BEGIN:VCALENDAR VERSION:2.0 PRODID:researchseminars.org CALSCALE:GREGORIAN X-WR-CALNAME:researchseminars.org BEGIN:VEVENT SUMMARY:Bill Bement (U Wisconsin Madison) DTSTART:20211018T150000Z DTEND:20211018T154000Z DTSTAMP:20260404T041840Z UID:BIRS-21w5154/1 DESCRIPTION:Title: A versatile cytokinetic circuit based on Rho\, F-actin\, Ect2 and RGA34\nby Bill Bement (U Wisconsin Madison) as part of BIRS worksh op Mathematics of the Cell: Integrating Signaling\, Transport and Mechanic s\n\n\nAbstract\nCytokinesis in animal cells is dependent on the concentra tion of active Rho (Rho-GTP or Rho-T) at the equatorial cell cortex\, wher e it directs formation of the F-actin (filamentous actin) and myosin-2-ric h cytokinetic apparatus. Immediately prior to and during cytokinesis\, th e cortex behaves as an excitable medium\, generating propagating waves of Rho activity and F-actin assembly which become concentrated and amplified at the equatorial cortex by the action of the mitotic spindle. Excitable dynamics implies the existence of a circuit based on positive feedback cou pled to delayed negative feedback. Previous work indicated that positive feedback during cytokinesis is based on Rho-T and Ect2 (a Rho activator)\, while negative feedback is somehow dependent on F-actin. Here we show th at the delayed feedback is based on the GAP (Rho inactivator) RGA34: RGA3 4 localizes to waves that are concentrated and amplified at the equatorial cortex\; RGA34 waves "chase" (follow) Rho-T waves\; RGA34 colocalizes wit h F-actin\; experimental disruption or modulation of cortical F-actin resu lts in corresponding disruption or modulation of RGA34 distribution\; and\ , most compellingly\, coexpression of RGA34 and Ect2 in cells that are not normally excitable is sufficient to induce high amplitude waves of Rho-T and F-actin that pervade the entire cortex. Variation of the ratio of RGA 34 to Ect2 produces quantitative and qualitative changes in cortical dynam ics\, with low ratios producing pulsed contractions and high ratios produc ing overtly psychedelic waves. We conclude that Rho\, F-actin\, Ect2 and RGA34 form the core of a versatile cortical excitability circuit that regu lates diverse cortical behaviors.\n LOCATION:https://stable.researchseminars.org/talk/BIRS-21w5154/1/ END:VEVENT BEGIN:VEVENT SUMMARY:Andreas Buttenschoen (University of British Columbia) DTSTART:20211018T154000Z DTEND:20211018T162000Z DTSTAMP:20260404T041840Z UID:BIRS-21w5154/2 DESCRIPTION:Title: Spatio-temporal heterogeneities in a mechano-chemical model of collective cell migration\nby Andreas Buttenschoen (University of Bri tish Columbia) as part of BIRS workshop Mathematics of the Cell: Integrati ng Signaling\, Transport and Mechanics\n\n\nAbstract\nAbstract: Small GTPa ses\, such as Rac and Rho\, are well known central regulators of cell morp hology and motility\, whose dynamics also play a role in coordinating coll ective cell migration. Experiments have shown GTPase dynamics to be affect ed by both chemical and mechanical cues\, but also to be spatially and tem porally heterogeneous. This heterogeneity is found both within a single ce ll\, and between cells in a tissue. For example\, sometimes the leader and follower cells display an inverted GTPase configuration. While progress o n understanding GTPase dynamics in single cells has been made\, a major re maining challenge is to understand the role of GTPase heterogeneity in col lective cell migration. Motivated by recent one-dimensional experiments (e .g. micro-channels) we introduce a one-dimensional modelling framework all owing us to integrate cell bio-mechanics\, changes in cell size\, and deta iled intra-cellular signalling circuits (reaction-diffusion equations). Us ing this framework\, we build cell migration models of both loose (mesench ymal) and cohering (epithelial) tissues. We use numerical simulations\, an d analysis tools\, such as bifurcation analysis\, to provide insights into the regulatory mechanisms coordinating collective cell migration. We show how local perturbations to GTPase signalling due to cell-cell interaction s or tension lead to a variety of dynamics\, resembling the behavior of sm all cell groups.\n LOCATION:https://stable.researchseminars.org/talk/BIRS-21w5154/2/ END:VEVENT BEGIN:VEVENT SUMMARY:Garegin Papoian (University of Maryland) DTSTART:20211018T164000Z DTEND:20211018T172000Z DTSTAMP:20260404T041840Z UID:BIRS-21w5154/3 DESCRIPTION:Title: Simulating Deformable Vesicles Containing Complex Cytoskeletal Networks\nby Garegin Papoian (University of Maryland) as part of BIRS workshop Mathematics of the Cell: Integrating Signaling\, Transport and M echanics\n\nAbstract: TBA\n LOCATION:https://stable.researchseminars.org/talk/BIRS-21w5154/3/ END:VEVENT BEGIN:VEVENT SUMMARY:Ajay Gopinathan (University of California\, Merced) DTSTART:20211018T172000Z DTEND:20211018T180000Z DTSTAMP:20260404T041840Z UID:BIRS-21w5154/4 DESCRIPTION:Title: From geometric incompatibility to function: Curvature sensing with twisted filaments\nby Ajay Gopinathan (University of California\, Merced) as part of BIRS workshop Mathematics of the Cell: Integrating Sig naling\, Transport and Mechanics\n\n\nAbstract\nFilamentous biopolymers ar e involved in a variety of critical cellular processes including facilitat ing intracellular transport\, segregating genetic material and force produ ction during motility and cell division. In this talk\, I will discuss how geometrical incompatibility\, such as size or curvature mismatches\, betw een the biopolymer structure and its environment can be translated into fu nction. As a particular example\, I will describe how the frustrated inter play between the helicity of protein filaments\, their elasticity and thei r interactions with curved surfaces can lead to novel conformational state s with functional implications. Our work shows that biopolymers are inhere ntly very sensitive to this coupling\, allowing twisted filaments to sense curvature at length scales much larger than themselves. Such a coupling c ould be exploited for the regulation of a variety of processes such as the targeted exertion of forces\, signaling\, and self-assembly in response t o geometric cues including the local mean and Gaussian curvatures. I will discuss recent in vivo experiments to validate our predictions and conclud e with some of our latest work extending our formalism as well as future p rospects.\n LOCATION:https://stable.researchseminars.org/talk/BIRS-21w5154/4/ END:VEVENT BEGIN:VEVENT SUMMARY:Ed Munro (University of Chicago) DTSTART:20211018T202000Z DTEND:20211018T210000Z DTSTAMP:20260404T041840Z UID:BIRS-21w5154/5 DESCRIPTION:Title: Structural memory of filament alignment during contractile rin g assembly in C. elegans embryos\nby Ed Munro (University of Chicago) as part of BIRS workshop Mathematics of the Cell: Integrating Signaling\, Transport and Mechanics\n\n\nAbstract\nDuring cytokinesis in animal cells\ , signals from the mitotic apparatus position an equatorial zone of RhoA activity which drives local assembly of actin filaments and bipolar myosin II minifilaments. These in turn reorganize to form a circumferentially a rray of filaments that constricts to drive cell division. But how cells ra pidly build and maintain this alignment in the face of continuous turnover of filaments and motors has remained somewhat mysterious. I will describe our recent efforts to resolve this mystery through a combination of high speed TIRF microscopy\, single molecule imaging\, particle tracking analys is and computational modeling. We have found that locally compressive flo ws\, driven by myosin II\, reorient filaments to build alignment. However\ , single filaments turn over far too fast for reorientation of single fila ments to do this job. Instead\, we find that long filaments assembled by f ormins use existing filaments as templates to orient their growth. We refe r to this process as filament guided filament assembly (FGFA). We show th at FGFA endows small filament bundles within the cortex with a structural memory of filament orientation\; by tuning the strength of FGFA\, the dura tion of this memory can be made arbitrarily long relative to the lifetimes of individual filaments. In particular\, we show that FGFA is sufficientl y strong to explain the rapid emergence and stable persistence of orientat ion in the C. elegans contractile ring. I will also discuss the implicatio ns of these findings for the maintenance of cortical actin network archite cture and the microscopic origins of self-organized contractility.\n LOCATION:https://stable.researchseminars.org/talk/BIRS-21w5154/5/ END:VEVENT BEGIN:VEVENT SUMMARY:Orion Weiner (University of California San Francisco)) DTSTART:20211018T210000Z DTEND:20211018T214000Z DTSTAMP:20260404T041840Z UID:BIRS-21w5154/6 DESCRIPTION:Title: Self-organization of actin regulators guides cell morphogenesi s\nby Orion Weiner (University of California San Francisco)) as part o f BIRS workshop Mathematics of the Cell: Integrating Signaling\, Transport and Mechanics\n\n\nAbstract\nTo control their shape and movement\, cells leverage nucleation promoting factors (NPFs) to regulate when and where th ey polymerize actin. Despite having similar upstream activators and downs tream effectors\, different NPFs organize dramatically different membrane deformations ranging from finger-like filopodia to sheet-like lamellipodia to endocytic membrane invaginations. We seek to understand the local ru les that underlie these disparate morphological programs. We have uncove red different patterns of protein oligomerization and geometry-sensing tha t regulate two important regulators of cell movement. The WAVE complex ol igomerizes into a saddle-sensing linear template that could explain expand ing self-straightening lamellipodia. In contrast\, the homologous NPF WASP repurposes an arrested endocytic-like program to connect substrate topolo gy to cell polarity. Our work suggests how feedback between cell shape an d actin regulators instructs cell morphogenesis.\n LOCATION:https://stable.researchseminars.org/talk/BIRS-21w5154/6/ END:VEVENT BEGIN:VEVENT SUMMARY:Adriana Dawes (he Ohio State University) DTSTART:20211018T220000Z DTEND:20211018T224000Z DTSTAMP:20260404T041840Z UID:BIRS-21w5154/7 DESCRIPTION:Title: Dynein localization and pronuclear movement in the early C. el egans embryo\nby Adriana Dawes (he Ohio State University) as part of B IRS workshop Mathematics of the Cell: Integrating Signaling\, Transport an d Mechanics\n\n\nAbstract\nAsymmetric cell division\, where daughter cells inherit unequal amounts of specific factors\, is critical for development and cell fate specification. In polarized cells\, where specific factors are segregated to opposite ends of the cell\, asymmetric cell division occ urs as a result of dynein-mediated centrosome positioning along the polari ty axis. Early embryos of the nematode worm C. elegans polarize in respons e to fertilization\, and rely on proper centrosome positioning for cell fa te specification and development. Depletion of certain proteins results in defective movement of centrosomes and the associated pronuclear complex i n the early embryo. We developed a novel measure to characterize the oscil latory nature of these movement defects\, and demonstrated that dynein loc alization is not impaired in the presence of wobble. Stochastic and contin uum modeling of the centrosome and pronuclear complex movement is being us ed to identify possible mechanisms responsible for the impaired movement.\ n LOCATION:https://stable.researchseminars.org/talk/BIRS-21w5154/7/ END:VEVENT BEGIN:VEVENT SUMMARY:Stéphanie Portet (University of Manitoba) DTSTART:20211018T224000Z DTEND:20211018T232000Z DTSTAMP:20260404T041840Z UID:BIRS-21w5154/8 DESCRIPTION:Title: Transport of intermediate filaments in cells\nby Stéphani e Portet (University of Manitoba) as part of BIRS workshop Mathematics of the Cell: Integrating Signaling\, Transport and Mechanics\n\n\nAbstract\nT ogether with actin and microtubules\, intermediate filaments (IFs) are ess ential components of the cytoskeleton. IF proteins self-assemble into long elastic filaments organized in networks. Intracellular transport of IFs i s essential for the dynamic rearrangements of the network and is regulated by intracellular signals. Network dynamics and organization regulate IF c ellular functions.\nIn collaboration with experimentalists\, we have been working on deciphering the features of the intracellular transport of IFs that results from the interplay between actin-dependent retrograde flow\, and anterograde and retrograde microtubule-dependent transports driven by processive motors kinesin-1 and dynein. I will present an overview of mode ls and data we have been developing for a few years.\n LOCATION:https://stable.researchseminars.org/talk/BIRS-21w5154/8/ END:VEVENT BEGIN:VEVENT SUMMARY:Thomas Fai (Brandeis University) DTSTART:20211019T154000Z DTEND:20211019T162000Z DTSTAMP:20260404T041840Z UID:BIRS-21w5154/10 DESCRIPTION:Title: Coarse-grained stochastic model of myosin-driven vesicles int o dendritic spines\nby Thomas Fai (Brandeis University) as part of BIR S workshop Mathematics of the Cell: Integrating Signaling\, Transport and Mechanics\n\n\nAbstract\nWe model vesicle transport into dendritic spines\ , which are micron-sized structures located at the postsynapses of neurons characterized by their thin necks and bulbous heads. Recent high-resoluti on 3D images show that spine morphologies are highly diverse. To study the influence of geometry on transport\, our model reduces the fluid dynamics of vesicle motion to two essential parameters representing the system geo metry and elasticity. Upon including competing molecular motor species tha t push and pull on vesicles\, the model exhibits multiple steady states th at neurons could exploit in order to control the strength of synapses. Mor eover\, the small numbers of motors lead to random switching between these steady states. We describe a method that incorporates stochasticity into the model to predict the probability and mean time of translocation as a f unction of spine geometry.\n LOCATION:https://stable.researchseminars.org/talk/BIRS-21w5154/10/ END:VEVENT BEGIN:VEVENT SUMMARY:Paul Bressloff (University of Utah) DTSTART:20211019T164000Z DTEND:20211019T172000Z DTSTAMP:20260404T041840Z UID:BIRS-21w5154/11 DESCRIPTION:Title: Biological pattern formation: beyond classical diffusion-base d morphogenesis\nby Paul Bressloff (University of Utah) as part of BIR S workshop Mathematics of the Cell: Integrating Signaling\, Transport and Mechanics\n\n\nAbstract\nA fundamental question in modern cell biology is how cellular and subcellular structures are formed and maintained given th eir particular molecular components. How are the different shapes\, sizes\ , and functions of cellular organelles determined\, and why are specific s tructures formed at particular locations and stages of the life cycle of a cell? In order to address these questions\, it is necessary to consider t he theory of self-organizing non-equilibrium systems. We are particularly interested in identifying and analyzing novel mechanisms for pattern forma tion that go beyond the standard Turing mechanism and diffusion-based mech anisms of protein gradient formation. In this talk we present three exampl es of non-classical biological pattern formation: (i) Transport models of cytoneme-based morphogenesis. (ii) Space-dependent switching diffusivities and cytoplasmic protein gradients in the C. elegans zygote (iii) Hybrid T uring mechanism for the homeostatic control of synaptogenesis in C. elegan s.\n LOCATION:https://stable.researchseminars.org/talk/BIRS-21w5154/11/ END:VEVENT BEGIN:VEVENT SUMMARY:Alexandria Volkening (Purdue University) DTSTART:20211019T172000Z DTEND:20211019T180000Z DTSTAMP:20260404T041840Z UID:BIRS-21w5154/12 DESCRIPTION:Title: Modeling and topological data analysis of zebrafish patterns< /a>\nby Alexandria Volkening (Purdue University) as part of BIRS workshop Mathematics of the Cell: Integrating Signaling\, Transport and Mechanics\n \n\nAbstract\nWild-type zebrafish are small fish named for their dark and light stripes\, but mutant zebrafish feature variable skin patterns\, incl uding spots and labyrinth curves. All of these patterns form as the fish g row due to the interactions of tens of thousands of pigment cells in the s kin. This leads to the question: how do cell interactions change to create mutant patterns? The longterm motivation for my work is to help shed ligh t on this question and better link genes\, cell behavior\, and visible ani mal characteristics. Toward this goal\, I develop agent-based and continuu m models to describe cell behavior in growing 2D domains. However\, my age nt-based models are stochastic and have many parameters\, and comparing si mulated patterns and fish images is often a qualitative process. In this t alk\, I will overview our models and discuss how methods from topological data analysis can be used to quantitatively describe cell-based patterns a nd compare in vivo and in silico images.\n LOCATION:https://stable.researchseminars.org/talk/BIRS-21w5154/12/ END:VEVENT BEGIN:VEVENT SUMMARY:Padmini Rangamani (UCSD) DTSTART:20211019T193000Z DTEND:20211019T201000Z DTSTAMP:20260404T041840Z UID:BIRS-21w5154/13 DESCRIPTION:Title: Elucidating the role of membrane tension in cellular processe s using continuum modeling\nby Padmini Rangamani (UCSD) as part of BIR S workshop Mathematics of the Cell: Integrating Signaling\, Transport and Mechanics\n\n\nAbstract\nMembrane tension plays a critical role in many ce llular processes. Experiments using both cellular and reconstituted system s have shown that tension plays a critical role in membrane-protein intera ctions for curvature generation. Cellular membranes can be thought of as e lastic lipid bilayers that contain a variety of proteins\, including ion c hannels\, receptors and scaffolding proteins. These proteins are known to diffuse and aggregate in the plane of the membrane and to influence the be nding of the membrane. Experiments have shown that lipid flow in the plane of the membrane is closely coupled with the diffusion and aggregation of proteins. Thus\, there is a need for a comprehensive framework that accoun ts for the interplay between these processes. In this talk\, I will discus s some recent theoretical and computational developments from my group usi ng continuum modeling that allows for better comparison of membrane deform ations with experiments. Our primary focus will be membrane trafficking\, particularly endocytosis but the theoretical developments are broadly appl icable to many membrane curvature generating processes.\n\n\nWe formulate the free energy of the membrane with a Helfrich-like curvature elastic ene rgy density function modified to account for the chemical potential energy of the proteins. We derive the conservation laws and equations of motion for this system. Finally\, we present results from dimensional analysis an d numerical simulations and demonstrate the effect of coupled transport pr ocesses in governing the dynamics of membrane bending\, protein aggregatio n\, and diffusion. We find that feedback between curvature and aggregation results in domains that result in membrane microdomains. This work is in collaboration with David Saintillan (UCSD\, MAE).\n LOCATION:https://stable.researchseminars.org/talk/BIRS-21w5154/13/ END:VEVENT BEGIN:VEVENT SUMMARY:Wouter-Jan Rappel (University of California\, San Diego) DTSTART:20211019T201000Z DTEND:20211019T205000Z DTSTAMP:20260404T041840Z UID:BIRS-21w5154/14 DESCRIPTION:Title: Combining experiments and modeling to better understand chemo taxis\nby Wouter-Jan Rappel (University of California\, San Diego) as part of BIRS workshop Mathematics of the Cell: Integrating Signaling\, Tra nsport and Mechanics\n\n\nAbstract\nMany motile eukaryotic cells can respo nd to external chemical gradients\, \nresulting in direct motion. During t his motion\, cells can use and switch between \ndifferent modes of migrati on. To better understand these different modes\, \nwe combine experiments\ , that use traction force and fluorescent microscopy\, \nand mod eling. Specifically\, we quantitatively determine the distribution of \nof actin and myosin and correlate these with traction force patterns in euka ryotic cells \nthat move and switch between keratocyte-like fan-shaped\, o scillatory\, \nand amoeboid modes. We find that the wave dynamics of the c ytoskeletal components \ncritically determine the traction force pattern\, cell morphology\, and migration mode. \nFurthermore\, we find that fan-sh aped cells can exhibit two different propulsion \nmechanisms\, each with a distinct traction force pattern. Finally\, we show that \nthe traction fo rce patterns can be recapitulated using the computational model\, \nwhich uses the experimentally determined spatio-temporal distributions of actin \nand myosin forces and a viscous cytoskeletal network. Our results sugges t that \ncell motion can be generated by friction between flow of this net work and the substrate.\n\nAuthors:\nElisabeth Ghabache\, Yuansheng Cao\, Yuchuan Miao*\, Alex Groisman\, Peter N. Devreotes*\, Wouter-Jan Rappel\n\ nDepartment of Physics\, University of California\, San Diego\, La Jolla\, California 92093\, USA\n*Department of Cell Biology\, Johns Hopkins Unive rsity\, Baltimore\, MD\, USA\n LOCATION:https://stable.researchseminars.org/talk/BIRS-21w5154/14/ END:VEVENT BEGIN:VEVENT SUMMARY:Ruth Baker (University of Oxford) DTSTART:20211019T205000Z DTEND:20211019T213000Z DTSTAMP:20260404T041840Z UID:BIRS-21w5154/15 DESCRIPTION:Title: Quantifying the impact of electric fields on single-cell moti lity\nby Ruth Baker (University of Oxford) as part of BIRS workshop Ma thematics of the Cell: Integrating Signaling\, Transport and Mechanics\n\n Abstract: TBA\n LOCATION:https://stable.researchseminars.org/talk/BIRS-21w5154/15/ END:VEVENT BEGIN:VEVENT SUMMARY:David Odde (University of Minnesot) DTSTART:20211019T220000Z DTEND:20211019T224000Z DTSTAMP:20260404T041840Z UID:BIRS-21w5154/16 DESCRIPTION:Title: Cellular sensing of material stiffness and negative durotaxis \nby David Odde (University of Minnesot) as part of BIRS workshop Math ematics of the Cell: Integrating Signaling\, Transport and Mechanics\n\n\n Abstract\nThe ability of cells to sense the mechanical stiffness of their environment is critical to their function\, and allows cells to migrate in a stiffness-dependent manner. In my talk I will describe how we have deve loped a computational motor-clutch model for the biophysics of cell migrat ion and applied it to glioma cell migration. Whereas an extensive literatu re across a wide range of cell types demonstrates the phenomenon of durota xis – the tendency of cells to migrate toward mechanically stiffer envir onments – we demonstrate that our motor-clutch cell migration model (Ban gasser et al.\, Nat Comm\, 2017) predicts “negative durotaxis” – bia sed migration toward softer environments – which we confirm experimental ly for the first time. Also\, we used the model to mechanically phenotype genetically induced glioma mouse models. The biophysical modeling and expe riments help point us toward potentially new therapeutic strategies.\n LOCATION:https://stable.researchseminars.org/talk/BIRS-21w5154/16/ END:VEVENT BEGIN:VEVENT SUMMARY:Daniel Coombs (University of British Columbia) DTSTART:20211019T224000Z DTEND:20211019T232000Z DTSTAMP:20260404T041840Z UID:BIRS-21w5154/17 DESCRIPTION:Title: A hierarchy of hidden Markov methods for single particle trac king\nby Daniel Coombs (University of British Columbia) as part of BIR S workshop Mathematics of the Cell: Integrating Signaling\, Transport and Mechanics\n\n\nAbstract\nHidden Markov models (HMM) provide a powerful too l for analysis of particle mobility. Briefly\, labelled objects are assume d to exist in discrete states\, where each state has a distinct mode of mo bility - commonly\, Brownian diffusion with a state-dependent diffusivity. In this talk\, I will describe a set of HMM\, beginning with simplest\, t wo-state model\, developing to many states\, and discussing how we can all ow for experimental positional uncertainties. I’ll show results using si mulated data\, as well as using experimental data for motion of membrane r eceptors on the surfaces of lymphocytes. The methods shown in this talk we re developed jointly with Raibatak Das\, Jennifer Morrison\, Suzanne ten H age and especially Rebeca Cardim Falcao.\n LOCATION:https://stable.researchseminars.org/talk/BIRS-21w5154/17/ END:VEVENT BEGIN:VEVENT SUMMARY:William Holmes (Vanderbilt) DTSTART:20211019T150000Z DTEND:20211019T154000Z DTSTAMP:20260404T041840Z UID:BIRS-21w5154/18 DESCRIPTION:Title: Modeling intra-cellular insulin transport dynamics in pancrea tic Beta cells ↓\nby William Holmes (Vanderbilt) as part of BIRS wor kshop Mathematics of the Cell: Integrating Signaling\, Transport and Mecha nics\n\n\nAbstract\nIn this talk\, I will discuss the role of cytoskeletal -mediated transport (by microtubules) in regulating insulin dynamics in pa ncreatic cells. Due to the increasing prevalence of diabetes and related d isorders\, understanding how individual cells regulate insulin availabilit y and secretion in response to glucose stimulation is of utmost importance . While it has been known for decades that dysregulated microtubule dynami cs alter insulin secretion\, their role in insulin regulation has been mur ky. Here I use computational modeling to demonstrate a new mechanism by wh ich apparently random trafficking of insulin on a random network of microt ubules regulates the intra-cellular localization and availability of insul in. These results demonstrate that microtubule mediated trafficking negati vely regulates insulin secretion. Accompanying experiments confirm this hy pothesis and demonstrate the potential for targeting of microtubule dynami cs to provide a new avenue to manipulate insulin secretion.\n LOCATION:https://stable.researchseminars.org/talk/BIRS-21w5154/18/ END:VEVENT BEGIN:VEVENT SUMMARY:Melissa Rolls (Penn State University) DTSTART:20211020T150000Z DTEND:20211020T154000Z DTSTAMP:20260404T041840Z UID:BIRS-21w5154/19 DESCRIPTION:Title: Mechanisms and modeling of neuronal microtubule dynamics and polarity\nby Melissa Rolls (Penn State University) as part of BIRS wor kshop Mathematics of the Cell: Integrating Signaling\, Transport and Mecha nics\n\n\nAbstract\nThe polarity and stability of the microtubule cytoskel eton are critical in supporting long-range directed transport of cellular cargo and long-term survival of neurons. However\, microtubules also need to be dynamic and reorganize in response to injury events. Using live imag ing and genetics\, multiple mechanisms that contribute to the primarily mi nus-end-out filament organization in Drosophila dendrites have been identi fied. These include local microtubule nucleation\, quality control of new microtubules and microtubule steering. Our objective is to understand how these complex mechanisms ensure both healthy function over long time perio ds and dramatic rearrangement in response to injury. To this end\, we prop ose a spatially-explicit mathematical model of the dendritic microtubule s ystem in Drosophila neurons. The stochastic modeling framework includes mi crotubule turnover dynamics and a spatial multiscale model that captures m icrotubule organization in branched dendrites. The model predicts the main tenance of polarity in simulated microtubule populations. Paired with biol ogical experiments\, this modeling framework has the potential to provide insight into the impact of turnover parameters as well as of individual po larity control mechanisms\, such as steering and nucleation\, on polarity and dynamics in Drosophila dendrites. Joint talk with Veronica Ciocanel.\n LOCATION:https://stable.researchseminars.org/talk/BIRS-21w5154/19/ END:VEVENT BEGIN:VEVENT SUMMARY:Peter Kramer (Rensselaer Polytechnic Institute) DTSTART:20211020T154000Z DTEND:20211020T162000Z DTSTAMP:20260404T041840Z UID:BIRS-21w5154/20 DESCRIPTION:Title: Spatial Parameterization of Attachment Processes in Molecular Motor-Cargo Systems\nby Peter Kramer (Rensselaer Polytechnic Institut e) as part of BIRS workshop Mathematics of the Cell: Integrating Signaling \, Transport and Mechanics\n\n\nAbstract\nIntracellular transport is condu cted largely by molecular motor proteins which process along cytoskeletal filaments\, from which they can attach or detach. We describe an analytica l framework to characterize motor attachment or reattachment rates to micr otubules as a function of the physical and geometric properties of the mot or\, the cargo to which it is attached\, and possibly a second motor attac hed to the same cargo and a microtubule. The biophysical model is coarse- grained at the level of the macromolecular motors and formulated in terms of stochastic differential equations\, allowing for rotation of the cargo and nonlinear force laws for the motor-cargo tether. Various asymptotic a pproximations based on ``small target'' first passage time calculations ar e possible depending on the relationship of the motor-cargo tether length\ , the distance between microtubules\, whether the cargo has a rigid or lip id membrane surface\, and the initial configuration of the motor and cargo relative to the microtubules. The same methodology also allows the compu tation of the probability distribution for which nearby microtubule a moto r will attach next. These results have potential application for modeling motor attachment in engineered systems where\, for example\, the cargo is introduced in a geometrically controlled way by optical trap or flow.\n LOCATION:https://stable.researchseminars.org/talk/BIRS-21w5154/20/ END:VEVENT BEGIN:VEVENT SUMMARY:Christine Payne (Duke) DTSTART:20211020T164000Z DTEND:20211020T172000Z DTSTAMP:20260404T041840Z UID:BIRS-21w5154/21 DESCRIPTION:Title: Intracellular transport of lysosomes decreases in the perinuc lear region: Insights from changepoint analysis\nby Christine Payne (D uke) as part of BIRS workshop Mathematics of the Cell: Integrating Signali ng\, Transport and Mechanics\n\n\nAbstract\nLysosomes are membrane-bound o rganelles responsible for processing endocytic molecules\, particles\, and viruses\, phagocytic destruction of pathogens\, and the cellular housekee ping of autophagy. These cellular functions require intracellular transpor t. A collaborative team led by Prof. Christine Payne in the Department of Mechanical Engineering and Materials Science at Duke University and Prof. Scott McKinley in the Department of Mathematics at Tulane University\, ena bled by the NSF-Simons Foundation Southeast Center for Mathematics and Bio logy (SCMB)\, has investigated the intracellular transport of these organe lles. We use fluorescence microscopy to characterize the motion of lysosom es as a function of intracellular region\, perinuclear or periphery\, and lysosome diameter. Single particle tracking data is complemented by change point identification and analysis of a mathematical model for state-switch ing. We classify motion as motile or stationary and then study how lysosom e location and diameter affects the proportion of time spent in each state and the speed during motile periods. We find that the proportion of time spent stationary is strongly region-dependent with significantly decreased motility in the perinuclear region. Increased diameter only slightly decr eases speed. These results show that intracellular region\, rather than ly sosome diameter\, is a major factor in the motion of lysosomes. Overall\, these results demonstrate the importance of decomposing particle trajector ies into qualitatively different behaviors before conducting population-wi de statistical analysis. This approach shows that intracellular region\, w hich is not regularly included as a factor in studies of intracellular tra nsport\, is a major factor.\n LOCATION:https://stable.researchseminars.org/talk/BIRS-21w5154/21/ END:VEVENT BEGIN:VEVENT SUMMARY:Scott McKinley (Tulane University) DTSTART:20211020T172000Z DTEND:20211020T180000Z DTSTAMP:20260404T041840Z UID:BIRS-21w5154/22 DESCRIPTION:Title: On the use and misuse of Bayesian methods for uncertainty qua ntification\nby Scott McKinley (Tulane University) as part of BIRS wor kshop Mathematics of the Cell: Integrating Signaling\, Transport and Mecha nics\n\n\nAbstract\nAn intrinsic challenge in studying intracellular trans port is that the time scale of experimental observation is far shorter tha n the time scales associated with many biological events of interest. This is why mathematical modeling is so important -- making good predictions i s impossible without good models -- but it can be difficult to associate p redictions with credible quantifications of uncertainty. In this talk\, i n which I will review a Bayesian approach to communicating predictions wit h uncertainty\, visiting some successes and failures I’ve experienced al ong the way. One issue that arises is that a “fully principled” UQ app roach can be computationally prohibitive\, and can even introduce biophysi cally unrealistic results. Some compromises must be made\, but where and h ow are open for debate. My hope is to open a conversation within the works hop about how others view the communication of uncertainty\, and whether a nd how we should teach these methods in our graduate programs.\n LOCATION:https://stable.researchseminars.org/talk/BIRS-21w5154/22/ END:VEVENT BEGIN:VEVENT SUMMARY:Alex Mogilner (New York University) DTSTART:20211021T150000Z DTEND:20211021T154000Z DTSTAMP:20260404T041840Z UID:BIRS-21w5154/23 DESCRIPTION:Title: Rapid and accurate assembly of mitotic spindle\nby Alex M ogilner (New York University) as part of BIRS workshop Mathematics of the Cell: Integrating Signaling\, Transport and Mechanics\n\n\nAbstract\nMitot ic spindle is a remarkable molecular machine segregating chromosomes and p ositioning\ncytokinetic ring prior to cell division. The spindle self-asse mbles from centrosomes\,\nmicrotubules and chromosomes very rapidly and ac curately. For decades\, the so-called\nsearch-and-capture model of this se lf-assembly was dominant. This model posited that\nthe microtubules random ly probe the cell space until\, by chance\, all chromosomes are\nconnected to the spindle. Recent data puts this model in doubt. I will show that bo th\ncurrent data and stochastic computational model argue that a much more deterministic \nprocess of polarity sorting in a complex microtubule-moto r system accounts for the rapid \nand accurate assembly of the spindle. No tably\, both centripetal chromosome transport\, and\nchromosome connection mechanics are the key to speed and accuracy.\n LOCATION:https://stable.researchseminars.org/talk/BIRS-21w5154/23/ END:VEVENT BEGIN:VEVENT SUMMARY:Samuel Isaacson (Boston University) DTSTART:20211021T154000Z DTEND:20211021T162000Z DTSTAMP:20260404T041840Z UID:BIRS-21w5154/24 DESCRIPTION:Title: Stochastic Reaction-Drift-Diffusion Methods for Studying Cell Signaling\nby Samuel Isaacson (Boston University) as part of BIRS wor kshop Mathematics of the Cell: Integrating Signaling\, Transport and Mecha nics\n\n\nAbstract\nParticle-based stochastic reaction-diffusion (PBSRD) m odels are one approach to study biological systems in which both the noisy diffusion of individual molecules\, and stochastic reactions between pair s of molecules\, may influence system behavior. They provide a more micros copic model than deterministic reaction-diffusion PDEs or stochastic react ion-diffusion SPDEs\, which treat molecular populations as continuous fiel ds. The reaction-diffusion master equation (RDME) and convergent RDME (CRD ME) are lattice PBSRD models\, with the latter providing a convergent appr oximation to the spatially-continuous volume-reactivity PBSRD model as the lattice spacing is taken to zero. In this talk I will present several gen eralizations of the RDME and CRDME to support spatial transport mechanisms needed for resolving spatially-distributed cellular signaling processes i n general geometries\, including drift due to background potentials\, inte raction potentials between molecules\, and continuous-time random walks to approximate molecular transport on surfaces.\n LOCATION:https://stable.researchseminars.org/talk/BIRS-21w5154/24/ END:VEVENT BEGIN:VEVENT SUMMARY:Fred Chang (UCSF) DTSTART:20211021T164000Z DTEND:20211021T172000Z DTSTAMP:20260404T041840Z UID:BIRS-21w5154/25 DESCRIPTION:Title: Role of osmotic forces in determining the size of the nucleus \nby Fred Chang (UCSF) as part of BIRS workshop Mathematics of the Cel l: Integrating Signaling\, Transport and Mechanics\n\n\nAbstract\nThe size of the nucleus scales with cell size so that the nuclear-to-cell volume r atio (NC Ratio) is maintained during cell growth. The mechanism responsibl e for this scaling is still mysterious. Nuclear volume is not determined m erely by DNA amount\, but is influenced by factors such and nuclear transp ort and nuclear envelope mechanics. Here\, we develop a quantitative model for nuclear size control and scaling based upon colloid osmotic pressure that is determined by numbers of macromolecules in the nucleoplasm and cyt oplasm. Osmotic shift experiments show that in the fission yeast\, the nu cleus behaves as an ideal osmometer. Perturbations that disrupt the relat ive numbers of macromolecules in each compartment lead to predictable chan ges in the NC ratio. Further this model provides an explanation for NC rat io homeostasis behavior. These studies highlight the primary role of osmot ic forces that determine the size of the nucleus and possibly other organe lles.\n LOCATION:https://stable.researchseminars.org/talk/BIRS-21w5154/25/ END:VEVENT BEGIN:VEVENT SUMMARY:Maitreyi Das (University of Tennessee Knoxville) DTSTART:20211021T172000Z DTEND:20211021T180000Z DTSTAMP:20260404T041840Z UID:BIRS-21w5154/26 DESCRIPTION:Title: Spatiotemporal regulation of Cdc42 activity organizes cytokin etic events\nby Maitreyi Das (University of Tennessee Knoxville) as pa rt of BIRS workshop Mathematics of the Cell: Integrating Signaling\, Trans port and Mechanics\n\n\nAbstract\nCell polarization is a fundamental proce ss by which proteins asymmetrically localize to their functional site in r esponse to a signal thus determining cell shape. One of the major regulato rs of polarization is the highly conserved small GTPase Cdc42. Cdc42 is ac tivated at the sites of cell growth in a dynamic manner. In fission yeast\ , active Cdc42 displays an anti-correlated oscillatory pattern that determ ines cell polarity and dimension. This oscillatory behavior of Cdc42 activ ation is an outcome of self-organizing positive and time-delayed negative feedback loops. Cdc42 is also activated at the division site during cytoki nesis\, but here it does not display a similar oscillatory pattern. Using the fission yeast model system\, we have shown that Cdc42 at the division site promotes polarization during cytokinesis. We find that once the actom yosin ring is assembled\, membrane trafficking at specific sites and times enables different steps in cytokinesis. Membrane trafficking events allow delivery of membrane and enzymes necessary for furrow formation and septu m/cell wall synthesis\, respectively. Later\, trafficking is also required for the delivery of glucanases that promote cell separation. It is not cl ear how the cell spatiotemporally organizes these precise membrane traffic king events during cytokinesis. We find that the Cdc42 activation pattern at the division site matches that of these trafficking events. This Cdc42 activity pattern spatiotemporally regulates membrane trafficking during c ytokinesis. Our data indicate that this pattern arises as a result of the interplay between the positive and negative regulators of Cdc42 which in t urn enables spatiotemporal organization of cytokinetic events. Understandi ng how the same regulators give rise to distinct activation patterns at th e cell ends compared to the division site will help to understand how cell s spatiotemporally organize complex multi-step events such as cytokinesis and polarized growth.\n LOCATION:https://stable.researchseminars.org/talk/BIRS-21w5154/26/ END:VEVENT BEGIN:VEVENT SUMMARY:Timothy Elston (University of North Carolina\, Chapel Hill) DTSTART:20211021T193000Z DTEND:20211021T201000Z DTSTAMP:20260404T041840Z UID:BIRS-21w5154/27 DESCRIPTION:Title: Modeling polarity establishment\nby Timothy Elston (Unive rsity of North Carolina\, Chapel Hill) as part of BIRS workshop Mathematic s of the Cell: Integrating Signaling\, Transport and Mechanics\n\nAbstract : TBA\n LOCATION:https://stable.researchseminars.org/talk/BIRS-21w5154/27/ END:VEVENT BEGIN:VEVENT SUMMARY:Dimitrios Vavylonis (Lehigh University) DTSTART:20211021T201000Z DTEND:20211021T205000Z DTSTAMP:20260404T041840Z UID:BIRS-21w5154/28 DESCRIPTION:Title: Cytoskeletal and membrane flows for cell polarization and mot ility\nby Dimitrios Vavylonis (Lehigh University) as part of BIRS work shop Mathematics of the Cell: Integrating Signaling\, Transport and Mechan ics\n\n\nAbstract\nThe ability of cells to polarize\, move by crawling\, o r divide\, requires coordinated interactions of the cytoskeleton with memb ranes as well as with signaling systems organizing on membranes. Predictiv e models of these mechanisms of subcellular organization requires accounti ng of how interactions at the molecular level lead to collective behavior involving patterns\, flows and forces over cellular scales. I will descri be two recent examples of how mathematical and computational modeling by o ur group was combined with experiments by collaborators to make progress o n understanding membrane and cytoskeletal flow and turnover at regions of cell extension. In the first example\, we showed that polarized exocytosis causes lateral membrane flows away from regions of membrane insertion. In rod-shaped fission yeast cells\, this causes membrane-bound inhibitors of Cdc42 with sufficiently low diffusion and/or detachment rates to deplete\ , thus patterning the growing cell tip in way that establishes its rod sha pe. In the second example\, we looked at actin cytoskeleton retrograde flo ws in regions of cell protrusion. Using filament-level kinetic and mechani cal models we provided an explanation of how distributed turnover through severing and annealing generates structural changes of Arp2/3-complex dend ritic networks. We also provide a filament-level implementation of the clu tch mechanism and force transmission through the whole lamellipodial actin network flowing over focal adhesions.\n LOCATION:https://stable.researchseminars.org/talk/BIRS-21w5154/28/ END:VEVENT BEGIN:VEVENT SUMMARY:Grace McLaughlin (University of North Carolina Chapel Hill) DTSTART:20211021T205000Z DTEND:20211021T213000Z DTSTAMP:20260404T041840Z UID:BIRS-21w5154/29 DESCRIPTION:Title: Modeling Asynchronous Nuclear Division\nby Grace McLaughl in (University of North Carolina Chapel Hill) as part of BIRS workshop Mat hematics of the Cell: Integrating Signaling\, Transport and Mechanics\n\n\ nAbstract\nMultinucleate cells are common in biology\, with examples inclu ding muscle cells\, placenta\, and fungi. Despite this\, many aspects of t heir cell biology are not well understood. Dividing nuclei residing in a c ommon cytosol would be expected to synchronize\, as the oscillating levels of cell cycle regulators from each nucleus should in theory entrain neigh bors. However\, in the multinucleate fungus Ashbya Gossypii\, spatially ne ighboring nuclei have been observed to divide out of sync. Here we mathema tically model Ashbya nuclei as a dynamically growing system of coupled pha se oscillators to determine possible mechanisms that could lead to asynchr onous division. Nuclear movement in space is modeled to capture core featu res of Ashbya nuclear dynamics\, including both repulsion of and rearrange ment with neighbors. We study the effects of mobility\, cytosolic compartm entalization\, inhibitory signals\, and noise on transient phase dynamics. To compare the model with experimental results\, we develop a nuclear tr acking pipeline with the aim of tracking nuclei during bypassing events\, identifying nuclear division\, and linking nuclei into hyphae. Initial res ults suggest a combination of locally and globally acting mechanisms might be at play leading to the observed dynamics in Ashbya.\n LOCATION:https://stable.researchseminars.org/talk/BIRS-21w5154/29/ END:VEVENT BEGIN:VEVENT SUMMARY:Jian Liu (Johns Hopkins University) DTSTART:20211021T220000Z DTEND:20211021T224000Z DTSTAMP:20260404T041840Z UID:BIRS-21w5154/30 DESCRIPTION:Title: Spatial control over near-critical-point operation ensures fi delity of ParABS-mediated DNA partition\nby Jian Liu (Johns Hopkins Un iversity) as part of BIRS workshop Mathematics of the Cell: Integrating Si gnaling\, Transport and Mechanics\n\n\nAbstract\nIn bacteria\, most low-co py-number plasmid and chromosomally encoded partition systems belong to th e tripartite ParABS partition machinery. Despite the importance in genetic inheritance\, the mechanisms of ParABS-mediated genome partition are not well understood. Combining theory and experiment\, we provided evidence th at the ParABS system – DNA partitioning in vivo via the ParA gradient-ba sed Brownian ratcheting – operates near a transition point in parameter space (i.e.\, a critical point)\, across which the system displays qualita tively different motile behaviors. This near-critical-point operation adap ts the segregation distance of replicated plasmids to the half-length of t he elongating nucleoid\, ensuring both cell halves to inherit one copy of the plasmids. Further\, we demonstrated that the plasmid localizes the cyt oplasmic ParA to buffer the partition fidelity against the large cell-to-c ell fluctuations in ParA level. The spatial control over the near-critical -point operation not only ensures both sensitive adaption and robust execu tion of partitioning\, but also sheds light on the fundamental question in cell biology: How do cells faithfully measure cellular-scale distance by only using molecular-scale interactions?\n LOCATION:https://stable.researchseminars.org/talk/BIRS-21w5154/30/ END:VEVENT BEGIN:VEVENT SUMMARY:Will Hancock (Penn State University) DTSTART:20211021T224000Z DTEND:20211021T232000Z DTSTAMP:20260404T041840Z UID:BIRS-21w5154/31 DESCRIPTION:Title: The role of the fluid lipid bilayer in kinesin-driven vesicle transport\nby Will Hancock (Penn State University) as part of BIRS wo rkshop Mathematics of the Cell: Integrating Signaling\, Transport and Mech anics\n\n\nAbstract\nMost cargo carried by kinesin motors are membrane bou nd\, which has implications for motor-based transport. We are investigati ng the role of membrane fluidity in kinesin-based transport using two geom etries – a supported lipid bilayer and free vesicles. From attaching mo tors to a supported lipid bilayer\, we can estimate the effect of the memb rane on motor on- and off-rates. By taking these values\, we can interpre t our vesicle experiments where we find that run length increases with inc reasing motor numbers. Notably\, clustering motors enhances the motor run length\, showing that the geometry of motor attachment to lipid bilayers may be a regulator of bidirectional transport.\n LOCATION:https://stable.researchseminars.org/talk/BIRS-21w5154/31/ END:VEVENT BEGIN:VEVENT SUMMARY:Khanh Dao Duc (University of British Columbia) DTSTART:20211022T150000Z DTEND:20211022T154000Z DTSTAMP:20260404T041840Z UID:BIRS-21w5154/32 DESCRIPTION:Title: Impact of ribosomes on translation across scales and new metr ics for biological shape analysis\nby Khanh Dao Duc (University of Bri tish Columbia) as part of BIRS workshop Mathematics of the Cell: Integrati ng Signaling\, Transport and Mechanics\n\nAbstract: TBA\n LOCATION:https://stable.researchseminars.org/talk/BIRS-21w5154/32/ END:VEVENT BEGIN:VEVENT SUMMARY:Jay Newby (University of Alberta) DTSTART:20211022T154000Z DTEND:20211022T162000Z DTSTAMP:20260404T041840Z UID:BIRS-21w5154/33 DESCRIPTION:Title: Dynamic self organization and microscale fluid properties of nucleoplasm\nby Jay Newby (University of Alberta) as part of BIRS work shop Mathematics of the Cell: Integrating Signaling\, Transport and Mechan ics\n\n\nAbstract\nThe principal function of the nucleus is to facilitate storage\, retrieval\, and maintenance of the genetic information. A unique feature of nucleoplasm—the fluid of the nucleus—is that it contains c hromatin (DNA) and RNA. In contrast to other important biological polymer hydrogels\, such as mucus and extracellular matrix\, the nucleic acid poly mers have a sequence that encodes both genetic information and strongly in fluences spatial organization. How does crowding in a sequence specific hy drogel influence spatial organization of the dynamic molecular components responsible for nuclear function? We are becoming increasingly aware of th e role of liquid-liquid phase separation (LLPS) in cellular processes in t he nucleus and the cytoplasm. Complex molecular interactions over a wide r ange of timescales can cause large biopolymers (RNA\, protein\, etc) to ph ase separate from the surrounding nucleoplasm or cytoplasm into distinct b iocondensates (spherical droplets in the simplest cases). I will discuss r ecent work modelling the role of nuclear biocondensates in neurodegenerati ve disease and several ongoing projects related to modelling and microscop y image analysis.\n LOCATION:https://stable.researchseminars.org/talk/BIRS-21w5154/33/ END:VEVENT BEGIN:VEVENT SUMMARY:Tom Chou (UCLA) DTSTART:20211022T164000Z DTEND:20211022T172000Z DTSTAMP:20260404T041840Z UID:BIRS-21w5154/34 DESCRIPTION:Title: Biophysics of X-inactivation and integration site T cell popu lations in HIV-infected individuals\nby Tom Chou (UCLA) as part of BIR S workshop Mathematics of the Cell: Integrating Signaling\, Transport and Mechanics\n\nAbstract: TBA\n LOCATION:https://stable.researchseminars.org/talk/BIRS-21w5154/34/ END:VEVENT END:VCALENDAR