Biology subjects

Chu, W.-T.

Publications and source records attributed to Chu, W.-T..

3 recordsLinked to original sources

bioRxiv2023

Uncovering the lung cancer mechanisms through the chromosome structural ensemble characteristics

Lung cancer is one of the most common cancers in human. However, it is still lack of understanding the mechanisms of a normal cell developing to the cancer cell. Here we develop the chromosome dynamic structural model and quantify the important characteristics of the chromosome structural ensemble of the normal lung cell and the lung cancer A549 cell. Our results demonstrate the essential relationship among the chromosome ensemble, the epigenetic marks, and the gene expressions, which suggests the linkage between chromosome structure and function. The analysis reveals that the lung cancer cell may have higher level of relative ensemble fluctuation as well as higher degree of the phase separation between the two compartments than the normal lung cells. In addition, the significant conformational "switching off" events (from compartment A to B) are more than the significant conformational "switching on" events during the lung cancerization. The kinetic lung cancerization pathway is not the same as the reversion pathway by characterizing the hot spots and interaction networks of the lung cancer transitions. These investigations have revealed the cell fate determination mechanism of the lung cancer process, which will be helpful for the further prevention and control of cancers.

biophysics↗

bioRxiv2020

Efficient cooperation of chloroplasts and mitochondria enhances ATP and sucrose production

Efficient photosynthesis requires a balance of ATP and NADPH production/consumption in chloroplasts and the exportation of reducing equivalents from chloroplasts is important for balancing stromal ATP/NADPH ratio. Here we showed that the overexpression of purple acid phosphatase 2 on the outer membranes of chloroplasts and mitochondria can streamline the production and consumption of reducing equivalents in these two organelles, respectively. A higher capacity of consumption of reducing equivalents in mitochondria can indirectly help chloroplasts to balance the ATP/NADPH ratio in stroma and recycle NADP+, the electron acceptors of the linear electron flow. A higher rate of ATP and NADPH production from the linear electron flow, a higher capacity of carbon fixation by the Calvin-Benson-Bassham cycle and a greater consumption of NADH in mitochondria, enhance photosynthesis in the chloroplasts, ATP production in the mitochondria, sucrose synthesis in the cytosol, and eventually boosting plant growth and seed yields in the overexpression lines.

plant biology↗

bioRxiv2019

Investigations of the Underlying Mechanisms of HIF-1α and CITED2 Binding to TAZ1

The TAZ1 domain of CREB binding protein is crucial for transcriptional regulation and recognizes multiple targets. The interactions between TAZ1 and its specific targets are related to the cellular hypoxic negative feedback regulation. Previous experiments reported that one of the TAZ1 targets CITED2 is an efficient competitor of another target HIF-1. Here by developing the structure-based models of TAZ1 complexes we have uncovered the underlying mechanisms of the competitions between HIF-1 and CITED2 binding to TAZ1. Our results are consistent with the experimental hypothesis on the competition mechanisms and the apparent affinity. In addition, the simulations prove the dominant position of forming TAZ1-CITED2 complex in both thermodynamics and kinetics. For thermodynamics, TAZ1-CITED2 is the lowest basin located on the free energy surface of binding in the ternary system. For kinetics, the results suggest that CITED2 binds to TAZ1 faster than HIF-1. Besides, the analysis of contact map and{phi} values in this study will be helpful for further experiments on TAZ1 systems.

biophysics↗