Erives Lab
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Lab: 603.646.1532
Fax: 603.646.1541
"However clever you
think cells are,
They are clever!"
of the 40th anniversary of his
Positional Information model
in a special session on
morphogen gradients.
Gordon Research Conference:
Developmental Biology
Andover, New Hampshire
June 24th, 2009
Albert J. Erives
Dept. of Biological Sciences
Dartmouth College
Our lab works on the biology of genomes, including their structure, function, and evolution. We are investigating the extent to which complex gene regulation is encoded by three distinct usages of binding site motifs: 1) motif lexicon (combination of sequence elements for signal integration); 2) motif grammar (specific sequence usage for concentration threshold-specific binding, or for allosteric induction); and 3) motif syntax (precise orientation and positioning of sequence elements for specificity). We have several projects and collaborations in regulatory and evolutionary genomics.
REGULATORY GENOMICS:
- Mechanisms of gene regulation
- Classification and enumeration of types of regulatory DNA modules (RDMs)
- Genome structure and function
EVOLUTIONARY GENOMICS:
- Origin and diversification of particular eukaryotic regulons
- Role of the bHLH family in early metazoan evolution
- Evolution of the human genome
RECENT PROJECTS:
Evolution of readouts of the Dorsal morphogen gradient system of Drosophila
Morphogen gradients provide important long-range patterning mechanisms to developing organisms. Specifically, morphogen gradients allow different genes to respond to specific levels of a morphogen, and thereby to infer the cell's position in the multi-cellular body. In order to better understand how this is accomplished, we have been studying a set of transcriptional enhancers that have evolved at unrelated genomic loci expressed in the ventral regions of the neurogenic ectoderm. These neuroectodermal enhancers share in common a set of motifs in a distinctive arrangement. By definition, we have called sequences matching this unique profile Neurogenic Ectoderm Enhancers (NEEs). We have experimented with over 25 NEEs from D. melanogaster, D. ananassae, D. willistoni, D. pseudoobscura, D. virilis, and Anopheles gambiae. So far, every NEE sequence we have identified and assayed is sensitive to a specific threshold concentration level of the Dorsal morphogen, which patterns the dorsal/ventral (D/V) axis in dipteran embryos. These results show that the relative organization (i.e. position and orientation) of binding sites for Dorsal and its targeted co-activators are key determinants in reading out position along the D/V axis.Evolution of the RTK > Myc/Max > ribosome biogenesis growth switch
Comparative regulatory genomics provides a powerful approach for identifying the nature and evolutionary origins of cell signaling pathways. Using these techniques, we have been able to identify and document the evolutionary birth of a growth switch in the latest common ancestor of metazoans and choanoflagellates. We have shown that this holozoan ancestor evolved critical components of an important growth signaling pathway that includes: Receptor Tyrosine Kinases (RTKs); Myc/Max bHLH heterodimer complexes; and Myc/Max binding sites in the core promoters of ribosome biogenesis (RiBi) genes, whose products function in the nucleolus. We also show that Myc/Max alone, but neither Mad/Max nor Mnt/Max, is responsible for evolutionary maintenance of the Myc/Max binding site at the core promoters of RiBi genes. Interestingly, we have also demonstrated that nematodes, which are small-bodied metazoans, have secondarily lost both the myc gene and Myc/Max binding sites in RiBi core promoters. We propose that this is a direct consequence of a body plan composed of 1000 somatic cells and the deprecated need for inducible, accelerated rates of protein synthesis associated with rapidly proliferating cell populations, which is a common feature of large-bodied metazoans.
Last modified June 18th, 2009.
