Gut Epithelial Cell Receptors for C parvum Invasion

描述（由申请方提供）：微小隐孢子虫是一种胃肠道寄生虫，可在免疫功能低下的宿主中引起慢性、严重和经常致命的肠道疾病，目前尚无治疗方法。目前治疗这种寄生虫感染的治疗方法的发展策略集中在破坏子孢子附着和侵入肠上皮细胞的过程。这些研究已经确定了两个子孢子配体，gp 900和gp 40/15，其粘附于上皮细胞并介导附着和侵袭。编码这些糖蛋白的基因已被鉴定、克隆和表达，但功能性重组C。微小配体需要在真核系统中表达以产生对上皮细胞结合至关重要的特定碳水化合物表位。缺乏功能性重组C.细小病毒配体阻碍了对寄生虫用于侵入细胞的上皮细胞受体的鉴定。本项目的主要目标是分离和鉴定gp 900和gp 40/15的上皮细胞受体。本课题的具体目标是：具体目标1：制备重组gp 900糖蛋白，并在体外研究天然和重组gp 900与肠上皮细胞的结合;具体目标2：鉴定gp 900和gp 40/15的肠上皮细胞受体。微小孢子子孢子附着和侵入，并将推进隐孢子虫病治疗策略的发展目标。该奖项将为候选人奥康纳博士提供研究C.在分子水平上研究寄生虫配体与上皮细胞受体的相互作用，并为她在宿主-寄生虫相互作用领域建立独立的研究计划提供基础。奥康纳博士将由她的赞助商沃德博士提供咨询，沃德博士是一位胃肠病学家，也是公认的肠道寄生虫专家。她的共同导师Kopin博士具有识别和表征胃肠道受体的丰富经验。新英格兰医学中心与塔夫茨大学和更广泛的波士顿科学界合作，为研究人员提供多样化和优秀的科学资源，并为年轻科学家提供特殊的环境。

DESCRIPTION (provided by applicant):Cryptosporidium parvum is a gastrointestinal parasite that causes chronic, severe, and frequently fatal diarrheal disease in immunocompromised hosts, for which there is no treatment. Current strategies for the development of therapies to treat this parasitic infection have focused on disruption of the processes of sporozoite attachment and invasion into intestinal epithelial cells. These studies have identified two sporozoite ligands, gp900 and gp40/15, that adhere to epithelial cells and mediate attachment and invasion. The genes encoding these glycoproteins have been identified, cloned, and expressed, but production of functional recombinant C. parvum ligands requires expression in eukaryotic systems to generate the particular carbohydrate epitopes critical for epithelial cell binding. The lack of functional recombinant C. parvum ligands has hampered identification of the epithelial cell receptors used by the parasite to invade cells. The major goal of this project is to isolate and identify the epithelial cell receptors for gp900 and gp40/15. The specific aims of this project are:Specific Aim 1: To generate recombinant gp900 glycoproteins and characterize binding of native and recombinant gp900 to intestinal epithelial cells in vitro.Specific Aim 2: To identify intestinal epithelial cell receptors for gp900 and gp40/15Results from these experiments will provide greater insight into the processes of C. parvum sporozoite attachment and invasion and will advance the goal of developing treatment strategies for cryptosporidiosis. This award will provide the candidate, Dr. O'Connor, with the opportunity to study C. parvum ligand-epithelial cell receptor interactions at the molecular level, and provide the groundwork for her to establish an independent research program in the field of host-parasite interactions. Dr. O'Connor will be advised by her sponsor, Dr. Ward, a gastroenterologist and a recognized expert on enteric parasites. Her co-mentor, Dr. Kopin, has extensive experience identifying and characterizing gastrointestinal receptors. New England Medical Center, in association with Tufts University and the wider Boston scientific community provides researchers with diverse and excellent scientific resources, and is exceptional environment for a young scientist.