CAREER: A paired experimental-computational approach to elucidate stress responses in early-branching eukaryotes

细胞感知周围环境，并利用这些信息来适应压力环境。这些反应可以决定细胞是死亡还是存活，以根据新环境（即不同的温度、营养水平或化学成分）进行改变。这个项目将使用单细胞生物来更多地了解细胞如何应对压力。具体来说，疟原虫细胞在宿主细胞内外以及不同动物体内的生存环境非常广泛。这些细胞使用一些与多细胞动物相同的方法，但也有显著的差异。由于它们有能力从宿主那里获得所需的东西，许多寄生虫在进化过程中简化了它们的努力；因此，疟原虫的反应可能代表了在不同环境中生存所需的最小组成部分，并可能为其他单细胞生物如何适应压力提供见解。这项工作的更广泛影响包括内在研究，因为这种群体或有机体感染了广泛的宿主细胞，在那里它们可能导致疟疾等疾病。其他活动通过使用虚拟教育工具将研究与教育外展计划相结合，以准确和令人兴奋的方式描述及时的生物学主题，以提高公众素养。在全球大流行期间，这一点尤其重要，因为对疾病传播的基本了解可以大大提高对公共卫生准则的遵守程度，而高质量的远程学习可以减少学校关闭的影响。这项研究将有助于理解细胞机制，驱动适应和生存，以应对环境压力。这些反应对早期分支真核原生动物至关重要，如顶复合体，它们在复杂的生命周期中在各种环境中茁壮成长。由于顶复合体原生动物与高等真核生物的早期分化，以及细胞内寄生生活方式所提供的生理缓冲，它们被认为具有强大的应激反应所需的基本成分。疟原虫，顶复合体属之一，保留热休克反应和翻译抑制，但营养信号通路缺乏关键的同源物（即mTOR激酶）。该项目将支持跨物种比较计算工具的使用，并生成开放获取的多组学数据集和突变寄生虫系，供研究界使用。此外，通过强调在不同环境中生存所需的关键、基本能力，识别顶复合体应激反应与高等生物不同的方面将挑战应激反应领域的主流观点。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。

Cells sense their surroundings and use this information to adapt to stressful conditions. These responses can determine whether a cell dies or survives to change according to the new environment (i.e. different temperature, nutrient levels, or chemical makeup). This project will use a single cell organism to understand more about how cells respond to stress. Specifically, Plasmodium cells survive in a wide range of environments as they live inside or outside host cells and within different animals. These cells use some of the same approaches as multi-cellular animals, yet there are notable differences. Due to their ability to acquire what they need from their host, many parasites streamline their efforts as they evolve; therefore, Plasmodium responses may represent the minimal components required for survival in diverse environments and could provide insight into how other single cell organism adapt to stress. The Broader Impact of the work includes the intrinsic research as this group or organisms infects a wide range of host cells where they can cause such afflictions as malaria. Additional activities seek to improve public literacy by integrating research with an educational outreach program using virtual educational tools, which describe timely biological topics in an accurate and exciting way. This is particularly important during a global pandemic, where a basic understanding of disease transmission can drastically improve adherence to public health guidelines and quality distance learning could diminish the impacts of school closings. The research will contribute to the understanding of cellular mechanisms that drive adaptation and survival in response to environmental stress. These responses are critical for early-branching eukaryotic protozoa, such as Apicomplexans, that thrive in a variety of environments during their complex life cycles. Apicomplexan protozoa are expected to harbor the basic components required for a robust stress response due to their early divergence from higher eukaryotes and the physiological buffering provided by their intracellular parasitic lifestyle. Plasmodium, one Apicomplexan genus, retains a heat shock response and translational inhibition, yet nutrient signaling pathways lack key homologues (i.e. the mTOR kinase). This project will bolster the use of computational tools for cross-species comparisons and generate open access multi-omics data sets and mutant parasite lines for use by the research community. Furthermore, identifying aspects of the Apicomplexan stress response that are divergent from higher organisms will challenge prevailing views of the stress response field by highlighting the critical, basic capabilities needed to survive in diverse environments.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.