权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Molecular mechanisms of Plasmodium fertilization

疟原虫受精的分子机制

基本信息

批准号：
10064068
负责人：
MARCELO JACOBS-LORENA
金额：
$ 40.94万
依托单位：
JOHNS HOPKINS UNIVERSITY
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：
2016-12-07 至 2022-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10064068
关键词：
Affinity Antibodies Antibody Formation Binding Biological Assay Biology Biotin Blood Cell Separation Communicable Diseases Culicidae Development Disease Economics Enzyme-Linked Immunosorbent Assay Event Female Fertilization Genes Germ Cells Goals Human Immunofluorescence Immunologic In Vitro Intervention Knock-out Knowledge Laboratories Lead Libraries Life Cycle Stages Ligands Light Liver Malaria Mass Spectrum Analysis Membrane Proteins Midgut Molecular Molecular and Cellular Biology Nature Organism Parasites Parasitic Diseases Peptide Phage Display Library Peptide antibodies Peptides Persons Phage Display Plasmodium Play Population Process Proteins Proteome Receptor Gene Recombinants Refractory Research Role Salivary Glands Sexual Development Sexual Reproduction Structure Surface Surface Plasmon Resonance Tertiary Protein Structure Testing Transgenic Organisms Western Blotting base experimental study in vivo insight malaria transmission male novel parasite invasion peptide structure peptidomimetics prevent receptor receptor function sex tool transmission process transmission-blocking vaccine vector mosquito

项目摘要

ABSTRACT Malaria remains one of the most devastating infectious diseases. It kills over a million people every year while causing immense suffering and economic losses worldwide. Whereas much progress has been made in understanding the life cycle of the parasite in the human host and in the mosquito vector, significant gaps of knowledge remain. Fertilization of malaria parasites is a poorly understood process that takes place in the lumen of the mosquito gut. This process is important because survival in nature is completely dependent on the ability of the parasite to undergo sexual reproduction. The proposed research aims to identify molecular interactions that take place during fertilization of malaria parasites. This project is based on an unorthodox approach (identification of peptides that bind to the gamete surface) made possible by the recent development of an important tool, a transgenic parasite that produces red-fluorescent female gametes and green-fluorescent male gametes. Pure populations of malaria female and male gametes from this transgenic parasite were isolated by cell sorting and then used to screen a phage display library for peptides that recognize molecules on the gamete surfaces. A peptide (FG1) that binds to female gametes and another peptide (MG1) that binds to male gametes were identified. Importantly, when added to a malaria infectious blood meal, each of these peptides blocked parasite fertilization, suggesting that the peptides bound to a receptor and prevented its interaction with a ligand on the gamete of the opposite sex. Our working hypothesis is that the peptide structurally mimics the gamete ligand and that peptide and ligand compete for binding to the corresponding receptor. This proposal lays out a research plan to identify the receptor to which the FG1 and MG1 peptides bind and the ligands on the gametes of the opposite sex that the two peptides structurally mimic. An additional aim is to characterize the proteome on the surface of female gametes before and after fertilization, to gain insights on additional proteins involved in fertilization and possible block to polyspermy. Elucidation of mechanisms of fertilization is important not only for understanding the basic biology of malaria and other parasitic diseases but could also lead to the identification of new targets for blocking transmission and the spread of disease. Moreover, should the mechanisms be conserved, our findings could be extended to the biology of fertilization of higher organisms.

摘要

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Plasmodium female gamete surface HSP90 is a key determinant for fertilization.

疟原虫雌配子表面 HSP90 是受精的关键决定因素。

DOI：
10.1128/mbio.03142-23
发表时间：
2024
期刊：
mBio
影响因子：
6.4
作者：
Cha,Sung-Jae;Vega-Rodriguez,Joel;Tao,Dingyin;Kudyba,HeatherM;Hanner,Kelly;Jacobs-Lorena,Marcelo
通讯作者：
Jacobs-Lorena,Marcelo