arXiv subjects

Dianjie Li

Publications and source records attributed to Dianjie Li.

3 recordsLinked to original sources

arXiv2024

Nonequilibrium and nonlinear kinetics as key determinants for bistability in fission yeast G2-M transition

A living cell is an open, nonequilibrium biochemical system where ATP hydrolysis serves as the energy source for a wide range of intracellular processes, possibly including the assurance for decision-making. In the fission yeast cell cycle, the transition from G2 to M phase is driven by the activation of Cdc13/Cdc2 and Cdc25 and the deactivation of Wee1 through phosphorylation-dephosphorylation cycles with feedback loops. Here, we present a kinetic description of the G2-M circuit which reveals that both cellular ATP level and ATP hydrolysis free energy critically control Cdc2 activation. Using fission yeast nucleoplasmic extract (YNPE), we experimentally verify that increased ATP level drives the activation of Cdc2 which exhibits bistability and hysteresis in response to changes in cellular ATP level and ATP hydrolysis energy. These findings suggest that cellular ATP level and ATP hydrolysis energy are determinants of the bistability and robustness of Cdc2 activation during G2-M transition.

q-bio.MN↗

arXiv2022

Modeling COVID-19 vaccine-induced immunological memory development and its links to antibody level and infectiousness

COVID-19 vaccines have proven to be effective against SARS-CoV-2 infection. However, the dynamics of vaccine-induced immunological memory development and neutralizing antibodies generation are not fully understood, limiting vaccine development and vaccination regimen determination. Herein, we constructed a mathematical model to characterize the vaccine-induced immune response based on fitting the viral infection and vaccination datasets. With the example of CoronaVac, we revealed the association between vaccine-induced immunological memory development and neutralizing antibody levels. The establishment of the intact immunological memory requires more than 6 months after the first and second doses, after that a booster shot can induce high levels neutralizing antibodies. By introducing the maximum viral load and recovery time after viral infection, we quantitatively studied the protective effect of vaccines against viral infection. Accordingly, we optimized the vaccination regimen, including dose and vaccination timing, and predicted the effect of the fourth dose. Last, by combining the viral transmission model, we showed the suppression of virus transmission by vaccination, which may be instructive for the development of public health policies.

q-bio.QM↗

arXiv2021

Model-based cellular kinetic analysis of SARS-CoV-2 infection: different immune response modes and treatment strategies

Increasing number in global COVID-19 cases demands for mathematical model to analyze the interaction between the virus dynamics and the response of innate and adaptive immunity. Here, based on the assumption of a weak and delayed response of the innate and adaptive immunity in SARS-CoV-2 infection, we constructed a mathematical model to describe the dynamic processes of immune system. Integrating theoretical results with clinical COVID-19 patients' data, we classified the COVID-19 development processes into three typical modes of immune responses, correlated with the clinical classification of mild & moderate, severe and critical patients. We found that the immune efficacy (the ability of host to clear virus and kill infected cells) and the lymphocyte supply (the abundance and pool of naïve T and B cell) play important roles in the dynamic process and determine the clinical outcome, especially for the severe and critical patients. Furthermore, we put forward possible treatment strategies for the three typical modes of immune response. We hope our results can help to understand the dynamical mechanism of the immune response against SARS-CoV-2 infection, and to be useful for the treatment strategies and vaccine design.

q-bio.PE↗