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Browsing by Author "Li, Xiaochu"

Now showing 1 - 4 of 4
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    A fine balance among key biophysical factors is required for recovery of bipolar mitotic spindle from monopolar and multipolar abnormalities
    Li, Xiaochu; Bloomfield, Mathew; Bridgeland, Alexandra; Cimini, Daniela; Chen, Jing (American Society for Cell Biology, 2023-06-21)
    During mitosis, equal partitioning of chromosomes into two daughter cells requires assembly of a bipolar mitotic spindle. Because the spindle poles are each organized by a centrosome in animal cells, centrosome defects can lead to monopolar or multipolar spindles. However, the cell can effectively recover the bipolar spindle by separating the centrosomes in monopolar spindles and clustering them in multipolar spindles. To interrogate how a cell can separate and cluster centrosomes as needed to form a bipolar spindle, we developed a biophysical model, based on experimental data, which uses effective potential energies to describe key mechanical forces driving centrosome movements during spindle assembly. Our model identified general biophysical factors crucial for robust bipolarization of spindles that start as monopolar or multipolar. These factors include appropriate force fluctuation between centrosomes, balance between repulsive and attractive forces between centrosomes, exclusion of the centrosomes from the cell center, proper cell size and geometry, and a limited centrosome number. Consistently, we found experimentally that bipolar centrosome clustering is promoted as mitotic cell aspect ratio and volume decrease in tetraploid cancer cells. Our model provides mechanistic explanations for many more experimental phenomena and a useful theoretical framework for future studies of spindle assembly.
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    Formation of phage lysis patterns and implications on co-propagation of phages and motile host bacteria
    Li, Xiaochu; Gonzalez, Floricel; Esteves, Nathaniel; Scharf, Birgit E.; Chen, Jing (2020-03)
    Coexistence of bacteriophages, or phages, and their host bacteria plays an important role in maintaining the microbial communities. In natural environments with limited nutrients, motile bacteria can actively migrate towards locations of richer resources. Although phages are not motile themselves, they can infect motile bacterial hosts and spread in space via the hosts. Therefore, in a migrating microbial community coexistence of bacteria and phages implies their co-propagation in space. Here, we combine an experimental approach and mathematical modeling to explore how phages and their motile host bacteria coexist and co-propagate. When lytic phages encountered motile host bacteria in our experimental set up, a sector-shaped lysis zone formed. Our mathematical model indicates that local nutrient depletion and the resulting inhibition of proliferation and motility of bacteria and phages are the key to formation of the observed lysis pattern. The model further reveals the straight radial boundaries in the lysis pattern as a telltale sign for coexistence and co-propagation of bacteria and phages. Emergence of such a pattern, albeit insensitive to extrinsic factors, requires a balance between intrinsic biological properties of phages and bacteria, which likely results from coevolution of phages and bacteria. Author summary Coexistence of phages and their bacterial hosts is important for maintaining the microbial communities. In a migrating microbial community, coexistence between phages and host bacteria implies that they co-propagate in space. Here we report a novel phage lysis pattern that is indicative of this co-propagation. The corresponding mathematical model we developed highlights a crucial dependence of the lysis pattern and implied phage-bacteria co-propagation on intrinsic properties allowing proliferation and spatial spreading of the microbes. In contrast, extrinsic factors, such as overall nutrient level, do not influence phage-bacteria coexistence and co-propagation. Findings from this work have strong implications for dispersal of phages mediated by motile bacterial communities, which will provide scientific basis for the fast-growing applications of phages.
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    Joint Biomedical Event Extraction and Entity Linking via Iterative Collaborative Training
    Li, Xiaochu (Virginia Tech, 2023-05)
    Biomedical entity linking and event extraction are two crucial tasks to support text understanding and retrieval in the biomedical domain. These two tasks intrinsically benefit each other: entity linking disambiguates the biomedical concepts by referring to external knowledge bases and the domain knowledge further provides additional clues to understand and extract the biological processes, while event extraction identifies a key trigger and entities involved to describe each biological process which also captures the structural context to better disambiguate the biomedical entities. However, previous research typically solves these two tasks separately or in a pipeline, leading to error propagation. What's more, it's even more challenging to solve these two tasks together as there is no existing dataset that contains annotations for both tasks. To solve these challenges, we propose joint biomedical entity linking and event extraction by regarding the event structures and entity references in knowledge bases as latent variables and updating the two task-specific models in an iterative training framework: (1) predicting the missing variables for each partially annotated dataset based on the current two task-specific models, and (2) updating the parameters of each model on the corresponding pseudo completed dataset. Experimental results on two benchmark datasets: Genia 2011 for event extraction and BC4GO for entity linking, show that our joint framework significantly improves the model for each individual task and outperforms the strong baselines for both tasks. We will make the code and model checkpoints publicly available once the paper is accepted.
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    Mathematical modeling of biological dynamics
    Li, Xiaochu (Virginia Tech, 2023-12-11)
    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.