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

研究启动奖为历史悠久的黑人学院和大学的初级和职业生涯中期教师提供支持，这些教师正在建立新的研究计划或重新定向和重建现有的研究计划。预计该奖项有助于进一步提高教师的研究能力和有效性，改善所在机构的研究和教学，并让本科生参与研究经验。授予莫尔豪斯学院的奖项有可能扩大几个领域的影响。这个项目的目标是研究单个生物体模型中的程序性细胞死亡。对这种生物体中程序性细胞死亡的理解可以作为剖析高等生物体中死亡途径的模型。这项拟议的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，我们缺乏关于协调单细胞生物体中程序性细胞死亡(PCD)的专门分子途径的知识。令人感兴趣的是细胞凋亡，这是一种PCD，其特征是几个保守的特征，如细胞收缩、质膜起泡和DNA片段化。单细胞生物体中细胞凋亡的发生仍然是一个有争议的问题，这个问题的解决可能会对我们理解进化过程产生重大影响。虽然研究已经提供了包括利什曼原虫在内的单细胞生物中存在凋亡的证据，但尚不清楚利什曼原虫中的凋亡是否与多细胞生物体中发现的那些凋亡标志相同，如果是，驱动这一过程的机制是什么。本研究的目的是研究杜氏利什曼原虫的细胞凋亡特征，以促进对杜氏利什曼原虫中与细胞凋亡相关的蛋白质的鉴定和评价。具体地说，本项目的研究目的是：1)通过检测细胞凋亡的形态和生化特征来评估细胞凋亡的动力学；2)利用RNA-Seq分析来分析正常细胞和凋亡细胞群体中的基因表达。这项拟议的项目可能为了解单细胞凋亡提供新的见解，潜在的新的转录因子与多细胞生物体中的凋亡蛋白截然不同(或可能与之有遥远的联系)。利什曼病中对细胞凋亡的理解也可以作为剖析细胞凋亡途径和分析高等真核生物中细胞凋亡的模型。这一奖项反映了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。

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.