Claire Benard PhD
|Institution||University of Massachusetts Medical School|
|Address||University of Massachusetts Medical School|
364 Plantation Street, LRB
Worcester MA 01605
|Institution||UMMS - Graduate School of Biomedical Sciences|
|Department||Interdisciplinary Graduate Program|
|Institution||UMMS - Graduate School of Biomedical Sciences|
Claire Bénard received her Ph.D. (2003) from the Department of Biology of McGill University, Canada, supported by pre-doctoral scholarships from the Canadian funding agencies NSERC and FCAR. She obtained fellowships from the Natural Sciences and Engineering Research Council of Canada and from the Canadian Institutes of Health Research for her postdoctoral training at Columbia University in New York in the laboratory of Oliver Hobert. She joined the Department of Neurobiology at the University of Massachusetts Medical School as a faculty member in August 2009.
Please click the following link to view a Podcast about our research recorded at the Boston Museum of Science in May 2010. http://www.mos.org/events_activities/podcasts&d=4484
Maintenance of nervous system architecture: making it is not good enough
Our research goal is to elucidate how the architecture of the nervous system is maintained throughout the life of an animal. Neuronal structures established early in development, including organized ganglia, axon fascicles, dendrite bundles, and synapses, need to persist throughout adulthood for proper brain function. This poses a serious challenge to the nervous system as an animal dramatically increases its body size, remodels parts of its anatomy and incorporates new neurons. In addition, body movements, injury and ageing exert physical stress on the nervous system, which also compromise nervous system maintenance.
We use the nematode C. elegans as a model system to study the cellular and molecular bases of maintenance of neuronal architecture. The powerful molecular genetic methods that can be used in C. elegans, the transparency and the simplicity of the animal, the ease of observation from early stages to advanced adulthood, and the detailed knowledge of its anatomy, make the worm particularly suitable for addressing these questions. Using genetic analysis, molecular genetics, electron microscopy and biochemistry, we have shown that not only axons are actively maintained in their precise position along fascicles (Aurelio et al., 2002; Bülow et al., 2004), but also neuronal cell bodies in ganglia, and dendritic bundles, are maintained after their development is completed (Bénard et al., 2006; Figure 1). Failure to maintain neuronal architecture has detrimental functional consequences as adult mutants have behavioral deficits. Some defects arise at critical times during the life of the animal, while others progressively worsen.
The molecules implicated to date in neuronal maintenance display great molecular diversity of size and domain composition (Figure 2 ). Maintenance factors include the two-immunoglobulin domain protein ZIG-4 (Aurelio et al., 2002), the FGF receptor EGL-15(5A) (Bülow et al., 2004), the giant multidomain extracellular protein DIG-1 (Bénard et al., 2006) and the L1 CAM homologue SAX-7 (Pocock et al., 2008). Our current working model is that these neuronal maintenance factors, interact in different, cell-type-specific combinations to build adhesive complexes that anchor neurons and their projections to their environment. A balance of diverse and exquisite molecular interactions might maintain the nervous system's organization at the multicellular level.
We are currently taking a candidate gene and classic genetic approaches to identify new maintenance factors. We are pursuing the analysis of all zig genes, individually and in multiple mutant combinations, which like zig-4 encode two-immunoglobulin domains containing proteins. We find that all the zig genes function to bring about neuronal maintenance. We have also carried out an unbiased forward genetic screen and have identified novel maintenance genes, whose molecular identification will shed light on the mechanism of maintenance. We are also studying the interactions among the identified maintenance factors, by using a combination of genetic, biochemical and biophysical approaches to address questions such as: What are the roles of the ZIG proteins? Do the ZIG and SAX-7 proteins interact? How is the maintenance of specific neurons mediated?
Our research will enhance our understanding of neuronal maintenance mechanisms, as well as how proteins containing such evolutionarily conserved domains function. Given the striking evolutionary conservation of genes that control neural development and function from worm to human, our studies will likely be relevant to the maintenance of neuronal architecture in the vertebrate nervous system as well. Moreover, it is conceivable that some neurodegenerative diseases, for which the causes are unknown, may result from failures in neuronal maintenance mechanisms.
The Bénard lab studies how the architecture of the nervous system is maintained throughout the life of an animal. Neuronal structures established early in development need to persist throughout adulthood for proper brain function. We use the nematode C. elegans as a model system to elucidate the cellular and molecular bases of maintenance of neuronal architecture. Some neurodegenerative diseases for which the causes are unknown may result from postdevelopmental failures in these maintenance mechanisms.
Rotation projects include the study of the genetic and biochemical interactions of three identified maintenance factors. Students will get training in genetics, molecular genetics and biochemical approaches and will use a range of molecular biology, cell culture, microscopy and genetic techniques. Contact the lab to discuss specific interests and projects.
Postdoctoral candidates interested in research on brain development and maintenance are welcome to apply. For starting in September 2010 or later. Contact Dr. Claire Bénard (Email: Claire.Benard@umassmed.edu).
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