Mathematical modeling of biological dynamics

Li, Xiaochu

Mathematical modeling of biological dynamics

dc.contributor.author	Li, Xiaochu	en
dc.contributor.committeechair	Chen, Jing	en
dc.contributor.committeemember	Tauber, Uwe C.	en
dc.contributor.committeemember	Cimini, Daniela	en
dc.contributor.committeemember	Scharf, Birgit	en
dc.contributor.committeemember	Childs, Lauren Maressa	en
dc.contributor.department	Biological Sciences	en
dc.date.accessioned	2023-12-12T04:00:12Z	en
dc.date.available	2023-12-12T04:00:12Z	en
dc.date.issued	2023-12-11	en
dc.description.abstract	This dissertation unravels intricate biological dynamics in three distinct biological systems as the following. These studies combine mathematical models with experimental data to enhance our understanding of these complex processes. 1. Bipolar Spindle Assembly: Mitosis relies on the formation of a bipolar mitotic spindle, which ensures an even distribution of duplicated chromosomes to daughter cells. We address the issue of how the spindle can robustly recover bipolarity from the irregular forms caused by centrosome defects/perturbations. By developing a biophysical model based on experimental data, we uncover the mechanisms that guide the separation and/or clustering of centrosomes. Our model identifies key biophysical factors that play a critical role in achieving robust spindle bipolarization, when centrosomes initially organize a monopolar or multipolar spindle. These factors encompass force fluctuations between centrosomes, balance between repulsive and attractive inter-centrosomal forces, centrosome exclusion from the cell center, proper cell size and geometry, and limitation of the centrosome number. 2. Chromosome Oscillation: During mitotic metaphase, chromosomes align at the spindle equator in preparation for segregation, and form the metaphase plate. However, these chromosomes are not static; they exhibit continuous oscillations around the spindle equator. Notably, either increasing or decreasing centromeric stiffness in PtK1 cells can lead to prolonged metaphase chromosome oscillations. To understand this biphasic relationship, we employ a force-balance model to reveal how oscillation arises in the spindle, and how the amplitude and period of chromosome oscillations depend on the biological properties of spindle components, including centromeric stiffness. 3. Pattern Formation in Bacterial-Phage Systems: The coexistence of bacteriophages (phages) and their host bacteria is essential for maintaining microbial communities. In resource-limited environments, mobile bacteria actively move toward nutrient-rich areas, while phages, lacking mobility, infect these motile bacterial hosts and disperse spatially through them. We utilize a combination of experimental methods and mathematical modeling to explore the coexistence and co-propagation of lytic phages and their mobile host bacteria. Our mathematical model highlights the role of local nutrient depletion in shaping a sector-shaped lysis pattern in the 2D phage-bacteria system. Our model further shows that this pattern, characterized by straight radial boundaries, is a distinctive indicator of extended coexistence and co-propagation of bacteria and phages. Such patterns rely on a delicate balance among the intrinsic biological characteristics of phages and bacteria, which have likely arisen from the coevolution of cognate pairs of phages and bacteria.	en
dc.description.abstractgeneral	Mathematical modeling is a powerful tool for studying intricate biological dynamics, as modeling can provide a comprehensive and coherent picture about the system of interest that facilitates our understanding, and can provide ways to probe the system that are otherwise impossible through experiments. This dissertation includes three studies of biological dynamics using mathematical modeling: 1. Bipolar Spindle Assembly: Mitotic spindle is a bipolar subcellular structure that self-assembles during cell division. The spindle ensures an even distribution of duplicated chromosomes into two daughter cells. Certain perturbations can cause the spindle to assemble abnormally with one pole or more than two poles, which would cause the daughter cells to inherit incorrect number of chromosomes and die from the error. However, the cell is surprisingly good at correcting these spindle abnormalities and recovering the bipolar spindle. Here we build a model to explore how the cell achieves such recoveries and preferentially form a bipolar spindle to rescue itself. 2. Chromosome Oscillation: In mitotic metaphase, chromosomes are aligned at the spindle equator before they segregate. Interestingly, unlike the cartoon images in textbooks, the aligned chromosomes often move rhythmically around the spindle equator. We used a mathematical model to unravel how the chromosome oscillation arises and how it depends on the biological properties of the spindle components, such as stiffness of the centromere, the structure that connects the two halves of duplicated chromosomes. 3. Pattern Formation in Bacterial-Phage System: Phages are viruses that hijack their host bacteria for proliferation and spreading. In this study we developed a mathematical model to elucidate a common lysis pattern that forms when expanding host bacterial colony encounters phages. Interestingly, our model revealed that such a lysis pattern is a telltale sign that the bacterium-phage pair have achieved a delicate balance between each other and are capable of spreading together over a long period of time.	en
dc.description.degree	Doctor of Philosophy	en
dc.format.medium	ETD	en
dc.identifier.other	vt_gsexam:39074	en
dc.identifier.uri	https://hdl.handle.net/10919/117179	en
dc.language.iso	en	en
dc.publisher	Virginia Tech	en
dc.rights	In Copyright	en
dc.rights.uri	http://rightsstatements.org/vocab/InC/1.0/	en
dc.subject	Mathematical modeling	en
dc.subject	centrosome clustering	en
dc.subject	chromosome oscillation	en
dc.subject	pattern formation	en
dc.title	Mathematical modeling of biological dynamics	en
dc.type	Dissertation	en
thesis.degree.discipline	Biological Sciences	en
thesis.degree.grantor	Virginia Polytechnic Institute and State University	en
thesis.degree.level	doctoral	en
thesis.degree.name	Doctor of Philosophy	en