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• 批准号: 9262735
• 负责人: SHRIPAD D. TULJAPURKAR
• 金额: $ 10.04万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9262735
• 关键词: Administrator; Africa; Asia; Cells; Characteristics; Clinical; Clinical Research; Communication; Community Surveys; Computer software; Computers; Culicidae; Custom; Data; Data Collection; Data Quality; Databases; Dictionary; Disease; Dissection; Drug resistance; Drug usage; Ensure; Evolution; Experimental Designs; Genomics; Government; Human; Imagery; Immunity; India; Institutes; Laboratories; Laboratory Study; Lead; Maintenance; Malaria; Manuscripts; Medical Research; Morbidity - disease rate; Nature; Parasites; Pathology; Pathway interactions; Pattern; Phenotype; Plasmodium falciparum; Plasmodium vivax; Power Sources; Preparation; Procedures; Quality Control; Reporting; Research; Research Design; Resource Sharing; Resources; Sampling; Scientist; Security; Shapes; Site; Source; Statistical Data Interpretation; System; Time; Training; Universities; Variant; Washington; Work; base; clinical research site; data management; data sharing; human disease; human subject; interest; international center; member; mortality; novel; protocol development; response; statistics; trait; transmission process; urban area; vector; vector control; vector mosquito

Malaria is a devastating human disease, especially amongst the most vulnerable sub-populations of the world. It is important to understand how malaria parasites will respond to global elimination efforts. The emergence of drug resistance, dissemination of these traits to broader localities, and evolution of parasites into forms that may lead to greater pathology are of particular interest. The dominant human malaria parasite, P. falciparum, has been studied in Africa and SE Asia, but much remains to be learned about its patterns in South Asia. The other major human malaria parasite, P. vivax, continues to cause morbidity and mortality. However, phenotypic dissection of P. vivax traits and formal demonstration of variations between P. vivax isolates is restricted by our limited ability to culture them. In this renewal application, we will study: (1) the extent to which drug use and drug resistance shape the evolution of malaria parasites in India, (2) the extent to which vector distribution and characteristics effect transmission of drug resistance traits, and (3) how parasites’ response to immunity triggers novel interactions with host cells and leads to severe disease. India has both P. falciparum and P. vivax, has ecological conditions that are different and relevant, and may act as a bridge between SE Asia and eastern coast of E Africa. The MESA team partners will study malaria parasites in human hosts, mosquito vectors, and controlled laboratory studies after adaptation. Over the last five years, the team has successfully developed new clinical study sites in urban areas and community survey capabilities in remote, isolated parts of India. Our ability to work closely and collaboratively with government and non-governmental entities in India and provide professional opportunities for young, local scientists greatly facilitate our work. Key findings on evolution of drug resistance in malaria parasites, their interactions with mosquitoes, and ability to cause severe disease will be further pursed in this competitive renewal.

疟疾是一种毁灭性的人类疾病，特别是在最脆弱的亚人群中 重要的是要了解疟疾寄生虫将如何应对全球消除。 耐药性的出现、这些特征向更广泛的地区传播，以及 寄生虫进化成可能导致更大病理学的形式尤其令人感兴趣。 人类疟原虫的主要寄生虫恶性疟原虫已在非洲和东南亚进行了研究，但 关于南亚其他主要人类疟疾的模式还有很多有待了解。 然而，间日疟原虫继续导致发病和死亡。 间日疟原虫性状和间日疟原虫分离株之间变异的正式证明受到以下限制： 我们培养它们的能力有限。在这个更新申请中，我们将研究：（1）在多大程度上。 药物使用和耐药性影响了印度疟疾寄生虫的进化，(2) 哪些载体分布和特征影响耐药性状的传播，以及（3） 寄生虫对免疫的反应如何触发与宿主细胞的新相互作用并导致严重的 印度同时存在恶性疟原虫和间日疟原虫，生态条件不同。 且相关，并且可以充当东南亚和东非东海岸之间的桥梁。 团队合作伙伴将研究人类宿主、蚊子媒介和受控疟疾寄生虫 经过实验室研究，在过去的五年里，该团队已经成功开发出来。 城市地区的新临床研究地点和偏远地区的社区调查能力 我们与政府和非政府组织密切合作的能力。 印度的实体并为年轻的当地科学家提供专业机会极大地促进了 我们的工作有关疟原虫耐药性进化及其相互作用的主要发现。 蚊子以及引起严重疾病的能力将在这次竞争更新中得到进一步的追求。