N. Louise Glass

Professor
Ph.D.  University of California-Davis, 1986
  

341A Koshland Hall
Berkeley, California 94720
lglass@berkeley.edu
office: 510-643-2399   lab: 510-643-2546   fax:  510-642-4995

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Cell specialization, cell communication and nonself recognition are crucial mechanisms in microbial organisms such as filamentous fungi. In filamentous fungi, growth occurs by hyphal tip extension, branching and repeated fusion of hyphae, ultimately forming an exquisitely connected network, from which the individual colony grows and reproduces. My research interests are focused on understanding communication and signaling mechanisms that mediate the hyphal fusion process and nonself recognition mechanisms that occur before and after hyphal fusion. The experimental tractability and availability of a large number of mutants in the filamentous fungus, Neurospora crassa, makes it a superb system to delineate both fungal-specific and general mechanisms of cell communication and nonself recognition. We use a combination of molecular biology, genetics, cell biology, genomics and bioinformatics to investigate the molecular and cellular basis of nonself recognition during both sexual and asexual phases of growth in filamentous fungi.

Self/nonself discrimination is a ubiquitous and essential function of both multicellular and microbial species, and is an aspect of biology that has long fascinated scientists. Nonself recognition in filamentous fungi is mediated by differences at het (for heterokaryon incompatibility) loci. Hyphal fusion between two individuals that have genetic differences at het loci triggers programmed cell death (PCD)of the fusion cell. Nonself recognition and PCD functions to prevent transfer of mycoviruses and senescence plasmids between fungal individuals within a population. Our current research objectives include elucidating the molecular mechanism of nonself recognition, understanding how nonself recognition triggers fungal PCD and investigations into the evolution of nonself recognition systems in fungi.

The ability to form a hyphal network is a hallmark of filamentous fungi. In filamentous ascomycete species such as Neurospora crassa, an individual hypha (a multinucleate, multicellular filament with incomplete crosswalls, or septa) grows by hyphal tip extension and branching. Behind the growing colony margin, fusions between hyphae are continuously formed (a process called anastomosis), yielding a network of interconnected hyphae, or mycelium, that makes up the fungal individual. Although the capacity to form a hyphal network is ubiquitous in filamentous fungi, little is known about the mechanism or function of an interconnected hyphal network. We have characterized a number of hyphal and germling fusion mutants in N. crassa, including strains with lesions in genes encoding MAP kinase signal transduction components and a number of transcription factors. Our current research objectives include determining the molecular mechanism of self-signling and the nature of the signaling molecules, the relationship of the signal transduction pathway to the fungal cytoskeleton and identifying target genes of transcription factors which are required for the germling and fusion process.

As part of a group dedicated to the functional analysis of the model filamentous fungus, Neurospora crassa, we have oligonucleotide microarrays to the predicted 10,032 genes of Neurospora crassa. We are performing baseline transcriptional profiling of N. crassa during growth and reproduction and are currently focusing on identifying transcriptional regulatory networks by profiling ~ 100 transcription factor knockout mutants generated by the Neurospora Functional Genomics Group (http://www.dartmouth.edu/~neurosporagenome/.

Read, N.D., A. Fleissner, M.G. Roca and N. L. Glass, 2009. Hyphal Fusion. In Cellular and Molecular Biology of Filamentous Fungi, Eds. K. Borkovich, D. Ebbole and M. Momany (in press).

Videira, A,. T. Kasuga, C. Tian, C. Lemos, A. Castro and N. L. Glass, 2009. Transcriptional analysis of the Neurospora crassa response to phytospingosine reveals links to mitochondrial function. Microbiol (in press).

Kasuga, T., G. Mannhaupt and N. L. Glass, 2009. Relationship between phylogenetic distribution and genomic features in Neurospora crassa. PLoS One 4::e5286.

Fleissner, A., S. Diamond and N. L Glass, 2009. The Saccharomyces cerevisiae PRM1 homolog in Neurospora crassa is involved in vegetative and sexual cell fusion events, but also has post-fertilization functions. Genetics 181:497-510 .

Fleissner, A., A. R. Simonin and N. L. Glass, 2008. Cell fusion in the filamentous fungus, Neurospora crassa. Methods Mol Biol. 2008;475:21-38.

Kasuga, T. and N. L Glass, 2008. Dissecting colony development of Neurospora crassa using mRNA profiling and comparative genomics approaches.Eukaryot Cell. 7:1549-1564.

Castro, A., C. Lemos, A. Falcão, N. L. Glass and A. Videira, 2008. Increased resistance to complex I mutants to phytosphingosine-induced programmed cell death. J Biol Chem 283:19314-19321.

Rasmussen, C. G., R. M. Morgenstein, S. Peck and N. L. Glass, 2008. Lack of the GTPase RHO-4 in Neurospora crassa causes a reduction in numbers and aberrant stabilization of microtubules at hyphal tips. Fungal Genet Biol 45:1027-1039.

Wichmann G., J. Sun, K. Dementhon, N.L. Glass and S. E. Lindow, 2008. A novel gene, phcA from Pseudomonas syringae induces programmed cell death in the filamentous fungus Neurospora crassa. Mol Microbiol 68:672-689

Rasmussen, C. G. and N. L. Glass, 2007. Localization of RHO-4 indicates differential regulation of conidial versus vegetative septation in the filamentous fungus Neurospora crassa. Eukaryot Cell 6:1097-107

Dunlap, J.C., K.A. Borkovich, M.R. Henn, G.E. Turner, M.S. Sachs, N.L. Glass, K. McClusky, M. Plamann, J.E. Galagan, B.W. Birren et al., 2007. Enabling a community to dissect an organism—Overview of The Neurospora Functional Genomics Project. Adv Genetics 57:49-96.

Tian, C., T. Kasuga, M. S. Sachs and N. L. Glass, 2007. Transcriptional profiling of cross pathway control in Neurospora crassa: Comparative analysis of the Gcn4 and CPC1 regulons. Eukaryot Cell 6:1018-29.

Fleissner, A. and N. L. Glass, 2007. SO, a protein involved in hyphal fusion in Neurospora crassa, localizes to septal plugs. Eukaryot Cell 6:84-94.

Dementhon, K., G. Iyer and N. L. Glass, 2006. VIB-1 is required for expression of genes necessary for PCD in Neurospora. Eukaryot Cell 5:2161-2173.

Glass, N. L. and K. Dementhon, 2006. Nonself recognition and programmed cell death in filamentous fungi. Curr Opin Microbiol 9:553-558.

Kaneko, I., K. Dementhon, Q. Xiang and N. L. Glass, 2006. Non-allelic interactions between het-c and a polymorphic locus, pin-c, are essential for nonself recognition and programmed cell death in Neurospora crassa. Genetics 172:1545-55.

Kasuga, T., J.P. Townsend, C. Tian, L.B. Gilbert, G. Mannhaupt, J.W. Taylor and N.L. Glass, 2005. Long-oligomer microarray profiling in Neurospora crassa reveals the transcriptional program underlying biochemical and physiological events of conidial germination. Nucleic Acids Res. 33:6469-85.

Rasmussen, C. G. and N. L. Glass, 2005. A rho-type GTPase, rho-4, is required for septation in Neurospora crassa. Eukaryot Cell. 4:1913-1925.

Fleißner, A., S. Sarkar, D. J. Jacobson, M. G. Roca, N. D. Read and N. L. Glass, 2005. Identification and characterization of so, a hyphal fusion mutant of Neurospora crassa. Eukaryot Cell 4:920-30.

Xiang, Q. and N. L. Glass, 2004. The control of mating type heterokaryon incompatibility by vib-1, a locus involved in het-c incompatibility in Neurospora crassa. Fungal Genet Biol 41:1063-1076.

Pandey, A. M. G. Roca, N. D. Read and N. L. Glass, 2004. Role of a mitogen-activated kinase in hyphal fusion and conidial germination in Neurospora crassa. Eukaryot Cell 3:348-58.

Glass, N.L., C. Rasmussen, M.G. Roca and N.D. Read. 2004 Hyphal homing, fusion and mycelial interconnectedness. Trends Microbiol 12:135-41.

Jacobson, D. J., A. J. Powell, J. R. Dettman, G. S. Saenz, M. M. Barton, M. D. Hiltz, W. H. Dvorachek, Jr., N. L. Glass, J. W. Taylor and D. O. Natvig, 2004. Neurospora in temperate forests of western North America. Mycologia 96:66-74.

Xiang, Q. and N. L. Glass, 2004. Chromosome rearrangements in isolates that escape from het-c heterokaryon incompatibility in Neurospora crassa Curr Genet 44:329-38.

Glass, N.L. and I. Kaneko 2003. Fatal attraction: Nonself recognition and heterokaryon incompatibility in filamentous fungi. Euk Cell 2:1-8.

Marek, S. M., J. Wu, N. L. Glass, D. G. Gilchrist and R. M. Bostock, 2003. Nuclear DNA degradation during heterokaryon incompatibility in Neurospora crassa Fungal Genet Biol 40: 126-137.

Kroken, S., N. L. Glass, J. W. Taylor, O.C. Yoder and B. G. Turgeon, 2003. Phylogenomics of type I polyketide synthases in plant pathogenic and saprobic ascomcyete fungi Proc Natl Acad Sci USA 100:15670-5.

Galagan, J. et al., 2003. The genome sequence of the filamentous fungus Neurospora crassa Nature 422: 859-868.

Sarkar, S., G. Iyer, J. Wu and N. L. Glass, 2002. Nonself recognition is mediated by HET-C heterocomplex formation during vegetative incompatibility. EMBO J 18: 4841-4850.

Xiang, Q. and N. L. Glass, 2002. Identification of vib-1, a locus involved in vegetative incompatibility mediated by het-c in Neurospora crassa. Genetics 162:89-101.

Hickey, P.C., D. J. Jacobson, N. D. Read and N. L. Glass, 2002. Live-cell imaging of vegetative hyphal fusion in Neurospora crassa. Fungal Genet Biol 37: 109-119.

Muirhead, C. A., N. L. Glass and M. Slatkin, 2002. Multi-locus self-recognition systems in fungi as a cause of trans-species polymorphism. Genetics 161:633-641.

Xiang, Q., Rasmussen, C. and N. L. Glass, 2002. The ham-2 locus, encoding a putative transmembrane protein, is involved in hyphal fusion in Neurospora crassa Genetics 160:169-180.

Wu, J, and N. L. Glass, 2001. Identification of specificity determinants and the generation of alleles with novel specificity at the het-c heterokaryon incompatibility locus of Neurospora crassa. Mol Cell Biol 21:1045-1057.