MS04 - CDEV-1
Cartoon Room 2 (#3147) in The Ohio Union

Data-driven, modeling, and topological techniques in cell and developmental biology

Tuesday, July 18 at 04:00pm

SMB2023 SMB2023 Follow Tuesday during the "MS04" time block.
Room assignment: Cartoon Room 2 (#3147) in The Ohio Union.
Note: this minisymposia has multiple sessions. The other session is MS03-CDEV-1 (click here).

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Alexandria Volkening, Andreas Buttenschoen, Veronica Ciocanel


Cell and developmental biology spans many interconnected temporal and spatial scales, including carefully orchestrated genetic regulatory networks and other intracellular dynamics, interactions between pairs of cells, and the collective behavior of thousands of cells during tissue formation or disease-related tissue disruption. Whether focused on questions such as how cells make decisions about their fate, respond to external signals, regulate their shape, migrate, or communicate with one another, the mathematical methods that researchers develop to address these questions are similarly broad and interconnected. Motivated by these observations, our minisymposium brings together scientists addressing a wide range of biological questions using data-driven approaches, mathematical modeling, or topological techniques. Our goal is to showcase mathematically complementary approaches and highlight interconnected questions in cell and developmental biology.

Joel Dokmegang

Northwestern University (Molecular Biosciences)
"Spectral Decomposition of Morphogenesis"
Describing morphogenesis generally consists in aggregating the multiple high resolution spatiotemporal processes involved into repeatable low resolution morphological stories consistent across sample individuals of the same species or group. In order to achieve this goal, biologists have often had to submit movies issued from live imaging of developing embryos either to the eye test or to basic statistical analysis. Although successful, these methods however present noticeable drawbacks, as they can be time consuming, hence unfit for scale, and often lack standardisation. In this work, we leverage the power of continuum mechanics and spectral decomposition to propose a standardised framework for automatic detection and timing of morphological processes. First, we quantify shape changes in gastrulating ascidian embryos by evaluating strain-rate tensor fields at their surface. We then apply to this data a generalised Fourier transform, resulting in canonical spatio-temporal atlases that tell the story of morphogenesis in the studied embryos.

John Nardini

The College of New Jersey (Mathematics & Statistics)
"Statistical and Topological Summaries Aid Disease Detection for Segmented Retinal Vascular Images"
Microvascular disease complications can alter vascular network morphology and disrupt tissue functioning. Such diseases are typically assessed by visual inspection of retinal images, but this can be challenging when diseases exhibit silent symptoms or patients cannot attend in-person meetings. We propose that statistical and topological summaries of segmented retinal vascular images provide promising avenues to automate and aid microvascular disease status and examine the performance of machine learning algorithms in detecting microvascular disease from these summaries. We apply our methods to three datasets and find that, among the 13 descriptor vectors we consider, either a statistical Box-counting descriptor vector or a topological Flooding descriptor vector achieves the highest accuracy levels. When we apply our methods to a fourth dataset consisting of data from multiple data sources, the Box-counting vector maintains its strong performance while the topological Flooding vector which is sensitive to differences in the annotation styles between the different datasets. Our work represents a first step to establishing which computational methods are most suitable for identifying microvascular disease as well as some of their current limitations. In the longer term, these methods could be incorporated into automated disease assessment tools.
Additional authors: Charles Pugh, University of Oxford; Helen Byrne, University of Oxford.

Anna Nelson

Duke University (Department of Mathematics)
"Mathematical modeling of microtubule assembly and polarity in dendrites"
The microtubule cytoskeleton is responsible for sustained, long-range transport of cellular cargo inside neurons. However, microtubules must also be dynamic and rearrange their orientation, or polarity, in response to injuries. While mechanisms that control the minus-end out microtubule orientation in Drosophila dendrites have been identified experimentally, it is unknown how these mechanisms maintain both dynamic rearrangement and sustained, long-term function of the cell. To better understand these mechanisms, we introduce a spatially-explicit mathematical model of dendritic microtubule growth dynamics using parameters informed by experimental data. We explore several hypotheses of microtubule growth using both a stochastic model and a continuum model, and use fluorescence microscopy experiments to validate mechanisms such as limited tubulin availability and catastrophe events that depend on microtubule length. By incorporating biological experiments, our modeling framework can uncover the impact of various mechanisms on the collective dynamics and polarity of microtubules in Drosophila dendrites.
Additional authors: Veronica Ciocanel, Duke University; Scott McKinley, Tulane University; Melissa Rolls, Pennsylvania State University

Shayne M. Plourde

the Ohio State University (Molecular, Cellular, and Developmental Biology Program)
"Asymmetric Centrosome Maturation in the Early C. elegans Embryo: Insights from Multi-scale Microscopy and Modeling"
Centrosomes are nucleus-associated organelles made up of a pair of tubular centrioles surrounded by a cloud of pericentriolar material. Centrosomes serve as the nucleation site for microtubule arrays that interact with motor proteins at the periphery of the cell which act together to position the nucleus prior to division. Proper positioning is especially important in asymmetric cell division, where daughter cells inherit unequal amounts of specific factors. How the two centriole pairs, and their centrosomes, are positioned is critically important to stem cell development and perturbations in this process can be observed in cancer metastasis. In the C. elegans first cell cycle, proper positioning of the centrosomes is required for the asymmetric division used to determine the germline lineage of cells. Previous work has shown an asymmetry in the microtubule arrays nucleated by the two centrosomes that set up these divisions. However, the functional origin of this asymmetry is unknown. Using in vivo data of the recruitment and recovery of GFP tagged AIR-1, a protein that localizes to centrosomes in the early C. elegans embryo, we parameterized a mathematical model of centrosome maturation. Analysis of a large set of parameters that fit our model to the in vivo data reveal that there are potential differences in the dynamics between the two centrosomes. Further, we tracked the inheritance of the oldest centrioles into the 4 cell stage and observed a potential age related inheritance pattern. The multi-scale microscopy and mathematical modeling together support our hypothesis that there is a previously uncharacterized asymmetry inside of the C. elegans centrosome that could be connected to cell fate decisions.
Additional authors: Natalia Kravtsova, OSU Department of Mathematics; Adriana T. Dawes, OSU Department of Mathematics/Molecular Genetics

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