1950s, the sliding filament and cross bridge theories, as expressed in some relatively simple partial differential equations (PDEs), seemed to relate molecular interactions to the contraction of muscle cells. But, despite the successes of these theories, aspects of muscle contraction, e.g. the history dependence of isometric force, have eluded a mechanistic description. Recently, evidence has emerged of a new molecular mechanism involved in activating the molecules in muscle. In this mechanism, called thick filament activation, molecules in muscle become more active as they collectively generate force.
We added thick filament activation to an integro-PDE model based on the sliding filament and cross bridge theories. We measured force production by muscle cells under conditions where the history dependence of isometric force was evident. We varied unknown parameters in the model to optimize its fit to a subset of our measurements. The model was then able to predict the remaining measurements. Remarkably, the model then also successfully predicted our measurements of the molecular interactions in muscle. This and related work represents progress toward the rational development of therapeutics for muscle dysfunction.
Bio: Dr. Sam Walcott got his undergraduate degree in Biology and his PhD in Theoretical and Applied Mechanics, both from Cornell University. He then did a postdoc at the University of Vermont in Molecular Physiology and Biophysics, performing molecular measurements on muscle proteins. He did a second postdoc at Johns Hopkins University in Mechanical Engineering. He joined the Department of Mathematics at UC Davis in 2011 and then moved to the Mathematical Sciences Department at WPI in 2019.
Oct 15, 2024, 02:00 PM - 03:00 PM Pacific Time
Dr. Andreas Buttenschoen, University of Massachusetts Amherst
Title: How cells stay together; a mechanism for maintenance of a robust cluster explored by local and nonlocal continuum models
Abstract: Formation of organs and specialized tissues in embryonic development requires migration of cells to specific targets. In some instances, such cells migrate as a robust cluster. We here explore a recent local approximation of nonlocal continuum models by Falcó, Baker, and Carrillo (2023). We apply their theoretical results by specifying biologically-based cell-cell interactions, showing how such cell communication results in an effective attraction-repulsion Morse potential. We then explore the clustering instability, the existence and size of the cluster, and its stability. We also extend their work by investigating the accuracy of the local approximation relative to the full nonlocal model.
Bio: Dr. Buttenschoen is an Assistant Professor at the University of Massachusetts Amherst, specializing in applied mathematics with a focus on mathematical biology. He holds a Ph.D. in Applied Mathematics from the University of Alberta (2018).
As an applied mathematician, Andreas bridges mathematical, computational, and biological sciences, focusing on collective cell behaviors. His research employs differential equations and cell-based computational models, to study phenomena like wound healing, embryogenesis, and cancer metastasis. Utilizing expertise in dynamical systems, bifurcation theory, and group theory, he aims to uncover universal principles governing biological tissue formation and behavior.
Prior to his current position, he held an NSERC Post-doctoral Fellowship at the University of British Columbia (2018-2022) and completed a MITACS internship at INRIA-Paris.
Oct 22, 2024, 02:00 PM - 03:00 PM Pacific Time
Dr. Calina Copos, Northeastern University
Title: The tug-of-war at cell-cell junctions: coordination of symmetry breaking events
Abstract: Symmetry breaking is a ubiquitous process in biological cells. At the onset of migration, stationary cells must undergo a drastic intracellular reorganization to acquire the migratory phenotype with a front-to-back polarity due to asymmetric distribution of proteins, lipids, and other molecules. Symmetry breaking has been studied theoretically extensively as an example of pattern formation, but much less is known about how symmetry breaking is coordinated, communicated, and synchronized across cell groups. Just as charge dipoles align in an external electric field, the question we ask here is how does a pair of cells `communicate' in order to ensure co-oriented front-to-rear axes?
In a combined structural-chemical model for cell polarity, we find that synchronized pattern formation is established through a tug-of-war at the cell-cell junction, resolved either directly mechanically or biochemically, through asymmetric regulation of signaling molecules. The same interactions lead to supracellular (i.e. leader-follower) organization as well. We also contextualize our findings within a larger effort to understand the intercellular interactions for collective behavior.
Bio: Dr. Calina Copos is an Assistant Professor of Mathematics and Biology at Northeastern University. Her research group is broadly interested in mathematical biology and numerical and computational methods for PDEs, with a particular focus on the cell cytoskeleton and cell migration in tissue development, homeostasis, and regeneration. Prof. Copos received her Ph.D. in Applied Mathematics at University of California, Davis and did her postdoctoral work at the Courant Institute at New York University.
Nov 06, 2024, 04:00 PM - 05:00 PM Pacific Time
Dr. Eric Cytrynbaum, University of British Columbia
Title: Mathematical models of spatiotemporal organization in multicellular organisms
Abstract: In this talk, I’ll discuss two recent lines of research in my group, related by the common element of being a multiscale problem of spatial organization.
(1) For over a century, the development and replacement of reptile teeth has been of interest in comparative anatomy and evolutionary biology due to the prevalence of teeth in the fossil record and, more recently, for understanding spatiotemporal patterning in developmental biology as well as the fundamentals of tooth replacement for a clinical context. In collaboration with the Richman Lab (UBC Dentistry), we are using the Leopard Gecko as a model organism to understand the mechanisms underlying the regular and long-lasting spatiotemporal patterns of tooth replacement seen in many polyphyodonts. I will describe the data and our implementation and analysis of several mechanisms that have been proposed in the past to explain the observations. Finding shortcomings in these models, we propose a new model, the Phase Inhibition Model, a coupled phase oscillator model, which does better at explaining the data.
(2) Many externally bilaterally-symmetric animals, including both vertebrates and invertebrates, have an internal left-right asymmetry that is established during embryo development. This asymmetry can be critical for proper organ function (e.g. the mammalian heart). In C. elegans, left-right asymmetry (chirality) arises during cell division at the four-cell stage and eventually manifests in a consistent handedness in the twisting of intestine and gonad in the adult. In collaboration with the Sugioka Lab (UBC Zoology), we are developing models to explain the onset of chirality. Chirality appears intracellularly during cell division in the form of chiral flow of the actomysosin cortex. We hypothesize that this flow induces friction forces between neighbouring cells mediated by adhesions. The model takes the form of force balance differential equations and does well in comparison with quantitative data extracted from live-cell and in vitro imaging.
Nov 12, 2024, 02:00 PM - 03:00 PM Pacific Time
Dr. Emmanuel Asante-Asamani, Clarkson University
Title: A multiscale modeling framework for uncovering the mechanisms driving long range cell-cell signaling during tissue patterning
Abstract: The spatiotemporal distribution of morphogens is important for proper development of biological tissue patterns. One means of distribution is via cytonemes (signaling filopodia), which are long actin protrusions that can grow to be several cell diameters long. In the fruit fly, Drosophila melanogaster, cytonemes have been implicated in the regulation of Notch-Delta signaling, which is the primary mechanism governing the spatial organization of sensory bristles on the fly dorsal thorax. Whereas experimental and computational simulations suggest that the length dynamics of cytonemes regulate the density of sensory bristles, the precise mechanism by which signaling receptors are activated and signaling molecules transported along cytonemes is unknown. In collaboration with a developmental biologist at Howard University, my lab is developing a multiscale modeling framework to elucidate the activation and transport mechanisms that drive long-range signaling during bristle patterning. In this talk, I will describe our data-driven approach to creating and validating these models at the cellular, molecular and tissue scales.
Bio: Dr. Asante-Asamani is an Assistant Professor of Mathematics at Clarkson University in Potsdam, New York. His research group is focused on the development, analysis, and numerical simulation of multiscale models of cell migration and tissue patterning as well as the application of machine learning methods to quantify biological patterns. He received his PhD in Applied Mathematics at the University of Wisconsin-Milwaukee in 2016 and was a postdoctoral
researcher at the Hunter College campus of the City University of New York, where he developed mathematical models to understand how eukaryotic cells migrate under confinement using pressure-driven membrane protrusions.
Nov 19, 2024, 02:00 PM - 03:00 PM Pacific Time
Dr. Magdalena A. Stolarska, University of St. Thomas
Title: Active membrane dynamics and its effect of cell motility: computational studies
Abstract: Cell motility is essential in many biological phenomena, and it involves highly coordinated integration of several process within a cell, including cytoskeletal remodeling, the formation and degradation of adhesions, fluid flow into and out of the cell, deformations of the cell membrane, and interaction with the extracellular matrix. In this talk, I will present mathematical models that aim to investigate how the integration of these processes leads to cell movement. I first present earlier work of a two-dimensional model and finite element simulations that investigate how substrate stiffness controls the placement and size of focal adhesions, which in turn regulate downstream processes involved in motility. In the second part of the talk, I discuss a variation of the first model, in which we consider active deformation of the lipid bilayer and its effect on cell movement. Active deformations of the membrane have generally been overlooked in mathematical models. However, it has been established experimentally that membrane dynamics, including unfolding and exocytosis from intracellular reservoirs to the lipid bilayer, is necessary for the large changes in cell shape that occur during cell spreading and other types of motility. By using the finite element method to simulate cell spreading in an axisymmetric geometry, we show that the membrane plays a critical role in controlling focal adhesions and in modulating protrusive activity and actin retrograde flow, the balance of which allows for large spread areas and regulates sensitivity of cell spread areas to substrate mechanical properties. A broad goal of the work presented will be to illustrate the importance of a systems-level modeling approach in understanding the many processes involved in cell movement.
Bio: Dr. Magda Stolarska is a Professor of Mathematics at the University of St. Thomas is St. Paul, MN, where she has been since 2006. Her research focuses on using principles of continuum mechanics in modeling mechanical aspects of cell movement and tissue growth. She received her Ph.D. in Engineering Sciences and Applied Mathematics from Northwestern University, where she studied computational methods for fracture. As a postdoctoral researcher at the University of Minnesota, Magda began applying her training in mechanics to biological processes.
Nov 26, 2024, 02:00 PM - 03:00 PM Pacific Time
Dr. Margaret S. Cheung,
Pacific Northwest National Laboratory-Seattle and University of Washington, Seattle
Title: NW-BRaVE for Biopreparedness:
Enhancing biopreparedness through a model system to understand the molecular mechanisms that lead to pathogenesis and disease transmission
Abstract: In my presentation, I will provide a current update on a recently awarded project, NW-BRaVE, by the Department of Energy Office of Science in response to the National Biopreparedness Initiative. The science of biopreparedness to counter biological threats hinges on understanding the fundamental principles and molecular mechanisms that lead to pathogenesis and disease transmission. NW-BRaVE’s vision to address this challenge is to create a powerful and user-friendly platform to elucidate the fundamental principles of how molecular interactions drive pathogen-host relationships and host shifts. We will enable groundbreaking discoveries by integrating a wide range of structural, genomics, proteomics, and other advanced omics measurements, along with evolutionary and artificial intelligence predictions. To make sure the system is applicable to real-world problems, it will be developed in the context of a tractable model system, the small, abundant, and accessible photosynthetic cyanobacteria and their constantly co-adapting viral pathogens, cyanophages. This model will maintain the system’s applicability to real-world problems and techniques, but the overall focus will be on elucidating general principles of detecting, assessing, and surveilling molecular interaction, adaptation, and coevolution that are system agnostic and therefore extensible to any other viral-host interaction. The impact of the project will be to develop, implement, and test a platform to assess host-pathogen molecular interactions, adaptation to hosts and host shifts, and coevolution between hosts and pathogens. This ability will be critical for designing early interventions to address future threats.
Bio: Dr. Margaret S. Cheung graduated from the National Taiwan University in 1994 and went on to obtain a Ph.D. degree from the University of California at San Diego in 2003. Cheung was then awarded a Sloan Postdoctoral Research Fellowship to work at the University of Maryland. In 2006, Cheung started her laboratory at the University of Houston and was later named Moores Professor of Physics. She was Senior Scientist and Outreach Director of the Center for Theoretical Biological Physics from Rice University. Since 2021, she has moved to the Environmental Molecular Science Laboratory/Pacific Northwest National Laboratory (PNNL) as Physicist with a joint appointment from the University of Washington, Seattle as Faculty Fellow of Physics. Utilizing AI/ML techniques and data-driven models, she leads a team of scientists at PNNL in developing a digital twin of microbial systems, aimed at addressing tough national challenges in Biopreparedness. She enjoys spending time with her family, traveling, and gardening. She is also a Kraken hockey fan.