Excellence in Research: InnovAtive Methods and Advanced Science at Alabama State University (IAM-ASU)

外泌体是从供体细胞释放出来并被受体细胞内化的小泡。这些囊泡携带蛋白质、DNA和RNA。人们认为它们对细胞间的通讯很重要，并且可能对疾病的发展很重要。有些病毒会利用外泌体传播感染。在其他情况下，来自病毒感染细胞的外泌体可以触发抗病毒反应，帮助对抗病毒感染。腺病毒是一种引起普通感冒的病毒。本提案的目的是通过比较体外未感染和感染细胞的外泌体形成，研究腺病毒感染如何改变外泌体的形成和组成。此外，研究人员还将探讨外泌体的形成改变与腺病毒感染的严重程度之间是否存在联系。这些研究将为宿主细胞与病毒之间的相互作用提供新的信息，并将导致对外泌体生物发生和病毒感染的更好理解。这促进了NSF的使命，因为它促进了科学的进步。该项目还将支持本科生和研究生的教育。因此，它履行了美国国家科学基金会支持科学教育和多样性的使命。外泌体信号通路可能是病毒的另一种进入途径，也是病毒促进感染和发病的另一种机制。这些拟议的研究将评估普通感冒病毒，腺病毒如何在细胞培养条件和动物中通过外泌体的生物发生和组成影响宿主生物。这一建议将侧重于澄清腺病毒和外泌体之间的相互作用。有超过56种腺病毒血清型感染多种脊椎动物和无脊椎动物物种，使腺病毒成为本项目的良好病毒模型。该提案将验证外泌体的生物发生、组成和运输被外部因素/刺激（如病毒感染）改变的假设，从而导致外泌体的生物发生、组成、运输和细胞摄取发生改变。实现目的的目的是：1)评估病毒感染对外泌体生物发生的体外影响，2)评估病毒感染对外泌体组成的体外影响，3)评估外泌体对体外腺病毒感染的影响，4)评估病毒感染对外泌体生物发生的体内影响。这个建议有很高的智力价值；该研究将显著促进病毒学和外泌体生物学领域的科学知识。这项研究的更广泛的影响包括：1)直接定位首席研究员在阿拉巴马州立大学开发和维持一个新的研究项目；2)在STEM领域培训代表性不足的本科生和研究生。该项目由综合有机体系统（IOS）共生和自卫（SDS）计划、刺激竞争研究的既定计划（EPSCoR）、历史上的黑人学院和大学本科计划（HBCU-UP）和历史上的黑人学院和大学卓越研究（HBCU-EiR）计划共同资助。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Exosomes are small vesicles that are released from donor cells and internalized by a recipient cell. These vesicles carry proteins, DNA and RNA. It is thought that they are important for cell-to-cell communication, and may be important for development of disease. Some viruses will use exosomes to spread infections. In other cases, exosomes from virus-infected cells can trigger anti-viral responses to help combat virus infections. Adenovirus is a virus that causes the common cold. The goal of this proposal is to examine how adenovirus infection alters the formation and composition of exosomes by comparing exosome formation in uninfected and infected cells in vitro. In addition, work will be performed to ask if there is a connection between altered exosome formation and severity of adenovirus infection. These studies will provide new information on the interaction between the host cell and viruses, and will lead to a greater understanding of exosome biogenesis and virus infections. This promotes the NSF mission because it promotes the progress of science. This project will also support the education of undergraduate and graduate students. Therefore, it fulfills the mission of the NSF to support education and diversity in science.Exosome signaling pathways are likely to be an additional entry pathway for viruses as well as an additional mechanism by which viruses promote infection and pathogenesis. These proposed studies will evaluate how the common cold virus, adenovirus, affects the host organism via exosome biogenesis and composition in cell culture conditions and in animals. This proposal will focus on clarifying interactions between adenoviruses and exosomes. There are over 56 adenovirus serotypes infecting a variety of vertebrate and invertebrate species, making adenovirus a good virus model for this project. This proposal will test the hypothesis that exosome biogenesis, composition, and trafficking are altered by external factors/stimuli such as viral infections, thus leading to altered exosome biogenesis, composition, trafficking, and cellular uptake. The objectives to achieve the goal are: 1) to evaluate the in vitro impact of virus infection on exosome biogenesis, 2) to evaluate the in vitro impact of virus infection on exosome composition, 3) to evaluate the impact of exosomes on in vitro adenovirus infection, 4) to evaluate the in vivo impact of virus infection on exosome biogenesis. This proposal has high intellectual merit; the proposed research could significantly advance scientific knowledge in the field of virology and exosome biology. Broader impacts of this study include: 1) directly positioning the principal investigator to develop and sustain a new research program at Alabama State University and 2) training of under-represented undergraduate and graduate students in STEM fields.This project is jointly funded by the Integrative Organismal Systems (IOS) Symbiosis and Self-Defense (SDS) program, the Established Program to Stimulate Competititve Research (EPSCoR),the Historically Black Colleges and Universities Undergraduate Program (HBCU-UP) and Historically Black Colleges and Universities Excellence in Research (HBCU-EiR) programs.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.