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

外体是从供体细胞释放出来并被受体细胞内化的小囊泡。这些小泡携带蛋白质、DNA和RNA。据认为，它们对细胞间的交流很重要，可能对疾病的发展也很重要。一些病毒会使用外显子来传播感染。在其他情况下，来自病毒感染细胞的外切体可以触发抗病毒反应，以帮助对抗病毒感染。腺病毒是一种导致普通感冒的病毒。这项建议的目的是通过比较体外未感染和感染细胞中外切体的形成，来检验腺病毒感染如何改变外切体的形成和组成。此外，还将开展工作，询问外切体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和病毒之间的相互作用提供新的信息，并将有助于更好地理解外切体的生物发生和病毒感染。这促进了美国国家科学基金会的任务，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NSF支持教育和科学多样性的使命。Exosome信号通路可能是病毒的另一条进入途径，也是病毒促进感染和致病的另一种机制。这些拟议的研究将评估普通感冒病毒，腺病毒，如何通过细胞培养条件下和动物体内的外切体生物发生和组成影响宿主器官。这项提案将侧重于澄清腺病毒和外切体之间的相互作用。有超过56种腺病毒血清型感染各种脊椎动物和无脊椎动物，使腺病毒成为这个项目的一个很好的病毒模型。这项提议将检验这一假设，即外切体的生物发生、组成和运输被外部因素/刺激(如病毒感染)改变，从而导致外切体的生物发生、组成、运输和细胞摄取的改变。1)评价病毒感染对外切体生物发生的影响，2)评价病毒感染对外切体组成的影响，3)评价外切体对腺病毒体外感染的影响，4)评价病毒感染对外切体生物发生的影响。这一建议具有很高的学术价值；拟议的研究可以极大地促进病毒学和外显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来开发和维持阿拉巴马州立大学的新研究计划，以及2)在STEM领域培训未被充分代表的本科生和研究生。该项目由整合组织系统(IOS)共生和自卫(SDS)计划、已建立的激发竞争力研究计划(EPSCoR)联合资助，历史黑人学院和大学本科项目(HBCU-UP)和历史黑人学院和大学卓越研究(HBCU-EIR)项目。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.