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

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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.