Department of Biology

Program

Molecular, Cellular & Developmental Biology

Research Areas

• Developmental Mechanisms and Regulation in Eukaryotic Systems
• Eukaryotic Cell Biology, Cytoskeleton and Signaling
• Evolution

Education

Ph.D., Duke University, 1968

Research Description

The basic question my research addresses is how supra-molecular structures are  constructed:  How does programmed expression of information encoded in linear form in  the genome result in achievement of functional three dimensional cellular morphology?  We study this question at two very different levels: in cells, and in evolution.

In cells:  Control of microtubule function in vivo; the role of  tubulin structure in specification of microtubule architecture;  genetic and proteomic analysis of the motile sperm tail axoneme

We use Drosophila melanogaster as a model system to study assembly and function of  microtubules.  Microtubules are ubiquitous eukaryotic organelles, used to construct many  different arrays that function in many key cellular processes including cell division,  generation and maintenance of cell shape, transport of intracellular components, and the  motility and signaling of cilia and flagella.  Microtubules are assembled from a, b-tubulin  heterodimers.  Each microtubule-based structure has a unique supramolecular architecture,  mode of function, and total spectrum of constituent proteins.  Assembly of each  microtubule-based structure depends on interactions between tubulin heterodimers and  between tubulins and other proteins.  Multicellular organisms express multiple tubulin  isoforms, distinct but related proteins encoded in multi-gene families.  The broad aim of  our research is to determine how these various factors combine to control microtubule  assembly and function in vivo.  We have developed Drosophila spermatogenesis as a  powerful model for structure/function analysis of the metazoan sperm tail axoneme.  We  have shown that all b-tubulins used in motile 9+2 axonemes have a conserved C-terminal  axoneme motif sequence, and that the sequence of the a- and b-tubulins in axoneme  microtubules determines many aspects of axoneme architecture, from microtubule  protofilament substructure, to organization of non-tubulin axoneme proteins.  Current  research combines proteomic and genetic analysis to identify and characterize proteins that  interact with the axoneme tubulins to generate the complex axonemal architecture. 

In evolution:  Evolution of developmental mechanisms and the  determination of body form

The fundamental problem for the study of the evolution of development (evo-devo) is to  determine how developmental processes are modified in evolution to produce novel  features.  We are addressing these questions in a collaborative project with Rudy Raff.  The experimental system uses two closely related Australian sea urchin species with very  different developmental pathways. Heliocidaris tuberculata develops via a long-lived  feeding pluteus larva typical for many sea urchins (indirect developing planktotrophs),  whereas H. erythrogramma develops rapidly via a non-feeding larva (direct developing  lecithotrophs).  The pluteus form is primitive, and H. erythrogramma’s distinctive  developmental mode arose in 4 million years since divergence from H. tuberculata.  We  made the key discovery that H. erythrogramma eggs fertilized with H. tuberculata sperm  generate hybrids that exhibit a novel but harmonius and viable ontogeny.  Both recent and  ancestral echinoderm features are restored in the hybrid developmental program, giving us  direct experimental access to the genic mechanisms that produce new body forms in  evolution.  We have also developed H. erythrogramma as a model system for understanding  preservational modes and biases in Precambrian and Cambrian fossil embryos.

Select Publications

Neil J. Gostling, N. J., C. T. Thomas, J. M. Greenwood, X. Dong, S. Bengtson, E. C. Raff, R. A. Raff, B. M. Degnan, M. Stampanoni and P. C. J. Donoghue.  2008. Experimental taphonomy of lophotrochozoan and deuterostome embryos.  Evolution & Development 10: 339-349.

Raff E. C., Schollaert, K. L., Nelson, D. E.,  Donoghue, P. C. J. , Thomas, C.-W., Turner, F. R., Stein, B. D., Dong, X.,  Bengtson, S., Huldtgren, T., Stampanoni, M., Chongyu, Y., and Raff, R. A.  2008. Embryo fossilization is a biological process mediated by microbial biofilms. Proc Natl. Acad. Sci., 105: 19359-19364.

Popodi, E. M., H. D. Hoyle, F.R. Turner, K. Xu, S. Kruse, and E.C. Raff.  2008.  Axoneme-specific specialization embedded in a ‘generalist’ beta-tubulin.  Cell Motil. Cytoskel. 65: 216–237.

Popodi, E. M., H. D. Hoyle, F.R. Turner, and E.C. Raff.  2008.  Cooperativity beween the beta-tubulin carboxy tail and the body of the molecule is required for axonemes.  Cell Motil. Cytoskel., 65: 955-963.

E. C. Raff, H. D. Hoyle, E. M. Popodi, and F. R. Turner. 2008. Axoneme beta-tubulin sequence determines attachment of outer dynein arms. Current Biology 18: 911-914.

Hoyle, H. D., F. R. Turner, and E. C. Raff. 2008. Axoneme-dependent tubulin modifications in singlet microtubules of the Drosophila sperm tail.  Cell Motil. Cytoskel.  65: 295–313 (2008)

Raff E. C., Villinski, J.T., Turner, F.R., Donoghue, P. and R.A. Raff.  2006.  Experimental taphonomy shows the feasibility of fossil embryos.  PNAS 103: 5846-5851. 

Hagadorn, J.W., S. Xiao, P. C. J. Donoghue, S. Bengtson, N. J. Gostling, M. Pawlowska, E. C. Raff, R. A. Raff, F. R. Turner, Y. Chongyu, C. Zhou, X. Yuan, M. B. McFeely, M. Stampanoni, K. H. Nealson.  2006.  Cellular and Subcellular Structure of Neoproterozoic Animal Embryos.  Science 314: 291-294. 

Popodi, E. M., Hoyle, H.D., F. R. Turner, and E. C. Raff.  2005. The proximal region of the beta-tubulin C-terminal tail is sufficient for axoneme assembly.  Cell Motil. Cytoskel. 62: 48-64.

Sarpal, R., S. V. Todi, E. Sivan-Loukianova, S. Shirolikar, N. Subramanyan, E. C. Raff, J. W Erickson, K. Ray, and D. F. Eberl.  2003.  Drosophila Kinesin Associated Protein (DmKap) interacts with the Kinesin II motor subunit Klp64D to assemble chordotonal sensory cilia but not sperm.  Current Biology 13: 1687-1696.

Raff, E.C., V. B. Morris, E. M. Popodi, J. S. Kauffman, B. J. Sly, R. Turner, and R. A. Raff.  2003.  Regulatory punctuated equilibrium in the evolution of developmental pathways in direct-developing sea urchins.  Evolution & Development 5: 478–493. 

Nielsen, M.G, and E.C. Raff.  2002.  The best of all worlds or the best possible world?  Developmental constraint in the evolution of beta tubulin and the sperm tail axoneme.  Evolution & Development 4: 303-315.

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