BRC-BIO: Polyamine regulated morphogenesis in Candida albicans

Texas A&M International University, Laredo TX

Investigators

Abstract

In certain fungi a family of small positively charged molecules called polyamines modulate a transition from oval yeast-like shapes to filamentous elongated cell types. This shape change has been implicated in the pathogenicity of yeasts such as Candida albicans, the focus of this project. Despite the important role they play in this process, the molecular mechanisms by which polyamines regulate fungal growth and morphogenesis remain enigmatic. This project will use a broad range of research tools to investigate how polyamines in yeasts regulate their own production and affect cell morphogenesis. The knowledge gained will be both of fundamental value and helpful in the identification of drug targets to control human and plant disease-causing fungal growth. Under the direct supervision of the Principal Investigator, the majority of the work will be conducted by undergraduate and graduate students from underrepresented backgrounds at a predominantly Hispanic Serving Institution. The participating students will receive invaluable collaborative and multi-disciplinary training in molecular microbiology, genetics, biochemistry, and bioinformatics. They will thereby become competitive for entry into the biomedical field, broadening the inclusivity and diversity in the STEM workforce. This project reinforces the NSF mission to enhance research productivity in teaching-intensive institutions and broaden the participation of underrepresented groups in biological science. In dimorphic fungi the cellular production of polyamines significantly affects their morphological transition from yeast to filamentous cell types, but the molecular mechanisms mediating this transition are largely unknown. This project will investigate the molecular relationship of intracellular polyamine pools and fungal dimorphism using C. albicans as the model organism. The preliminary observations confirmed the necessity of ornithine decarboxylase and S-adenosylmethionine decarboxylase enzyme activities for yeast morphogenesis; these enzymes are encoded by the SPE1 and SPE2 genes, respectively. A reverse genetics approach will be used to further explore polyamine biosynthesis and regulation in this yeast. Using a variety of morphogenetic assays, metabolic profiling, gene expression analysis, protein expression assays, RNA-Seq based transcriptional profiling, and computer-aided gene annotations, this study will characterize the SPE1 and SPE2 coregulatory function in C. albicans morphogenesis and de novo polyamine biosynthesis. Furthermore, this study will uncover the polyamine-induced filamentation signaling pathways that could be harnessed to identify targets of control to combat the infections caused by this opportunistic plant and human fungal pathogen. Overall, this study will contribute to bridge the knowledge gap between polyamine metabolism and fungal physiology. 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.