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Rebecca W. Heald

Professor of Cell & Developmental Biology

E-mail: heald@socrates.berkeley.edu
Phone: (510) 643-5493
Lab Homepage: http://mcb.berkeley.edu/labs/heald/

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Rebecca W. Heald

Research Interests

The research goal of our laboratory is to understand intracellular morphogenesis at a molecular level; in particular the complex events that underlie cell division.  Our major focus is the mitotic spindle, the dynamic macromolecular machine essential for the correct distribution of chromosomes to each daughter cell. The spindle is composed of microtubule polymers and many other factors that generate an antiparallel bipolar array.  Duplicated sister chromosomes attached to microtubules by their kinetochores are segregated to opposite spindle poles during anaphase.  The spindle also dictates the position of the cleavage plane, where an actin/myosin-based contraction pinches the two daughter cells apart during cytokinesis.  The long term goal of the laboratory is to elucidate the principles that underlie spindle assembly and function, and to identify the roles of individual proteins involved.  We apply diverse and interdisciplinary techniques, including an in vitro celluar extract system, as well as chemical, proteomic and biophysical approaches.

Current Projects

Developing simplified assays to study spindle assembly. Utilizing extracts prepared from eggs of the African frog Xenopus laevis and “artificial chromosomes” consisting of plasmid DNA-coated magnetic beads, we can generate bipolar spindles in vitro in the absence of focal microtubule nucleation centers (centrosomes) or specialized microtubule-chromosome attachment sites (kinetochores). DNA on the beads assembles into chromatin that is sufficient to induce microtubule polymerization and organization, but the molecular mechanisms behind this process are unclear. We are evaluating the roles of candidate chromatin factors and downstream microtubule effectors, including microtubule-associated proteins and motors in spindle assembly, and developing pure component assays directed towards molecular reconstitution.


Spindle assembled around plasmid DNA-coated beads in a cytoplasmic extract.

Elucidating the role of Ran. In collaboration with the laboratory of Karsten Weis, we are studying one pathway important for spindle assembly that depends on the small GTPase Ran. Analogous to its role in interphase nucleocytoplasmic transport, RanGTP generated by the chromatin-bound guanine nucleotide exchange factor RCC1 in mitosis functions to locally discharge cargoes from transport factors in the vicinity of chromosomes that promote spindle assembly. We have used fluorescence energy transfer (FRET) probes to demonstrate a physical gradient of RanGTP and a released cargo surrounding mitotic chromosomes, and are identifying and functionally characterizing the many downstream effectors of this pathway.

Chromosome architecture and cell division. Chromosomes play a critical role in their own transmission, yet the mechanisms determining their higher order organization and mitotic functions are not understood. We are evaluating the roles of several factors including condensin, cohesin, and histone H1 in chromosome condensation and segregation, using microscopy and biophysical approaches.

Using chemical and proteomic approaches to identify cell division factors and elucidate pathways.
We have combined phenotypic screening of chemical libraries with affinity chromatography in Xenopus egg extracts to identify compounds that disrupt spindle assembly and their molecular targets. In a more directed approach, we are screening for inhibitors of the Ran pathway using a FRET assay. Taking advantage of the latest advances in proteomic techniques, we are isolating subcellular structures from dividing mammalian cells, including the cell division remnant (midbody) and mitotic chromosomes to identify constituent proteins, whose function is then evaluated by RNA interference (RNAi) techniques.

Selected Publications

Histone H1 is essential for mitotic chromosome architecture and segregation in Xenopus egg extracts. [T.J. Maresca, B.S Freedman, and R. Heald (2005) J. Cell Biol. 169, 859-869]

A Rae1-containing ribonucleoprotein complex is required for mitotic spindle assembly. [M.D, Blower, M. Nachury, R. Heald,  and K. Weis (2005) Cell 121, 223-234] 

Dissection of the mammalian midbody proteome reveals conserved cytokinesis mechanisms. [A.R. Skop, H. Liu, J.R. Yates 3rd, B.J. Meyer,and R. Heald (2004) Science 305, 61-66]

Centromere glue provides spindle cue.  [R. Deehan and R. Heald (2004) Cell 118, 529-530]

Adenomatous Polyposis Coli associates with the microtubule-destabilizing protein XMCAK. [J.D. Banks and R. Heald (2004) Curr. Biol. 14, 2033-2038]

Identification of a novel protein regulating microtubule stabilitythrough a chemical approach.  [S.M. Wignall, N.S. Gray, Y.-T. Chang, L.Juarez, R. Jacob, A. Burlingame, P.G. Schultz and R. Heald (2004) Chemistry & Biology 11, 135-146]

Burning the spindle at both ends.  [R. Heald (2004) Nature 427, 300-301]

Mechanisms and molecules of the mitotic spindle. [S. Gadde and R. Heald (2004) Curr. Biol. 14, R797-R805] 

The condensin complex is required for proper spindle assembly andchromosome segregation in Xenopus egg extracts.  [S.M. Wignall, R.Deehan, T.J. Maresca and R. Heald (2003) J. Cell Biol. 161, 1041-1051]

Visualization of a RanGTP gradient in interphase and mitotic Xenopus egg extracts. [P. Kalab, K. Weis and R. Heald (2002) Science 295, 2452-2456]

Regulation of Op18 during spindle assembly in Xenopus egg extracts. [P.P. Budde, A. Kumagai, W.G. Dunphy and R. Heald (2001) J. Cell Biol. 153, 149-157]

Last Updated 2005-08-16