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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.

项目摘要侵袭性曲霉病是免疫受损宿主中最常见的真菌感染之一，可怜的结果。病原体烟曲霉的孢子普遍分布在环境健康的宿主可以清除吸入的孢子而不发生疾病，但受损的个体免疫系统容易受到威胁生命的呼吸道感染，然后传播到其他器官。在移植和癌症中越来越多地使用免疫抑制疗法，这种感染造成的痛苦和死亡，预计这一趋势将继续下去。目前的治疗方法主要集中在病原体上，但更好地了解宿主防御的组成部分，这种感染可能会导致开发新的治疗方法来对抗这种感染，抗真菌药物。铁对所有生物体都是必不可少的，限制铁的可用性是铁缺乏的关键机制。抗微生物宿主防御许多微生物;相反，成功的病原体已经进化从宿主体内清除铁的有效机制这些机制有可能被利用在治疗上，例如用增强宿主的铁螯合机制的药物。的这个项目的首要目标是开发一个多尺度的数学模型，可以作为一个模拟铁在侵袭性曲霉病中的作用的工具。该模型将在分子尺度上整合机制其中组织水平事件和全身尺度捕获肝脏的作用。该项目带来了一个创新的的方法来研究这种感染，并介绍了创新的功能，多尺度建模，通过一个新颖的模块化软件设计，提高了灵活性、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.

天然杀伤细胞激活受体NKG2D对抗体依赖性慢性抑制至关重要。

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.