Michelle Momany

Research in my lab focuses on polar growth in the model filamentous fungus Aspergillus nidulans and the pathogen Aspergillus fumigatus. One major project in the lab is examining septins, novel cytoskeletal proteins, in A. nidulans. Work in other systems has shown that the septins function as scaffolds, organizing the division plane and other areas of new cell growth. Research in our lab has shown that there are 5 septins in A. nidulans and that one of those septins localizes to septa, forming branches and conidiophore layers. The filamentous localization of A. nidulans septins is especially exciting because it furnishes an experimentally tractable system to investigate the significance of the septin filaments previously only reported in animals.

The other major project in the lab is looking at gene expression and polar growth in A. fumigatus. A. fumigatus causes invasive aspergillosis, an often fatal disease of the immunocompromised. We are using microarrays and deep sequencing to study the genes that are expressed in the early growth of this fungus.

Filamentous fungi are important in a variety of environmental niches as primary degraders of organic carbon, are widely used by industry for the production of enzymes and pharmaceuticals and can be important pathogens of plants and animals. Central to all of these roles is the ability to grow in a highly polar manner, secrete enzymes and invade substrates. Proper growth of the fungal cell requires coordination of nuclear division, cytokinesis, and deposition of new cell wall material. To better understand fungal growth we are pursuing multiple projects in Aspergillus species.

SEPTINS IN ASPERGILLUS NIDULANS

Every cell must have a mechanism for doubling its contents and correctly partitioning those contents to daughter cells. The timing of division must be delayed until genetic and cellular materials have doubled. The plane of division must be specified so that each cell gets everything needed for growth. In multicellular organisms, divisions must be coordinated among different cell types and cellular materials must be transported to the appropriate locations. In highly polar organisms such as filamentous fungi this coordination and transport often takes place over relatively large distances.

The septins function as molecular scaffolds and diffusion barriers, recruiting other proteins to the division site and maintaining the integrity of compartments. They also play roles in membrane recycling and cytoskeletal organization. Septins are central to orderly cell division in fungi and animals. They also appear to be major determinants of morphology and development, likely as a result of their roles in organizing division planes and cytoskeletal elements. While a great deal has been learned about the functions of septins in unicellular yeast, much less is known about their functions in multicellular organisms. We are using the model filamentous fungus A. nidulans to investigate the idea that changes in the organization of septins result in changes in the proteins that are recruited and tethered on septin scaffolds and ultimately in changes in cell morphology.

POLAR GROWTH IN ASPERGILLUS FUMIGATUS

Invasive aspergillosis (IA) is the most frequent infectious cause of death in leukemia and bone marrow transplant patients, and is now seen more often than invasive candidiasis. The conidia of Aspergillus fumigatus, the filamentous fungus that is the most common cause of IA, are ubiquitous in the environment. These small, round spores are frequently inhaled, but a competent immune system clears them before they cause disease. In vitro studies have shown that after breaking dormancy, the reactivated A. fumigatus conidium undergoes a brief period of isotropic expansion before a germ tube emerges. As is true for all filamentous fungi, later growth is highly polar occurring exclusively at the tips of hyphae that develop from germ tubes or at the tips of branches that emerge from primary hyphae. This highly polar tip growth allows A. fumigatus to invade blood vessels and tissues resulting in the necrosis characteristic of IA. We are using microarray profiling, laser microcapture and deep sequencing to profile genes that are differentially transcribed and/or asymmetrically localized during polar growth of germ tubes, hyphae and branches in A. fumigatus.