Olivier Lucas
- PhD Student
- email: lucas@montana.edu
- Click to see my CV (*.doc)
Current Research
The TATA Binding Protein (TBP) is one of the most conserved protein in Nature, from archea to humans. It recruits the basal transcription machinery required to induce gene expression at the promotor site. Nevertheless, the N-terminus of TBP (Nt-TBP) is specific to the vertebrate lineage (invertebrates have an unrelated N-terminus).
The lab developed a transgenic mouse lacking the vertebrate specific Nt-TBP . 97% of these mice die at mid gestation (10.5 days) but look totally normal before (heart beating, organs...). The 3% survivors grow up well and are fertile. Various indicators tell us that the rejection occurs at the placental interface. Other students the lab (Amy and Nikki) are doing some immunology, embryology and genetics to understand what is killing the placenta-embryo.
The most interesting (to me!) part of this protein is that it evolved with the first fishes -Vertebrates- (hagfish and lamprey) and has undergone strong purifying selection -ie: very conserved- since then. As fishes do not have chorionic placentas, we suppose that the Nt-TBP plays more fundamental roles in early fishes like hagfish. These roles are not manifested as "phenotypes" in our mutant mouse (i.e. these roles might be "backed-up" by redundant systems in higher vertebrates). We would like to identify protein-protein interaction involving Nt-TBP in hagfish using yeast two-hybrid screens. I have cloned the hagfish Nt-TBP ("bait" vector) and made hagfish cDNA "prey" librairies. Future studies might screen the Nt-TBP of hagfish with a mouse library, shark library... and vice versa, to uncover the robustness of the protein-protein interactions. I also hope to test the evolutionary roles of Nt-TBP in-vivo, by inter-specific gene swapping experiments.
