Marsupial Immunobiology

大多数新生动物极易受到病原体和传染病的攻击。为了应对这些威胁，已经形成了为新生儿提供保护的母性因素的机制。对于有袋类哺乳动物来说尤其如此，比如负鼠和袋鼠，它们的幼崽出生时比人类或其他胎盘哺乳动物更不成熟。与胎盘哺乳动物相比，胎盘哺乳动物出生时免疫系统就相当发达，而有袋动物直到出生后才发育出免疫系统。该项目的目的是研究是否有袋动物免疫系统的新机制已经进化到保护新生儿。该项目将重点放在一种叫做B淋巴细胞的细胞群上，B细胞是产生抗体的细胞，并利用了一种有袋类动物的模型——灰短尾负鼠，它最近完成了完整的基因组测序，这是第一个有袋类动物的基因组测序。与来自母亲的抗体穿过胎盘的人类不同，负鼠新生儿出生时缺乏母亲的抗体，直到9天大时才发育成熟的B细胞。该项目的目标是利用细胞和分子技术来研究母亲通过母乳提供的抗体的多样性，以及新生儿体内产生B细胞的抗体的时间、位置和多样性。这个项目将提供对哺乳动物早期免疫保护策略的更好理解。该项目还将增加对有袋类动物免疫系统的现有知识，可用于模拟胎儿和早期新生儿的发育，也可用于癌症和传染病的模型。该项目将涉及研究生和本科生，并为博士后提供指导本科生的经验。除了直接的研究经验外，包括本科生在内的所有层次的学生都将参与出版，在国内和国际会议上发表演讲，并与国内和国际同事合作，后者主要在澳大利亚。本项目概述的工作将与正在进行的有袋动物比较基因组分析相结合，这样，将有助于更大的比较基因组工作，并对NSF生命之树倡议具有重要意义。

Most newborn animals are highly vulnerable to assault from pathogens and infectious diseases. In response to these threats mechanisms have evolved to provide the newborn with maternal factors for protection. This is particularly true for marsupial mammals, such as opossums and kangaroos, whose young are born less mature than that of humans or other placental mammals. In contrast to placental mammals that are born with a fairly developed immune system, marsupials do not develop their immune system until after they are born. The goal of this project is to investigate whether novel mechanisms in the marsupial immune system have evolved to protect the newborn. The project focuses on a population of cells called B lymphocytes, or B cells, which are the cells that make antibodies, and utilizes a model marsupial species, the gray short-tailed opossum, which recently had its complete genome sequenced, the first for a marsupial. In contrast to humans where antibodies from the mother cross the placenta, opossum newborns are born lacking maternal antibodies and do not develop mature B cells until they are nine days old. The goals of the project are to use cellular and molecular techniques to investigate the diversity of antibodies provided by the mother via the milk and the timing, location and diversity of antibody producing B cell development in the newborn. This project will provide a better understanding of strategies used in early immune protection in mammals. This project will also increase the available knowledge of the immune system of a marsupial species that can be used to model fetal and early newborn development and is also used as a model of cancer and infectious disease. This project will involve both graduate and undergraduate students and provide the opportunity for a postdoctoral fellow to gain experience mentoring undergraduate students. In addition to direct research experience, students at all levels, including undergraduate, will participate in publications, presentations at national and international meetings, and the collaborations with domestic and international colleagues, the latter primarily in Australia. The work outlined in this project will be integrated with ongoing comparative genomic analyses with marsupials and, in that way, will contribute to the larger comparative genomic efforts and has significance for the NSF Tree of Life Initiative.