UCR

Plant Pathology Graduate Program



Katherine A. Borkovich


Katherine A. Borkovich
Office: 951-827-2753
Fax:
1234B Genomics
Office Hours: , not specified - not specified
Email: katherine.borkovich@ucr.edu

Katherine A. Borkovich

Department Chair

Professor of Plant Pathology & Fungal Cell Biologist/Biochemist

Fungal cell and molecular biology; functional genomics of fungi

Ph.D. Biochemistry 1985 -- University of California, Los Angeles 
B.S. Biochemistry (with Highest Honors) 1979 -- University of California, Davis


Biography & Research Interests

 

Heterotrimeric G Proteins

Heterotrimeric (αβγ) G proteins control major signal transduction pathways in eukaryotes. Their importance is underscored by the fact that more than 30% of pharmaceutical drugs target G protein signaling pathways. My laboratory discovered heterotrimeric G proteins in filamentous fungi, using the model organism Neurospora crassa. My group has now characterized the myriad functions and physical interactions between three Gα, one Gβ and one Gγ proteins in Neurospora (Won et al. 2012, Eukaryot Cell: 11:1239-48). Since our original discovery, Gα proteins have been implicated in pathogenesis in numerous plant and animal fungal pathogens (reviewed in Li et al. 2007, Ann. Rev. Microbiol. 61:423-52). Therefore, our work is relevant to development of new infection control practices and identification of targets for chemical agents to combat fungal diseases in plants and animals.

A recent breakthrough was our identification in Neurospora of a novel activator of Gα proteins, RIC8 (Wright et al. 2011, Genetics189: 1-12). RIC8 is found in animals and certain fungi, but is absent from the genomes of the model fungus Saccharomyces cerevisiae and sequenced plants, making Neurospora an ideal model for study of RIC8 function. RIC8 is essential for polar growth and development in Neurospora. Using genetics, genomics and biochemical approaches, we demonstrated that RIC8 regulates GTP binding and the stability of two Gα proteins, and downstream cAMP signaling. Our results highlight the critical role that RIC8 plays in cell growth and development and underscore important parallels between the functions of RIC8 in Neurospora and animal systems. Our work with G protein signaling has been funded by grants from the National Institutes of Health (NIH).

 

Systems Biology

Neurospora is the NIH model organism for the filamentous fungi, the group of organisms most closely related to animals and which includes important pathogens of animals and plants. I was heavily involved in the effort to sequence and annotate the Neurospora genome (Galagan et al. 2003, Nature 422: 859-868; Borkovich et al. 2004, Microbiol. Mol. Biol. Rev.52: 1-108).  Since 2004, I have been Co-PI of an NIH Program Project (P01) grant for functional genomics of Neurospora. My laboratory has been involved in the genome-wide targeted gene replacement project that has successfully mutated nearly all of the nearly 10,000 genes (Colot et al. 2006, Proc. Natl. Acad. Sci. USA 103:10352-7; Park et al. 2011, Methods Mol. Biol. 722:179-89). We have also completed large-scale analysis of mutants for ~90 Neurospora serine/threonine protein kinase genes, including growth, morphological and chemical sensitivity screens (Park and Servin et al. 2011, Eukaryot Cell. 10:1553-64). Notably, this work uncovered possible functions for 71% of the kinases, including many unstudied and/or hypothetical proteins in fungi and animals, providing new avenues of research for detailed analysis of these kinases.

I have participated in the NSF-funded UCR ChemGen IGERT training grant focused on screens to identify chemicals that affect the biology of plants and plant pathogens. One IGERT fellow in my group has investigated compounds that influence formation and germination of asexual spores, the primary cell type used for dissemination by many pathogenic fungi. Another IGERT fellow has identified a chemical that disrupt interactions between proteins involved in G protein signaling, with the goal of disrupting cell growth. With funding from the IGERT, we collaborated with Kayla Kaiser and Dr. Cynthia Larive in the Chemistry Department to perform the first proton NMR metabonomics profiling of Neurospora (Kim et al. 2011, Eukaryot. Cell. 10:820-31). We demonstrated differences in the global metabonome of asexual spores and carbon-sufficient and carbon-starved cultures. We also determined effects on the metabolome resulting from mutation of a Gα protein gene that controls asexual sporulation.

 

Fusarium oxysporum Pathogenesis

Members of the Fusarium oxysporum species complex are root pathogens of numerous crops of economic importance to the United States. Certain subspecies are also opportunistic human pathogens. My group annotated signaling genes in the genome of F. oxysporum f.sp. lycopersici, a fungal pathogen of tomato and animals (Ma et al. 2010, Nature 464:367-73). Production of small RNAs that target and down-regulate specific genes has been associated with infection by microorganisms in other plants. We have collaborated with Drs. Isgouhi Kaloshian and Dr. Jason Stajich at UCR and Dr. Clifford Han at LANL to use next generation sequencing to identify small RNAs from F. oxsporum and tomato that are associated with the disease state (Park and Borkovich, 2012, Methods Mol. Biol. 883:155-64).  Our results revealed two microRNAs that are differentially regulated in resistant (Motelle) and susceptible (Moneymaker) lines of tomato (Ouyang et al., in press). We identified four mRNA targets of these microRNAs and showed that these targets are required for resistance to F. oxysporum  and encode proteins with nucleotide-binding domains found on other plant resistance (R) proteins. The observation that none of the targets correspond to I-2, the only known R gene for F. oxysporum in tomato, supports roles for additional R genes in the immune response.

Awards

  • Fellow, American Academy of Microbiology, 2017
  • Distinguished Teaching Award, UC Riverside, 2016
  • B.O. Dodge Award, for Exceptional Contributions to the Neurospora Community, 2010
  • Fellow, American Association for the Advancement of Science, 2006
  • Dean’s Award for Teaching Excellence, U.T.-Houston Medical School, 2001
  • Dean's Award for Excellence, U.T.-Houston Graduate School of Biomedical Sciences 1995, 1999, 2000
  • American Cancer Society Junior Faculty Research Award, 1994-1997
  • Post-doctoral National Research Service Award (NIH), 1986-1989

Publications

Recent Publications.  For complete listing, search Borkovich KA on Pubmed. 

  •  Ma, L.-J., van der Does HC, Borkovich, K.A., et al. 2010.  Comparative genomics reveals mobile pathogenicity chromosomes in Fusarium, Nature 464:367-73.

    Collopy P.D., Colot H.V., Park G., Ringelberg C., Crew C.M., Borkovich K.A., Dunlap J.C. 2010.  High-throughput construction of gene deletion cassettes for generation of Neurospora crassa knockout strains.  Methods Mol Biol. 638:33-40.

    Jones C.A., Borkovich K.A.2010.  Analysis of mitogen-activated protein kinase phosphorylation in response to stimulation of histidine kinase signaling pathways in Neurospora. Methods Enzymol. 471:319-34.

    Borkovich, K.A. and Ebbole, D.J., Eds. 2010Cellular and molecular biology of filamentous fungi, ASM Press, Washington, D.C., 848 pp.  Edited book.

    Park, G., Jones, C.A., Borkovich, K.A.2010.  “Signal transduction pathways”, in Cellular and molecular biology of filamentous fungi, Eds. K.A. Borkovich, D.J. Ebbole, ASM Press, Washington, D.C., pp. 50-59.

    Park G, Colot HV, Collopy PD, Krystofova S, Crew C, Ringelberg C, Litvinkova L, Altamirano L, Li L, Curilla S., Wang W., Gorrochotegui-Escalante N., Dunlap J.C., Borkovich K.A. 2011.  High-throughput production of gene replacement mutants in Neurospora crassaMethods Mol. Biol. 722:179-89.

    Kim J.D., Kaiser K., Larive C.K., Borkovich K.A.2011.  Use of 1H NMR to measure intracellular metabolite levels during growth and asexual sporulation in Neurospora crassaEukaryot. Cell. 10:820-31.

    Wright S.J., Inchausti R., Eaton C.J., Krystofova S., Borkovich K.A. 2011.  RIC8 is a guanine-nucleotide exchange factor for Gα subunits that regulates growth and development in Neurospora crassaGenetics189: 1-12.

    Park, G., Servin, J.A., Turner, G.E., Altamirano, L., Colot, H.V., Collopy, P., Litvinkova, L., Li, L., Jones, C.A., Diala, F.-G., Dunlap, J.C. and Borkovich, K.A.2011.  Global analysis of serine-threonine protein kinase genes in Neurospora crassa.  Eukaryot Cell. 10:1553-64.

    Park, G., Borkovich, K.A.2012.  Small RNA isolation and library construction in Neurospora and FusariumMethods Mol. Biol. 883:155-64.

    Kim H., Wright S.J., Park G., Ouyang S., Krystofova S., Borkovich K.A. 2012.  Roles for Receptors, pheromones, G proteins and mating type genes during sexual reproduction in Neurospora crassaGenetics 190:1389-404.

    Servin J., Campbell A., Borkovich K.A.2012. “G protein signaling components in filamentous fungal genomes”. In Biocommunication of fungi. Günther Witzany, editor. Springer Science+Business Media, Dordrecht, Germany.

    Kim J., Schacht P.C., Garud A., Park G., Borkovich K.A.2012. “Heterotrimeric G proteins”. In Neurospora: Genomics and molecular biology. McCluskey K, Kasbekar DP, editors. Horizon Scientific Press.

    Won S., Michkov, A.V., Krystofova, S., Garud, A.V., Borkovich K.A. 2012.  Genetic and physical interactions between Gα subunits and components of the Gβγ dimer of heterotrimeric G proteins in Neurospora crassa. Eukaryot Cell: 11:1239-48.

    Eaton C.J., Cabrera I.E., Servin J.A., Wright S.J., Cox M.P., Borkovich K.A. 2012.  The guanine nucleotide exchange factor RIC8 regulates conidial germination through Gα proteins in Neurospora crassaPLoS One 7(10):e48026.

  • Park, G., Borkovich, K.A. 2012. Small RNA isolation and library construction for expression profiling of small RNAs from Neurospora and Fusarium using Illumina high throughput deep sequencing. Methods Mol. Biol. 883:155-64.

  • Ghosh, A., Servin, J.A., Park, G., Borkovich, K.A. 2014. Global analysis of serine/threonine and tyrosine protein phosphatase catalytic subunit genes in Neurospora crassa reveals interplay between phosphatases and the p38 MAPK. G3: Genes, Genomes, Genetics 4:349-365.

  • Ouyang, S., Park, G., Atamian, H., Han, C., Stajich, J.E., Kaloshian, I., Borkovich, K.A.2014. MicroRNAs suppress NB domain genes in tomato that confer resistance to Fusarium oxysporum. PLoS Pathogens 10:e1004464.
  • Cabrera IE, Tambo AL, Cruz A, Guan BX, Bhanu B, Borkovich KA. 2015. Quantitative analyses using Video Bioinformatics and image analysis tools during growth and development in the filamentous fungus, Neurospora crassa. In Video Bioinformatics. Computational Biology, Image Processing, Computer Vision, and Pattern Recognition. Editors: Bir Bhanu and Prue Talbot. Springer. Vol. 22, p. 237-50.
  • Cabrera, IE, Pacentine IV, Lim A, Guerrero N, Krystofova S, Li L, Michkov AV, Servin JA, Ahrendt SR, Carrillo AJ, Davidson LM, Barsoum AH, Cao J, Castillo R, Chen W, Dinkchian A, Kim S, Kitada SM, Lai TH, Mach A, Malekyan C, Moua TR, Torres CR, Yamamoto A, Borkovich KA.2015. Global analysis of predicted G protein coupled receptor genes in the filamentous fungus, Neurospora crassa. G3: Genes|Genomes|Genetics 5:2729-43.

Ouyang, S., Beecher, C.N., Wang, K., Larive, C.K., Borkovich, K.A. 2015. Metabolic impacts of using nitrogen and copper-regulated promoters to regulate gene expression in Neurospora crassa. G3: Genes/Genomes/Genetics 5:1899-1908.

R Tamuli, R Deka and KA Borkovich. 2016. Calcineurin subunits A and B interact to regulate growth and asexual and sexual development in Neurospora crassa. PLoS ONE 11:e0151867. 


Park, G, Ouyang, S, Borkovich, KA. 2016. High-throughput construction of genetically modified fungi. Gene expression systems of fungi: applications and advancements. Editors: Monika Schmoll, Christoph Dattenböck, Springer Science+Business Media, p.241-52.

AJ Carrillo, P Schacht, IE Cabrera, Johnathon Blahut, Loren Prudhomme, Sarah Dietrich, Thomas Bekman, J Mei, C Carrera, V Chen, I Clark, G Fierro, L Ganzen, J Orellana, S Wise, K Yang, H Zhong and KA Borkovich. Functional profiling of transcription factor genes in Neurospora crassa. G3: Genes|Genomes|Genetics, submitted.

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