Mechanisms of Infection Chronicity and Pathogenesis in Gastrointestinal Chagas disease

胃肠道恰加斯病的感染慢性机制和发病机制

基本信息

项目摘要

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. Chagas is a neglected tropical disease that affects millions of people from Latin America. Infected people carry the parasite for life but many never experience any symptoms. Others develop serious problems affecting the heart and/or the digestive tract. The reasons why people progress to different types of disease is not well understood. During chronic infections, only small numbers of parasites are present and they are located inside cells, within solid tissue. This has made it difficult to detect parasites and investigate their contribution to the disease process. We developed a technique that makes these experiments much easier. It is based on transgenic T. cruzi parasites that have been engineered to express a light-emitting enzyme. By measuring the intensity of light emitted by the parasites we can track and quantify them inside live mice and in specific organs. We have already applied this system to study the development of Chagas heart disease and to test whether drugs can cure T. cruzi infections in mice. In this project we will now apply this technology to investigate the digestive form of Chagas disease. First we will find out which parts of the mouse's digestive tract are affected by T. cruzi infection and ask whether parasites or mice with different genetics are associated with different levels of disease severity. Next we will analyse the microscopic changes that affect the gut's muscles and the parts of the nervous system that control them. We will also investigate how the mouse's immune system responds to T. cruzi, and find out if these responses play a part in the development of disease. Finally, we will test whether benznidazole, a drug that can cure mice of T. cruzi infection, can also prevent the development and progression of digestive pathology. Together these studies will provide a much better understanding of how T. cruzi causes chronic infections and leads to symptomatic Chagas disease affecting the GI tract. This will help accelerate the development of novel strategies to treat patients.
查加斯病是由原生动物寄生虫克氏锥虫引起的。恰加斯病是一种被忽视的热带疾病,影响着拉丁美洲数百万人。感染者终生携带寄生虫,但许多人从未出现任何症状。其他人会出现严重的问题,影响心脏和/或消化道。人们发展为不同类型疾病的原因还不清楚。在慢性感染期间,只有少量的寄生虫存在,它们位于细胞内,固体组织内。这使得检测寄生虫和调查它们对疾病过程的贡献变得困难。我们开发了一种技术,使这些实验更容易。它是基于转基因T.这些克氏寄生虫被改造成能表达发光酶。通过测量寄生虫发出的光的强度,我们可以在活小鼠和特定器官中跟踪和量化它们。我们已经应用这个系统来研究查加斯心脏病的发展,并测试药物是否能治愈查加斯心脏病。小鼠的Cruzi感染。在这个项目中,我们现在将应用这项技术来研究恰加斯病的消化形式。首先,我们将找出老鼠消化道的哪些部分受到T。克氏感染,并询问是否寄生虫或不同遗传的小鼠与不同程度的疾病严重程度有关。接下来,我们将分析影响肠道肌肉和控制它们的神经系统部分的微观变化。我们还将研究小鼠的免疫系统如何对T。cruzi,并找出这些反应是否在疾病的发展中发挥作用。最后,我们将测试是否苄硝唑,一种药物,可以治愈小鼠的T。克氏感染,也可以防止消化道病理的发展和进展。总之,这些研究将提供一个更好地了解T。cruzi引起慢性感染并导致影响胃肠道的有症状的查加斯病。这将有助于加速开发治疗患者的新策略。

项目成果

期刊论文数量(10)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Local association of Trypanosoma cruzi chronic infection foci and enteric neuropathic lesions at the tissue micro-domain scale
组织微域尺度上克氏锥虫慢性感染病灶与肠神经病变的局部关联
  • DOI:
    10.1101/2021.03.09.434577
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Khan A
  • 通讯作者:
    Khan A
Drug-cured experimental Trypanosoma cruzi infections confer long-lasting and cross-strain protection.
药物治愈的实验性克氏锥虫感染可提供持久的跨菌株保护。
Local association of Trypanosoma cruzi chronic infection foci and enteric neuropathic lesions at the tissue micro-domain scale.
  • DOI:
    10.1371/journal.ppat.1009864
  • 发表时间:
    2021-08
  • 期刊:
  • 影响因子:
    6.7
  • 作者:
    Khan AA;Langston HC;Costa FC;Olmo F;Taylor MC;McCann CJ;Kelly JM;Lewis MD
  • 通讯作者:
    Lewis MD
Fatal progression of experimental visceral leishmaniasis is associated with intestinal parasitism and secondary infection by commensal bacteria, and is delayed by antibiotic prophylaxis
  • DOI:
    10.1371/journal.ppat.1008456
  • 发表时间:
    2020-04-01
  • 期刊:
  • 影响因子:
    6.7
  • 作者:
    Lewis, Michael D.;Paun, Andrea;Sacks, David L.
  • 通讯作者:
    Sacks, David L.
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Michael Lewis其他文献

Sentiment analysis of Artificial Advisors in Search and Rescue Tasks
搜索救援任务中人工顾问的情感分析
Digital Humanities Solutions for pan-European Numismatic and Archaeological Heritage Based on Linked Open Data
基于关联开放数据的泛欧洲钱币和考古遗产数字人文解决方案
  • DOI:
  • 发表时间:
    2022
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Eljas Oksanen;Heikki Rantala;J. Tuominen;Michael Lewis;D. Wigg;Frida Ehrnsten;E. Hyvönen
  • 通讯作者:
    E. Hyvönen
Interactive simulation of the NIST USAR arenas
NIST USAR 竞技场的交互式模拟
Collision handling in virtual environments; facilitating natural user motion
虚拟环境中的碰撞处理;
Combinatory Categorial Grammars for Robust Natural Language Processing
用于鲁棒自然语言处理的组合范畴语法
  • DOI:
  • 发表时间:
    2012
  • 期刊:
  • 影响因子:
    0
  • 作者:
    M. Steedman;S. Clark;J. Curran;J. Hockenmaier;T. Kwiatkowski;Michael Lewis;P. Boonkwan;Greg Copolla;S. Goldwater;Luke Zettlemoyer
  • 通讯作者:
    Luke Zettlemoyer

Michael Lewis的其他文献

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{{ truncateString('Michael Lewis', 18)}}的其他基金

Breaking Risk Habituation to Occupational Hazards using Virtual Reality Interventions with Aversive Sensory Feedback
使用虚拟现实干预措施和令人厌恶的感官反馈来打破对职业危害的风险习惯
  • 批准号:
    2017019
  • 财政年份:
    2020
  • 资助金额:
    $ 68.46万
  • 项目类别:
    Standard Grant
Collaborative Research: Multiscale Modeling of Mammary Gland Development
合作研究:乳腺发育的多尺度建模
  • 批准号:
    1263751
  • 财政年份:
    2013
  • 资助金额:
    $ 68.46万
  • 项目类别:
    Standard Grant
CPS: Synergy: Collaborative Research: Formal Models of Human Control and Interaction with Cyber-Physical Systems
CPS:协同:协作研究:人类控制和与网络物理系统交互的形式模型
  • 批准号:
    1329762
  • 财政年份:
    2013
  • 资助金额:
    $ 68.46万
  • 项目类别:
    Standard Grant
Collaborative Research: Social Movements and Policy Impact
合作研究:社会运动和政策影响
  • 批准号:
    1247321
  • 财政年份:
    2012
  • 资助金额:
    $ 68.46万
  • 项目类别:
    Standard Grant
II-EN: Infrastructure for Computer Systems Research
II-EN:计算机系统研究基础设施
  • 批准号:
    0958501
  • 财政年份:
    2010
  • 资助金额:
    $ 68.46万
  • 项目类别:
    Standard Grant
REU SITE: Computer Systems Research in High Performance Cloud Computing Environments
REU 站点:高性能云计算环境中的计算机系统研究
  • 批准号:
    1005153
  • 财政年份:
    2010
  • 资助金额:
    $ 68.46万
  • 项目类别:
    Standard Grant
SBIR Phase I: TriStar, An Algebraic High Performance Communications Signal Processor
SBIR 第一阶段:TriStar,代数高性能通信信号处理器
  • 批准号:
    0945722
  • 财政年份:
    2010
  • 资助金额:
    $ 68.46万
  • 项目类别:
    Standard Grant
REU Sites: Experimental Computer Systems Research at Binghamton University
REU 站点:宾厄姆顿大学实验计算机系统研究
  • 批准号:
    0649252
  • 财政年份:
    2007
  • 资助金额:
    $ 68.46万
  • 项目类别:
    Standard Grant
Immortal Information & Through-life Knowledge Management (IITKM): Strategies & Tools for the Emerging Product-Service Paradigm
不朽信息
  • 批准号:
    EP/E502350/1
  • 财政年份:
    2006
  • 资助金额:
    $ 68.46万
  • 项目类别:
    Research Grant
CRI: Heterogeneous High Performance Infrastructure for Computer Systems Research
CRI:计算机系统研究的异构高性能基础设施
  • 批准号:
    0454298
  • 财政年份:
    2005
  • 资助金额:
    $ 68.46万
  • 项目类别:
    Continuing Grant

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