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应激条件。这些反应可以决定细胞是死亡还是存活，根据新的环境(即不同的温度、营养水平或化学组成)而变化。这个项目将使用单细胞有机体来更多地了解细胞如何应对压力。具体地说，疟原虫细胞生存在广泛的环境中，因为它们生活在宿主细胞内外以及不同的动物体内。这些细胞使用一些与多细胞动物相同的方法，但有显著的差异。由于它们能够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着在不同环境中生存所需的最低限度的成分，并可能为其他单细胞生物体如何适应压力提供洞察。这项工作的更广泛影响包括内在研究，因为这一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。其他活动寻求通过使用虚拟教育工具将研究与教育推广计划相结合来提高公众识字能力，虚拟教育工具以准确和令人兴奋的方式描述及时的生物学主题。在全球大流行期间，这一点尤其重要，在这种情况下，对疾病传播的基本了解可以极大地提高对公共卫生准则的遵守，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在应对环境压力时驱动适应和生存的细胞机制。这些反应对于早期分枝的真核原生动物至关重要，例如Apicomplexans，它们在复杂的生命周期中在各种环境中茁壮成长。Apicomplexan原生动物由于早期与高等真核生物的差异以及其细胞内寄生生活方式提供的生理缓冲，被认为具有强大的应激反应所需的基本成分。疟原虫是Apicomplexan属中的一个属，它保留了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)。该项目将支持使用计算工具进行跨物种比较，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，识别Apicomplexan应激反应的不同于高等生物的方面，将通过强调在不同环境中生存所需的关键、基本能力来挑战应激反应领域的主流观点。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。

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.