Research Expertise and Interest
cellular morphogenesis, plasma membrane dynamics, microtubule cytoskeletons, cytoskeletal proteins, morphological development
David Drubin is the Ernette Comby Chair in Microbiology and a professor of Cell and Development in the Department of Molecular and Cell Biology. His lab's research aims to elucidate the molecular mechanisms that underlie cellular morphogenesis and plasma membrane dynamics in mammalian cells and in budding yeast. They are studying the functions and structure-function relationships of cytoskeletal proteins involved in morphogenesis and in membrane trafficking, and are elucidating the regulatory circuitry that controls the activity of these cytoskeletal proteins. The approaches employed for these studies include genome-wide functional analyses, genetics and molecular genetics, biochemistry, and real-time image analysis of live cells.
Membrane Trafficking Events in Mammalian Cells and Yeast. Since actin is among the most highly conserved proteins known, the results obtained from studies on yeast actin cytoskeleton are expected to be directly transferable to more complex eukaryotes including humans. Defects in trafficking events and cytoskeletal proteins are linked to human diseases such as cancer and neuronal degeneration. While the lab does many studies in budding yeast, more recently the lab began to isolate and characterize mammalian homologues of cytoskeletal proteins that they first identified and characterized in yeast. The Drubin lab is particularly interested in determining the roles of these proteins in endocytosis and Golgi trafficking. One protein, huntingtin-interacting protein 1R (Hip1R), which binds to the Huntingtin disease protein, plays a critical role in productively harnessing forces of actin polymerization for steps in membrane trafficking.
Actin Assembly. Elucidation of the molecular mechanisms used to regulate actin assembly will require a detailed knowledge of how actin subunits assemble into long polymers, and how proteins that bind to monomers and polymers affect assembly dynamics. The lab has performed a structure-function analysis of actin by mutating residues involved in nucleotide hydrolysis and assaying the effects of these mutations on actin assembly in vitro and in vivo. In complementary studies, genetic, biochemical and structural studies of the low molecular weight (16 kD) actin filament severing protein cofilin and its cofactor, Aip1p, and the actin nucleotide exchange factor, profilin, are being performed to determine how filament turnover is controlled in vivo. The lab also identified and are studying several novel activators of the Arp2/3 complex, which regulates actin nucleation, and they are also studying the role of nucleotide in Arp2/3 function. By combining genetics with biochemistry, they are able to achieve a deeper understanding of actin regulation than would have been possible using either approach alone.