Martin Hetzer
Assistant Professor of Biology, Salk Institute

e-mail: hetzer@salk.edu
  

Biogenesis of the cell nucleus

During eukaryotic cell division the complex architecture of the cell nucleus breaks down to allow chromosomes to be captured by the mitotic spindle, which then accurately partitions them to daughter cells. Once segregation is accomplished, the interphase architecture is re-established by unknown mechanisms to enable perpetuation of genomic information.

The most dramatic events during nuclear assembly is the reformation of the nuclear envelope, a highly structured barrier that separates the nuclear interior from the rest of the cell. It is composed of a concentric double membrane that is penetrated by nuclear pores, which serve as channels for transport between the nucleus and the cytoplasm.

The Hetzer Laboratory is focusing on understanding the molecular basis of nuclear assembly and its regulation during cell division. Recently, two lab members, Maximiliano DAngelo and Daniel Anderson, could show that nuclear pore complexes form de novo from both sides of the nuclear membrane (link to press release). Currently Hetzers lab uses live cell imaging and biochemistry as well as genetic and computational approaches to study various aspects of nuclear formation.

Dynamic changes of the nuclear envelope during cell differentiation

The nuclear envelope undergoes dramatic structural changes during cell differentiation. Mutations in nuclear envelope proteins cause a variety of different human diseases, highlighting the importance of the nuclear envelope for cell function. Mammalian nuclei are complex organelles, whose functions depend largely on a spatial, higher order organization of chromatin. Anchorage of chromatin at the nuclear periphery and its three-dimensional organization within the nuclear interior may regulate cell type- and differentiation-specific gene expression.

We are studying the dynamic reorganization of the nuclear envelope during muscle- and neuronal differentiation. Additionally, we are using Drosophila and C. elegans as model systems to identify functional interactions between the nuclear periphery and chromatin.

    Walther, TC, Askjaer, P, Gentzel, M, Habermann, A, Griffiths, G, Wilm, M, Mattaj IW, Hetzer, MW (2003). RanGTP mediates nuclear pore complex assembly. Nature 424: 689-694.

    Hetzer, MW, Walther TC, Mattaj IW. (2005). Pushing the envelope: structure, function, and dynamics of the nuclear periphery. Annu Rev Cell Dev Biol. 21: 347-80.

    D'Angelo, MA, Hetzer MW. (2006). The role of the nuclear envelope in cellular organization. Cell Mol Life Sci. 63: 316-32.

    D'Angelo, MA, Anderson, DJ, Richard, E, Hetzer, MW (2006). Nuclear pores form de novo from both sides of the nuclear envelope. Science 312: 440-443.

    Anderson, DJ, Richard, E, Hetzer, MW (2007) Nuclear envelope formation by chromatin-mediated       reorganization of the endoplamsic reticulum. Nature Cell Biol. in press.

Martin Hetzer received his PhD. from the Vienna Biocenter in Austria. His postdoctoral studies took him to the European Molecular Biology Laboratory in Heidelberg, Germany. He was awarded a EMBO fellowship and was named as an APART Fellow. He was selected as a Pew Scholar in 2005.