Catherine Bachewich, PhD
Affiliate Associate Professor, Biology
The aim of my research is to understand how the cell cycle is regulated and coordinated with differentiation. In one program, we investigate cell cycle control and development in Candida albicans, one of the most common fungal pathogens of humans. C. albicans differentiates into several cell types, including yeast, pseudohyphae or hyphae. This trait is crucial for virulence; cells locked in one form are significantly less pathogenic. Cell cycle signals have profound effects on differentiation and polar morphogenesis in C. albicans, but the basic cell cycle circuitry and mechanisms linking it with development are not well defined. We specifically investigate regulatory aspects of the G1/S transition, mitosis and polar morphogenesis. Our work revealed distinct features that have important implications for new drug target discovery and controlling growth of the pathogen. In a second program, we focus on the roles of a polo-like kinase, PLKA, in cell cycle regulation and development of the filamentous fungus Aspergillus nidulans. Polo-like kinases are multi-functional cell cycle regulators in yeast to humans, up-regulated in many cancers, and play additional roles in metazoan development. We identified PLKA in A. nidulans, which is the only filamentous fungal polo-like kinase characterized to date, and demonstrated that it has many novel functions, including negatively regulating sexual development. Phylogenetic analyses suggest that filamentous fungal polo-like kinases are a distinct group, which has important implications for the evolution of the polo-like kinase family.
Glory, A.,Oostende, C., Geitmann, A and Bachewich,C. (2017). Depletion of the mitotic kinase Cdc5p in Candida albicans results in the formation of elongated buds that switchto the hyphal fate over time in a Ume6p and Hgc1p-dependentmanner. Fungal Genet Biol. 2017 Aug 10;107:51-66. doi: 10.1016/j.fgb.2017.08.002
Mogilevsky, K.*, Glory, A.* and Bachewich, C. 2012. The polo-like kinase PLKA in Aspergillus nidulans is not essential, but plays important roles in vegetative growth and negatively regulates sexual development. Eukaryotic Cell 11, 194-205.
Chou, H., Glory, A. and Bachewich, C. (2011). Orthologues of the APC/C coactivators Cdc20p and Cdh1p are important for mitotic progression and morphogenesis in Candida albicans. Eukaryotic Cell 10, 696-709.
Hussein, B., Huang, H., Glory, A., Osmani, A., Kaminskyj, S., Nantel, A. and Bachewich, C. (2011). G1/S transcription factor orthologues Swi4p and Swi6p are important but not essential for cell proliferation and influence hyphal development in the fungal pathogen Candida albicans. Eukaryotic Cell 10, 384-397.
Whiteway M, Bachewich C. 2007. Morphogenesis in Candida albicans. Annu Rev Microbiol. 61: 529-553.
Whiteway, M. and Bachewich, C. 2006. Signal transduction in the interactions of fungal pathogens and mammalian hosts, in Molecular Principles of Fungal Pathogens, J. Heitman, S.Fuller, J. Edwards and A. Mitchell, Ed. ASM Press, 143-162.
Braun BR, van Het Hoog M, d'Enfert C, Martchenko M, Dungan J, Kuo A, Inglis, DO, Uhl MA, Hogues H, Berriman M, Lorenz M, Levitin A, Oberholzer U, Bachewich,C, Harcus D, Marcil A, Dignard D, Iouk T, Zito R, Frangeul L, Tekaia F, Rutherford K, Wang E, Munro CA, Bates S, Gow NA, Hoyer LL, Kohler G, Morschhauser J, Newport G, Znaidi S, Raymond M, Turcotte B, Sherlock G, Costanzo, M, Ihmels J, Berman J, Sanglard D, Agabian N, Mitchell AP, Johnson AD, Whiteway,M, Nantel A. 2005. A human-curated annotation of the Candida albicans genome. PLoS Genet.1:36-57.
Bachewich C, Nantel A, Whiteway M. 2005. Cell cycle arrest during S or M phase generates polarized growth via distinct signals in Candida albicans. Molecular Microbiolology 57:942-59
Bachewich C, Masker K, Osmani S. 2005. The polo-like kinase PLKA is required for initiation and progression throughmitosis in the filamentous fungus Aspergillus nidulans. Molecular Microbiology 55:572-87.
Bachewich, C. and Whiteway, M. 2005. Cyclin Cln3p links G1 progression to hyphal and pseudohyphal development in C. albicans. Eukaryotic Cell 4:95-102
Bachewich, C. Masker, K. and Osmani, S. 2005. The polo-like kinase PLKA is required for mitotic initiation and progression in the filamentous fungus Aspergillus nidulans. Molecular Microbiology 55: 572-587.
Davies, J., Osmani, A., De Souza C.P.C., Bachewich, C. and Osmani, S. 2005. A potential link between the NIMA mitotic kinase and nuclear membrane fission during mitotic exit in Aspergillus nidulans. Eukaryotic Cell 3: 1433-1444.
Bachewich, C., Thomas, D. and Whiteway, M. 2003. Depletion of a polo-like kinase in Candida albicans activates cyclase-dependent hyphal-like growth. Molecular Biology of the Cell 14, 2163-2180.