DR. PAUL E. MAINS

B.S. (California, Riverside), Ph.D. (Washington) - Professor, Department of Biochemistry & Molecular Biology.

Affiliations:  Member - Genes and Development Research Group.

Research Interests:

Our work focuses on two genetic networks that enable ubiquitous cellular structures, the actin and microtubule-based cytoskeletons, to carry out specific processes critical to C. elegans embryonic development.  The first genetic network that we study focuses on morphogenesis - how a ball of cells (the embryo) is transformed into a tube-shaped worm. This occurs when the epidermal cells on the surface of the embryo contract, squeezing the embryo into its new shape. We found the gene let-502 (which encodes a Rho-binding kinase) and me1-11 (a myosin phosphatase) function with ten other genes to cause the actin cytoskeleton in the embryo's epidermal cells to contract. Homologous contractile pathways mediate rearrangements of the actin-myosin cytoskeleton during the cellular remodelling common to animal embryogenesis, neuronal out growth and smooth muscle contraction.

The second genetic network enables the embryo to change from one mode of cell division to another, from meiosis to mitosis. The microtubule-based spindles for meiosis and mitosis are very different, but occur in the same cytoplasm within a short time of one another. This requires that the products unique to one division be carefully regulated so as not to interfere with the other division. We found that the genes mei-1 and mei-2, which encode subunits of the microtubule-severing protein “katanin”, function to keep meiotic spindle microtubules short in a cytoplasm that will soon support the unusually long microtubules characteristic of the early cleavage spindles.  mei-1/mei-2 activity must be precisely confined to meiosis, otherwise lethal mitotic defects result. This is accomplished through the activity of the gene mel-26, which encodes the substrate-specific adaptor that marks mei-1 protein for ubiquitin-mediated degradation. We are currently studying a system that acts in parallel with mel-26 to degrade mei-1 protein after the completion of meiosis.   In both projects, classical genetic methods are used to identify interacting genes and then molecular approaches are employed to clone the genes and analyze the genetic interactions at the biochemical level.

Developing C. elegans embryos

Personnel:

View Pub Med for Recent publications & abstracts

Recent Publications:

• Johnson, J.L., Lu, C., Raharjo, E., McNally, K., McNally, F.J. and Mains, P.E. (2009) Levels of the ubiquitin ligase substrate adaptor MEL-26 are inversely correlated with MEI-1/katanin microtubule-severing activity during both meiosis and mitosis. Dev. Biol. 330: 349-357.
•  Han, X., Gomes, J.E., Birmingham, C.L., Pintard, L., Sugimoto, A. and Mains, P.E. (2009) The role of protein phosphatase 4 in regulating microtubule severing in the Caenorhabditis elegans embryo. Genetics 181: 933-943.
• Luo, J., Shah, S., Riabowol, K. and Mains, P.E. (2009) The Caenorhabditis elegans ing-3 Gene Regulates Ionizing Radiation-Induced Germ-Cell Apoptosis in a p53-Associated Pathway. Genetics 181: 473-482.
• Lu, C., and Mains, P. E. (2007). The C. elegans anaphase promoting complex and MBK-2/DYRK kinase act redundantly with CUL-3/MEL-26 ubiquitin ligase to degrade MEI-1 microtubule-severing activity after meiosis. Dev. Biol. 302: 438-447.

Contact Information:

The University of Calgary
Room 2211 Health Sciences Centre
3330 Hospital Drive NW, Calgary, Alberta
Canada T2N 4N1
Phone (403) 220-7997
Fax: (403) 270-0737
E-mail: mains [at] ucalgary [dot] ca