Mathematical Modeling Core

数学建模核心

• 批准号: 10599359
• 负责人: ALAN S PERELSON
• 金额: $ 34.89万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10599359
• 关键词: Address; Adverse drug effect; Affect; Aftercare; Bioinformatics; Biological Assay; Blood; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; Cells; Collaborations; DNA; Data; Data Analyses; Data Set; Development; Drops; Event; Experimental Designs; Fostering; Generations; Goals; HIV; HIV Infections; HIV-1; Immune response; Immune system; Individual; Infection; Infection Control; Kinetics; Laboratories; Length; Measures; Mission; Modeling; Mutation; Natural Killer Cells; Persons; Phase; Plasma; Population; Process; Property; Proviruses; Public Health; Research; Research Project Grants; Research Support; Rest; SIV; Sampling; Shapes; System; T-Cell Depletion; Techniques; Testing; Time; Tissues; Viral; Viremia; Virus; antiretroviral therapy; computing resources; data integration; dynamic system; experimental analysis; innovation; insight; latent HIV reservoir; mathematical model; member; nonhuman primate; novel; predictive modeling; programs; response; simulation; synergism; viral rebound

Summary – Mathematical Modeling Core HIV infection remains an important public health problem. Effective antiretroviral therapy (ART) can control the infection, but lifelong ART is challenging and is encumbered by long-term adverse drug effects. The major challenge to eradicating HIV-1 is the existence of the long-lived latent HIV-1 resevoir. While reservoir eradication is the ultimate goal, to achieve that goal we need greater understanding of the factors underlying the establishment of the reservoir, the composition of the reservoir, the dynamics of the reservoir and if there are specific properties of reservoir cells that could be exploited to enhance their elimination. Following the initiation of ART, the amount of virus in the blood drops dramatically. This is due to the fact that most infected cells die very quickly, and when new infection events are blocked by ART, this decay becomes apparent. However, not all of the infected cells die; some survive and may become part of the stable latent reservoir. This research program will study these decay processes using precise quantitative assays and single cell techniques in hope of understanding whether the decay represents a selection process that shapes the composition of the latent reservoir. The Modeling Core will develop mathematical models to explain these decay processes and how they are related to the dynamics of the latent reservoir. The Core will also provide expertise in experimental design and analysis of experimental results. We hope that this collaborative, quantitative approach will lead to a better understanding of how the reservoir forms and persists and to novel cure strategies.

总结 - 数学建模核心 HIV 感染仍然是一个重要的公共卫生问题。 控制感染，但终身抗逆转录病毒疗法具有挑战性，并受到长期不良药物的阻碍 根除 HIV-1 的主要挑战是长期潜伏 HIV-1 病毒库的存在。 虽然消灭水库是最终目标，但为了实现这一目标，我们需要更深入地了解 水库形成的因素、水库的组成、动态 储库细胞是否具有可用于增强储库细胞的特定属性 开始抗逆转录病毒疗法后，血液中的病毒数量急剧下降。 这是因为大多数受感染的细胞很快就会死亡，当新的感染事件发生时 被 ART 阻断后，这种衰变变得明显，但并非所有受感染的细胞都会死亡；有些细胞会存活下来。 并可能成为稳定的潜在储存库的一部分，该研究计划将研究这些衰变。 使用精确定量测定和单细胞技术的过程，希望能够理解 衰变是否代表了塑造潜在储库成分的选择过程。 建模核心将开发数学模型来解释这些衰变过程以及它们如何 与潜在储层动力学相关的核心还将提供实验方面的专业知识。 我们希望这种协作、定量的方法能够设计和分析实验结果。 有助于更好地了解水库如何形成和持续存在，并制定新的治疗策略。