Multiscale modeling of the battle over iron in invasive lung infection

侵袭性肺部感染中铁之争的多尺度建模

基本信息

批准号：
10441249
负责人：
REINHARD LAUBENBACHER
金额：
$ 73.99万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-08 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10441249
关键词：
3-Dimensional Address Animal Model Antifungal Agents Aspergillosis Aspergillus Aspergillus fumigatus Biological Cells Cessation of life Communities Complex Data Development Disease Environment Epithelial Event Feedback Goals Health Heme Heme Iron Hemorrhage Homeostasis Hormones Host Defense Human Hybrids Immune response Immunity Immunocompromised Host Immunology Impairment In Vitro Individual Infection Inhalation Innate Immune Response Intervention Iron Laboratories Lead Leukocytes Life Liver Lung Lung infections Malignant Neoplasms Mathematics Modeling Molecular Mycoses Organ Organism Outcome Pharmaceutical Preparations Population Process Production Reproducibility Reproduction spores Research Personnel Resistance Resources Respiratory Tract Infections Role Scientist Signal Transduction Software Design System Technology Therapeutic Therapeutic immunosuppression Time Tissues Transplantation antimicrobial cell type computerized tools experimental study flexibility fungus improved in silico in vivo innovation iron metabolism mathematical model microorganism molecular modeling molecular scale monocyte mouse model multi-scale modeling network models neutrophil novel novel therapeutics open source pathogen response simulation therapeutic target tool trend

项目摘要

PROJECT SUMMARY Invasive aspergillosis is among the most common fungal infection in immunocompromised hosts and carries a poor outcome. The spores of the causative organism, Aspergillus fumigatus, are ubiquitously distributed in the environment. Healthy hosts clear the inhaled spores without developing disease, but individuals with impaired immunity are susceptible to a life-threatening respiratory infection that can then disseminate to other organs. The increasing use of immunosuppressive therapies in transplantation and cancer has dramatically increased suffering and death from this infection, and this trend is expected to continue. Current therapeutic approaches have been focused primarily on the pathogen, but a better understanding of the components of host defense in this infection may lead to the development of new treatments against this infection, possibly in combination with antifungal drugs. Iron is essential to all living organisms, and restricting iron availability is a critical mechanism of antimicrobial host defense against many microorganisms; conversely, successful pathogens have evolved potent mechanisms for scavenging iron from the host. These mechanisms have the potential to be harnessed therapeutically, for example with drugs that enhance the host’s iron sequestration mechanisms. The overarching goal of this project is to develop a multi-scale mathematical model that can serve as a simulation tool of the role of iron in invasive aspergillosis. The model will integrate mechanisms at the molecular scale with tissue-level events and a whole-body scale capturing the role of the liver. The project brings an innovative approach to the study of this infection, and introduces innovative features to multiscale modeling through a novel modular software design that improves flexibility, reproducibility, and model sharing.

项目摘要浸润性曲霉病是免疫功能低下的宿主中最常见的真菌感染之一，并带有A 结果不佳。致病生物的孢子，曲霉的烟曲霉，无处不在地分布在环境。健康的宿主清除了遗传的孢子而没有发展疾病，但患有受损的人免疫力容易受到威胁生命的呼吸道感染，然后可以传播到其他器官。免疫抑制疗法在移植和癌症中的越来越多增加了这种感染的痛苦和死亡，预计这种趋势将继续。当前的治疗方法主要专注于病原体，但对宿主防御组成部分的理解是这种感染可能导致针对这种感染的新疗法发展，可能结合抗真菌药物。铁对于所有生物生物都是必不可少的，限制铁的可用性是抗菌宿主防御许多微生物；相反，成功的病原体发展了从宿主那里清除铁的有效机制。这些机制有可能利用在治疗上，例如使用可以增强宿主铁隔离机制的药物。该项目的总体目标是开发一个可以用作模拟的多尺度数学模型铁在浸润性曲霉病中的作用工具。该模型将以分子尺度整合机制随着组织水平事件和全身量表捕捉肝脏的作用。该项目带来了创新的研究这种感染的方法，并通过一个新颖的模块化软件设计，可提高灵活性，可重复性和模型共享。

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The natural killer cell activating receptor, NKG2D, is critical to antibody-dependent chronic rejection in heart transplantation.

DOI：
10.1111/ajt.16690
发表时间：
2021-11
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
0
作者：
通讯作者：

Cyclophosphamide for the treatment of Acute Exacerbation of Interstitial Lung Disease: A Review of the Literature.

DOI：
10.36141/svdld.v38i1.11271
发表时间：
2021
期刊：
Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG
影响因子：
0
作者：
Innabi A;Gomez-Manjarres D;Alzghoul BN;Chizinga M;Mehrad B;Patel DC
通讯作者：
Patel DC

Lung transplantation for acute exacerbation of interstitial lung disease.

DOI：
10.1136/thoraxjnl-2020-215681
发表时间：
2022-04
期刊：
Thorax
影响因子：
10
作者：
Chizinga M;Machuca TN;Shahmohammadi A;Patel DC;Innabi A;Alzghoul B;Scheuble V;Pipkin M;Mehrad B;Pelaez A;Lin C;Gomez-Manjarres D
通讯作者：
Gomez-Manjarres D

The Role of Bronchoscopic Interventions in the Management of Pneumothorax in Interstitial Lung Disease.