Research Initiation Award: The Dynamics of Apoptosis in Leishmania donovani and the Genes Involved

研究启动奖为传统黑人学院和大学的初级和中期职业教师提供支持，他们正在建立新的研究项目或重新指导和重建现有的研究项目。期望该奖项有助于提高教师的研究能力和效率，改善所在机构的研究和教学，并使本科生参与研究经验。授予莫尔豪斯学院的奖项有可能在几个领域扩大影响。这个项目的目标是研究一个模式单一生物的程序性细胞死亡。对这种生物中程序细胞死亡的理解可以作为解剖高等生物死亡途径的一个模型。这项工作将使少数族裔学生接触到细胞生物学、寄生虫学、分子生物学和生物信息学。目前，我们缺乏关于单细胞生物中协调程序性细胞死亡（PCD）的专用分子途径的知识。我们感兴趣的是细胞凋亡，这是PCD的一种形式，具有一些保守的特征，如细胞收缩、质膜起泡和DNA断裂。细胞凋亡在单细胞生物中的发生仍然是一个有争议的问题，其解决可能对我们对进化过程的理解具有重要意义。虽然研究提供了包括利什曼原虫在内的单细胞生物中细胞凋亡的证据，但尚不清楚利什曼原虫的细胞凋亡是否与多细胞生物中发现的细胞凋亡标志物相同，如果是的话，驱动这一过程的机制是什么。本研究的目的是研究多诺瓦利什曼原虫的细胞凋亡特征，以促进对多诺瓦利什曼原虫凋亡相关蛋白的鉴定和评价。具体而言，本项目的研究目的是：1)通过检测细胞凋亡的形态学和生化特征来评估细胞凋亡的动力学；2)使用RNA-Seq分析正常细胞群和凋亡细胞群的基因表达。该项目可能为单细胞细胞凋亡提供新的见解，其中潜在的新型转录因子不同于（或可能与）多细胞生物中的凋亡蛋白。对利什曼原虫细胞凋亡的理解也可以作为解剖凋亡途径和分析高等真核生物细胞凋亡的模型。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。

Research Initiation Awards provide support for junior and mid-career faculty at Historically Black Colleges and Universities who are building new research programs or redirecting and rebuilding existing research programs. It is expected that the award helps to further the faculty member's research capability and effectiveness, improve research and teaching at the home institution, and involves undergraduate students in research experiences. The award to Morehouse College has potential to broaden impacts in several areas. The goal of this project is to study programmed cell death in a model single organism. Comprehension of program cell death in this organism may serve as a model to dissect death pathways in higher organisms. The proposed work will expose underrepresented minority students to cell biology, parasitology, molecular biology and bioinformatics.Currently, we lack knowledge regarding the dedicated molecular pathways that coordinate programmed cellular death (PCD) in single-celled organisms. Of interest is apoptosis, a form of PCD characterized by several conserved features such as cell shrinkage, plasma membrane blebbing, and DNA fragmentation. The occurrence of apoptosis in single-celled organisms remains a debated issue, the resolution of which may have significant implications on our understanding of evolutionary processes. While studies have provided evidence of apoptosis in single-celled organisms, including Leishmania, it remains unclear whether apoptosis in Leishmania shares markers of apoptosis with those found in multicellular organisms, and if so, what mechanisms drive the process. The goal of the proposed study is to characterize apoptosis in Leishmania donovani to advance knowledge towards the identification and evaluation of proteins involved in apoptosis in L. donovani. Specifically, the research aims of this project are to: 1) evaluate the kinetics of apoptosis by examining morphological and biochemical features of apoptosis and 2) analyze gene expression in normal and apoptotic cell populations using RNA-Seq analysis. The proposed project may provide new insight into unicellular apoptosis with potentially novel transcriptional players that are distinct from (or perhaps distantly related to) apoptotic proteins in multicellular organisms. The understanding of apoptosis in Leishmania may also serve as a model to dissect apoptotic pathways and analyze apoptosis in higher eukaryotes.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.