University of Pittsburgh Department of Cell Biology
  • Research

    Our laboratory is interested in the fundamental question of how the cell controls the morphology and structure of its membranes.

    We are particularly interested in understanding the mechanism of membrane remodeling by a family of proteins called the dynamin-related proteins (DRPs). This protein family is of enormous interest because its members are intimately involved in membrane remodeling, fusion and division events at many different membranes within the cell. For example, dynamin, the most intensely studied DRP, is responsible for the scission step in endocytosis, a process whereby the cell can internalize small vesicles from the plasma membrane. Other members of the family are required for division and fusion of mitochondria and remodeling of other organelles, such as the endosome.

    We are particularly interested in the function of the DRPs in autophagy-related processes. Autophagy is a collective term that refers to several cellular vacuole or lysosome-targeted degradation pathways. Pathways of autophagy allow a cell to deliver cytosolic components or organelles to the vacuole or lysosome for degradation. Under conditions of cellular stress, autophagy is greatly induced to facilitate adaptation and survival. In humans, impaired autophagy has been linked to a variety of metabolic and age-related disorders, as well as neurodegenerative diseases. For all pathways of autophagy to function properly, extensive remodeling of the membranes of participating organelles is required. Autophagic processes therefore present an outstanding model system to study membrane remodeling.

    Our laboratory is focused on understanding the roles and mechanisms of action of the DRPs in autophagic membrane remodeling events. We use cell biological, structural and high throughput genetic approaches to study pathways of autophagy in our chosen model organism, budding yeast.

  • Publications

    1. Ford MG, Jenni S, Nunnari J. The crystal structure of dynamin. Nature. 2011 Sep 18;477(7366):561-6. doi: 10.1038/nature10441. [link]
    2. Olesen LE, Ford MG, Schmid EM, Vallis Y, Babu MM, Li PH, Mills IG, McMahon HT, Praefcke GJ. Solitary and repetitive binding motifs for the AP2 complex alpha-appendage in amphiphysin and other accessory proteins. J Biol Chem. 2008 Feb 22;283(8):5099-109. Epub 2007 Nov 6. [link]
    3. Schmid EM, Ford MG, Burtey A, Praefcke GJ, Peak-Chew SY, Mills IG, Benmerah A, McMahon HT. Role of the AP2 beta-appendage hub in recruiting partners for clathrin-coated vesicle assembly. PLoS Biol. 2006 Sep;4(9):e262. [link]
    4. Praefcke GJ, Ford MG, Schmid EM, Olesen LE, Gallop JL, Peak-Chew SY, Vallis Y, Babu MM, Mills IG, McMahon HT. Evolving nature of the AP2 alpha-appendage hub during clathrin-coated vesicle endocytosis. EMBO J. 2004 Nov 10;23(22):4371-83. Epub 2004 Oct 21. [link]
    5. Ford MG, Mills IG, Peter BJ, Vallis Y, Praefcke GJ, Evans PR, McMahon HT. Curvature of clathrin-coated pits driven by epsin. Nature. 2002 Sep 26;419(6905):361-6. [link]
    6. Ford MG, Pearse BM, Higgins MK, Vallis Y, Owen DJ, Gibson A, Hopkins CR, Evans PR, McMahon HT. Simultaneous binding of PtdIns(4,5)P2 and clathrin by AP180 in the nucleation of clathrin lattices on membranes. Science. 2001 Feb 9;291(5506):1051-5. [link]


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