The Biology of Stem Cells in the Human Parasite Schistosoma Mansoni
人类寄生虫曼氏血吸虫干细胞的生物学
基本信息
- 批准号:9121333
- 负责人:
- 金额:$ 40.43万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-02-01 至 2021-01-31
- 项目状态:已结题
- 来源:
- 关键词:AblationAddressAdultAffectBiological ProcessBiologyBloodCellsCharacteristicsChronicDataDevelopmentDiseaseElectron MicroscopyEmployee StrikesEnsureEnvironmentFoundationsGene ExpressionGenesHomeostasisHumanImmuneImmune systemImmunityIn Situ HybridizationIntestinesKnowledgeLifeLinkLongevityMaintenanceMalariaMethodologyMolecularMolecular AnalysisMorphologyMusMuscle CellsNatural regenerationOrganismParasitesParasitic DiseasesPathologyPharmaceutical PreparationsPlatyhelminthsPluripotent Stem CellsPopulationPovertyPraziquantelProcessPropertyPublic HealthRNA InterferenceResearchRoleSchistosomaSchistosoma mansoniSchistosomiasisStem cellsStreamTestingTissuesTransplantationbasecell behaviorcombateggin vivoinnovationinsightneglected tropical diseasesnovelnovel therapeutic interventionnovel therapeuticspathogenprogramspublic health relevanceresearch studyresponsestem cell biologysurface coating
项目摘要
DESCRIPTION (provided by applicant): Schistosomiasis is a neglected tropical disease that affects more than 200 million people in the developing world. Currently only a single drug (praziquantel) is available to treat this disease, highlighting the importance of studies aimed at understanding basic biological processes in these organisms. One remarkable characteristic of schistosomiasis is that the parasites responsible for this disease (i.e., schistosomes) can live in
the blood stream of their human hosts for decades. How these parasites thrive in this immunologically hostile environment is not known. To address the longevity of these parasites in their mammalian host we previously demonstrated that schistosomes possess a population of somatic stem cells, which we refer to as neoblasts, which are capable of generating new intestine and muscle cells. Our preliminary studies for this proposal led us to a striking observation: a large fraction of these neoblasts differentiate to produce parts of the parasite's surface coat, a syncytial tissue known as the tegument. Our data suggest that tegumental cells are rapidly turned over, relying on neoblasts for their continuous renewal. As a result, many tegument-associated molecules are drastically down regulated within days following stem cell depletion. Since the tegument is the primary interface between the parasite and its host, understanding the stem cell-tegument relationship will provide important clues about how schistosomes defend themselves from immune attack. Based on these observations, we hypothesize that an important function of the neoblasts is to rapidly regenerate the parasite's tegument, thereby ensuring a functional host-parasite interface and evasion of host immunity. To address this hypothesis we propose the following two specific aims: (1) discover regulators of the neoblast-to-tegument transition and (2) understand the role for neoblasts in maintaining tegumental function in vivo. In the first aim, we will use transcriptional profiling and in situ hybridization to identify genes expressed in schistosome stem cells. We will then use RNA interference to determine which of these genes are required for the differentiation of the neoblasts into tegumental cells. In the second aim, we will use a combination of electron microscopy and immunological approaches to determine the effects that neoblast ablation has on tegumental morphology and function. Concurrently, we will surgically-transplant parasites incapable of making new tegumental cells into mice and examine the effects on worm survival. These studies are innovative as they are the first to explore the function of the neoblasts in the biology of this devastating parasite and bring a number of new methodologies to the table for studying these organisms. Collectively, these studies will determine how neoblasts contribute to parasite survival in the context of the host immune system, potentially leading to new therapeutic approaches targeting these important pathogens.
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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James J Collins其他文献
Comparative Analysis of Cas9 Activators Across Multiple Species
多个物种 Cas9 激活剂的比较分析
- DOI:
- 发表时间:
2016 - 期刊:
- 影响因子:0
- 作者:
Alejandro Chavez;Marcelle Tuttle;Benjamin W Pruitt;Ben Ewen;Raj;Chari;Dmitry Ter;Sabina J. Haque;Ryan J. Cecchi;Emma J K Kowal;Joanna Buchthal;B. Housden;N. Perrimon;James J Collins;George Church - 通讯作者:
George Church
Insulating gene circuits from context by RNA processing
通过 RNA 加工使基因回路与环境绝缘
- DOI:
10.1038/nbt.2411 - 发表时间:
2012-11-08 - 期刊:
- 影响因子:41.700
- 作者:
Caleb J Bashor;James J Collins - 通讯作者:
James J Collins
RNA synthetic biology
RNA 合成生物学
- DOI:
10.1038/nbt1208 - 发表时间:
2006-05-05 - 期刊:
- 影响因子:41.700
- 作者:
Farren J Isaacs;Daniel J Dwyer;James J Collins - 通讯作者:
James J Collins
Machine learning for synthetic gene circuit engineering
用于合成基因电路工程的机器学习
- DOI:
10.1016/j.copbio.2025.103263 - 发表时间:
2025-04-01 - 期刊:
- 影响因子:7.000
- 作者:
Sebastian Palacios;James J Collins;Domitilla Del Vecchio - 通讯作者:
Domitilla Del Vecchio
James J Collins的其他文献
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{{ truncateString('James J Collins', 18)}}的其他基金
Drug Target Discovery, Validation, and Prioritization for Schistosomiasis
血吸虫病药物靶标的发现、验证和优先排序
- 批准号:
10584296 - 财政年份:2022
- 资助金额:
$ 40.43万 - 项目类别:
Characterizing sexual development of the human parasite Schistosoma mansoni
人类寄生虫曼氏血吸虫的性发育特征
- 批准号:
10207379 - 财政年份:2020
- 资助金额:
$ 40.43万 - 项目类别:
Characterizing sexual development of the human parasite Schistosoma mansoni
人类寄生虫曼氏血吸虫的性发育特征
- 批准号:
10441417 - 财政年份:2020
- 资助金额:
$ 40.43万 - 项目类别:
Characterizing sexual development of the human parasite Schistosoma mansoni
人类寄生虫曼氏血吸虫的性发育特征
- 批准号:
10652328 - 财政年份:2020
- 资助金额:
$ 40.43万 - 项目类别:
The Biology of Stem Cells in the Human Parasite Schistosoma Mansoni
人类寄生虫曼氏血吸虫干细胞的生物学
- 批准号:
9207424 - 财政年份:2016
- 资助金额:
$ 40.43万 - 项目类别:
The Biology of Stem Cells in the Human Parasite Schistosoma Mansoni
人类寄生虫曼氏血吸虫干细胞的生物学
- 批准号:
10210085 - 财政年份:2016
- 资助金额:
$ 40.43万 - 项目类别:
The Biology of Stem Cells in the Human Parasite Schistosoma Mansoni
人类寄生虫曼氏血吸虫干细胞的生物学
- 批准号:
10544522 - 财政年份:2016
- 资助金额:
$ 40.43万 - 项目类别:
The characterization of neuropeptides in the Planarian Schmidtea mediterranea
地中海涡虫中神经肽的表征
- 批准号:
7982539 - 财政年份:2009
- 资助金额:
$ 40.43万 - 项目类别:
The characterization of neuropeptides in the Planarian Schmidtea mediterranea
地中海涡虫中神经肽的表征
- 批准号:
7750680 - 财政年份:2009
- 资助金额:
$ 40.43万 - 项目类别:
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