Discovery of Fungal Cell Wall Components Using Evolutionary and Functional Genomics

Understanding the various processes/pathways necessary for the biogenesis and maintenance of the cell wall is of immense value as that knowledge can be used for developing antifungals. This dissertation attempts to make a significant contribution in furthering our understanding of the fungal cell wall and its various components. I have identified and characterized genes involved in cell wall growth and maintenance in the model fungus Neurospora crassa by employing a functional screen. I utilized comparative genomics approaches to reconstruct the evolutionary history of cell wall polysaccharides chitin and glucan in the early diverging fungal clades- Microsporidia, Cryptomycota, Chytridiomycota, Blastocladiomycota and Mucormycota. Using a combination of biochemical and comparative genomics I attempted to compare and contrast the cell wall composition of the early diverging fungal clades Chytridiomycota, Blastocladiomycota and Mucormycota to the recently diverged Dikarya fungi. The research presented in this dissertation should lead to the characterization of novel cell wall genes in the filamentous fungi that eventually will lead to development of better drug targets for designing anti-fungal drugs. Also it will lead to better understanding of the cell walls of evolutionarily distinct fungi, which will enable us to combat the pathogenic fungi in a more powerful way. In terms of broader impact this research will be an important contribution to the knowledge of cell wall in the fungal community