Stephen Osmani

Professor & Ohio Eminent Scholar
Faculty

My laboratory is conducting research aimed at elucidating how the cell cycle is regulated with focus on the regulation of mitosis, the universal mechanism by which our DNA is segregated equally to daughter cells during growth and development. We utilize the model filamentous fungus Aspergillus nidulans in these studies. This enables us to use the power of classical genetics (including the parasexual cycle and heterokaryon rescue), molecular genetics, cell biology, genomics/proteomics, and biochemistry to identify and study novel proteins involved in cell cycle regulation. These findings will provide insights into how mitosis is regulated in filamentous fungi, a poorly understood group of organisms which have far-reaching beneficial and detrimental impacts on mankind. The findings should also provide insights into how mitosis is regulated in higher eukaryotes with implications for how cancer develops and can be treated.

Recent work in the lab has focused on understanding how nuclear transport is regulated during mitosis. In higher eukaryotes the nuclear envelope is dismantled during mitosis (open mitosis) by ill-defined mechanisms. However in fungi, such as A. nidulans, mitosis occurs within intact nuclei (closed mitosis). During closed mitosis, proteins such as tubulin which forms the mitotic spindle enter nuclei only during mitosis. It had long been assumed that specific transport pathways through nuclear pore complexes Figure 1(NPCs, the structures providing regulated conduits across the nuclear envelope between the cytoplasm and the nucleoplasm) were modified during closed mitosis. However, our recent findings have demonstrated that in A. nidulans NPCs are opened to allow diffusion in and out of nuclei during mitosis rather than specific transport pathways being modified. This is achieved by the release of over half of the ~30 NPC proteins from NPCs specifically during mitosis (See Figure, taken from Osmani et al., Molecular Biology of the Cell 2006). 

The NPC proteins that remain form a core conduit between the inside and outside of nuclei. During exit from mitosis the dispersed NPC proteins return back to the core NPC structure and reestablish regulated transport. These findings provide a new paradigm for how mitosis can be regulated and indicate A. nidulans mitosis is an intermediate in complexity between closed and open mitoses.

In addition to explaining how nuclear transport is regulated during A. nidulans mitosis these new findings provide a framework to help decipher how the massive NPC structure is first dismantled then reassembled during mitosis. We know that protein phosphorylation plays a critical role and we have shown that the NIMA and Cdk1 mitotic kinases promote disassembly of the NPC. The challenge now is to define which NPC proteins are phosphorylated then dephosphorylated to reversibly disassemble the NPC during mitosis. Also of interest is how proteins released from NPCs during mitosis play roles to facilitate mitotic progression and coordinate nuclear restructuring with successful high fidelity DNA segregation.

 

Osmani lab staff

 

Osmani Lab Members

Graduate Students:

  • Mahesh Chemudupati
  • Nandini Shukla
  • Subbulakshmi Suresh

Research Staff:

  • Aysha Osmani

Undergraduate Students:

  • Nichole Bishop
  • Alisha Lad
  • Andrew Goodall

Current Projects

 Nandini Shukla

Nandini Shukla

Analysis of novel proteins acting at the interface between nuclear pore complex associated proteins and the cytoskeleton.
 Subbulakshmi Suresh

Subbulakshmi Suresh

Analysis of a new nuclear pore complex protein having dual roles, one at interphase nuclear pores and another at mitotic chromatin.
 Mahesh Chemudupati

Mahesh Chemudupati

  1. Understanding the regulation of the dynamic changes in location of proteins between nuclear pores and the inner nuclear membrane during transitions through mitosis.
  2. Development of techniques to enable synthetic lethal screens in A. nidulans.
 Aysha Osmani

Aysha Osmani

  1. Generation of a complete set of protein kinase deletion strains of A. nidulans.
  2. Defining gene functions by systematic deletion, localization and affinity purification coupled with proteomic analyses.
  3. Training people as they join the lab and start to work with A. nidulans.
  

 

 

Recent Publications

Areas of Expertise
  • Cell Biology of Fungi
  • Aspergillus nidulans Biofilms
  • Gaseous Microenvironments

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Phone:
614-247-6791
Fax:
614-247-6845
804 Riffe Building
496 West 12th Avenue
Columbus, OH 43210-1292