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Oliver  Hobert
Oliver Hobert
Professor of Biochemistry and Molecular Biophysics


Address: Fairchild Building Room 805 New York NY 10027
Phone: (212) 853-0063
Fax:
E-mail:

or38@columbia.edu

Education and Training:
Ph.D. 1995, Max Planck Institute for Biochemistry
Postdoctoral Fellow 1996-1999, Harvard Medical School
Affiliations:
bullet  Department of Biological Sciences
bullet  Howard Hughes Medical Institute
Training Activities:
bullet  Department of Genetics and Development
Research Summary:
(800 words, max)
Genetic programs that control neural development in C. elegans
Current Research:
The focus of the lab is the study of the molecular mechanisms that lead to the generation of specific neural circuits in the brain, which in turn subserve specific behaviors. We are interested in the developmental aspect of neural circuit generation as well as later aspects of maintenance and modification of neural circuits, which presumably are the basis of learning and memory processes. Due to the complexity of the vertebrate brain, we use the much simpler nervous system of the nematode C.elegans as a model system. The completely sequenced genome of C.elegans as well as its amenability to classical genetic methods allow the identification of molecules that are required for the neural differentiation and the generation of specific neural circuits. We have focused our interests on 4 different areas, each of which constitutes an important aspect in the development and functioning of neural circuits.

1) Neuronal patterning: Here, we focus on studying a particular exciting step of neural development, the induction of left/right bilateral asymmetry in the brain. We have identified a homeobox gene that is asymmetrically expressed in the brain of C.elegans and have conducted mutant screens for genes that are required to establish this asymmetry. We have identified the molecular nature of these genes and uncovered a novel signaling pathway.

2) Neuronal differentiation: We have identified a set of putative target genes of a homeobox gene, ttx-3, which we had previously shown to be required for terminal differentiation of an interneuron class in the brain of C.elegans. We are investigating the function of these target genes, one of which is a cell-surface bound protein related to a human disease gene, using both forward and reverse genetic approaches. We also dissect the promoters of these target genes in order to identify the target sites for the homeodomain protein and to understand the molecular logic of transcriptional control in the nervous system.

3) Maintenance of neuronal features: In a reverse genetic approach, we made use of the completed genome sequence of C.elegans and found a novel class of Ig domain proteins that is required for the maintenance of ventral nerve cord organization. We also undertook genetic screens to identify molecules that are required for retrograde signaling from a target cell (muscle or neuron) to its presynaptic neuron target to ensure the maintenance of an intact neuronal morphology.

4) Behavior: The above mentioned research areas deal with aspects of neural circuit development and maintenance, but not with function per se. Several of the target genes that we identified for the homeobox gene ttx-3 are excellent candidates for subserving specific roles in neural circuit functioning and possibly plasticity. We have established a simple behavioral assay to test this possibility.
Publications:
(6 max)
1. Hobert, O.: (2005) MicroRNAs: all gone and then what?.  Curr. Biol  15(10): R387-389

2. Hobert, O.: (2004) Common logic of transcription factor and microRNA action.  Trends Biochem Sci  29(9): 462-468

3. Bülow, H.E., Boulin, T., Hobert, O.: (2004) Differential Functions of the C. elegans FGF Receptor in Axon Outgrowth and Maintenance of Axon Position.  Neuron  42(3): 367-374

4. Wenick AS, Hobert O.: (2004) Genomic cis-regulatory architecture and trans-acting regulators of a single interneuron-specific gene battery in C. elegans.  Developmental Cell  6(6): 757-770

5. Chang S, Johnston RJ Jr, Frokjaer-Jensen C, Lockery S, Hobert O. : (2004) GenoMicroRNAs act sequentially and asymmetrically to control chemosensory laterality in the nematode .  Nature  430(7001): 785-789

6. Hobert, O., Hutter, H., Hynes, R.O. : (2004) The immunoglobulin superfamily in Caenorhabditis elegans and Drosophila melanogaster.  Development  131(10): 2237-2238

URL for lab page:
 http://cumc.columbia.edu/dept/gsas/biochem/labs/hobert/

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