Biology subjects

Seirin-Lee, S.

Publications and source records attributed to Seirin-Lee, S..

5 recordsLinked to original sources

bioRxiv2025

Imaging Data-based Model Description Combining OptimalTransport and Phase-field Model

The geometrical properties of a cell are not merely passive consequences of cellular function but actively regulate key biological processes during development, morphogenesis, and disease. Although modern live-imaging techniques now allow detailed monitoring of cell morphology, incorporating such complex geometrical information into mathematical models has remained a major challenge. Conventional modeling approaches often rely on artificial cell shape assumptions or purely in silico constructions, and discrete imaging data remain fundamentally mismatched with continuous biochemical models based on differential equations. As a result, current models struggle to accurately reproduce biochemical dynamics within realistic, dynamically changing cell geometries. To overcome these limitations, we establish a novel mathematical framework, Imaging Data-based Model Description (IDMD), which integrates Optimal Transport (OT) theory with phase-field (PF) modeling to bridge imaging data and mathematical models. Using live-imaging data from in vitro cultured cells and the one-cell C. elegans embryo, we demonstrate the versatility of our framework. By directly incorporating real cell geometry into mathematical modeling, our framework provides a powerful new avenue for investigating how geometrical constraints regulate biochemical pattern formation and cell-fate decisions. More broadly, this study highlights a promising direction for integrating modern data science techniques with mathematical modeling, opening new conceptual and methodological possibilities for understanding geometry-driven biological processes in development and disease.

biophysics↗

bioRxiv2024

Optimal targeted therapy for multiple cancers based on contrastive Notch signaling networks

Over decades, cancer understanding has advanced significantly at molecular and cellular levels, leading to various therapies based on intra-/inter-cellular networks. Despite this, cancer still remains a leading cause of death globally. The primary driver of cancer mortality is metastasis, responsible for about 90% of cancer deaths, due to unclear pathophysiological mechanisms that complicate treatment development. The Notch signaling pathway, a crucial intercellular network in many cancers, has been extensively studied and therapies targeting the Notch pathway also have been well-studied based on inhibiting various stages of Notch activation. On the other hand, Notch signalings role varies between cancers; for instance, in non-small cell lung cancer, Notch1 and Notch2 have opposing effects compared to their roles in embryonal brain tumors. In this study, we assumed a scenario of multiple cancers with contrasting Notch signaling pathways and explored optimal targeted therapies for reducing cancer cells by developing two mathematical models with contrasting Notch signaling pathways. The proposed therapies were compared with existing ones, and strategies were investigated to reduce cancer cell numbers for different stage of cancer. We found that that multiple cancers with contrasting Notch networks can be controlled by a common targeted signal network. Combination therapy enhancing Notch production may be most effective in early-stage cancer, while cleavage therapies may be more effective in late-stage cancer. Our study also suggests that optimal treatment should consider the cancer stage, with careful selection and ordering of medication therapies.

cancer biology↗

bioRxiv2023

Turing pattern formation in reaction-cross-diffusion systems with a bilayer geometry

Conditions for self-organisation via Turings mechanism in biological systems represented by reaction-diffusion or reaction-cross-diffusion models have been extensively studied. Nonetheless, the impact of tissue stratification in such systems is under-explored, despite its ubiquity in the context of a thin epithelium overlying connective tissue, for instance the epidermis and underlying dermal mesenchyme of embryonic skin. In particular, each layer can be subject to extensively different biochemical reactions and transport processes, with chemotaxis - a special case of cross- diffusion - often present in the mesenchyme, contrasting the solely molecular transport typically found in the epidermal layer. We study Turing patterning conditions for a class of reaction-cross- diffusion systems in bilayered regions, with a thin upper layer and coupled by a linear transport law. In particular, the role of differential transport through the interface is explored together with the presence of asymmetry between the homogeneous equilibria of the two layers. A linear stability analysis is carried out around a spatially homogeneous equilibrium state in the asymptotic limit of weak and strong coupling strengths, where quantitative approximations of the bifurcation curve can be computed. Our theoretical findings, for an arbitrary number of reacting species, reveal quantitative Turing conditions, highlighting when the coupling mechanism between the layered regions can either trigger patterning or stabilize a homogeneous equilibrium regardless of the inde- pendent patterning state of each layer. We support our theoretical results through direct numerical simulations, and provide an open source code to explore such systems further.

developmental biology↗

bioRxiv2022

The optimal strategy of incompatible insect technique (IIT) using Wolbachia to control Malaria

For decades, techniques to control vector population with low environmental impact have been widely explored in both field and theoretical studies. The incompatible insect method (IIT) using Wolbachia, based on cytoplasmic incompatibility, is a technique that Wolbachia-infected male mosquitoes are incapable of producing viable offspring after mating with wildtype female mosquitoes. While the IIT method experimentally ensured its effectiveness in several field works, the failure of female mosquito population control owing to the accidental contamination of Wolbachia-infected female mosquitoes has been a concern and an obstacle in implementing the IIT method in nature. In this study, we developed a population-based IIT mathematical model using cytoplasmic incompatibility and evaluated the effectiveness of the IIT method in scenarios where contamination was present or absent. In addition, by extending the model to assess the disease infection status of the human population with malaria, we evaluated the optimal release strategy and cost for successful disease control. Our study proves that IIT could be a promising method to control mosquito-borne diseases without perfect eradication of vector mosquito population regardless of contamination.

pathology↗

bioRxiv2021

The extra-embryonic space is a geometric constraint regulating cell arrangement in nematodes

In multicellular systems, cells communicate with adjacent cells to decide their positions and fates. Cellular arrangement in space is thus important for development. Orientation of cell division, cell-cell interaction (i.e., attraction and repulsion), and geometrical constraints are the three major factors that define cell arrangement. Here we found that the amount and location of extra-embryonic space (ES), the empty space within the eggshell not occupied by embryonic cells, are critical to define cell arrangement in the 4-cell stage embryo of nematodes. This discovery was motivated by observations of a T-reversed-type arrangement, which was not explained by a model assuming simplified shapes of the eggshell, in our previous experiments. In this study, we incorporated the precise shape of the C. elegans eggshell in our newly developed multicellular morphology model based on the phase-field method. The new model succeeded in reproducing the T-reverse arrangement, demonstrating the importance of the precise shape of the eggshell. Further analyses revealed that the amount and location of ES is critical to develop various cell arrangements. Overall, our analyses characterized the roles of new geometrical contributors to cell arrangements, which should be considered for any multicellular system.

biophysics↗