Final Activity Report Summary - DROSOPHILA TELOMERES (Drosophila Telomere Heterochromatin: Gene silencing and Telomere targeting)
The Marie Curie International Reintegration Grant (IRG) has been crucial not only to develop an interesting project that has already resulted in one high rank publication and a second one in preparation but also very important to consolidate the research position of the fellow. Having this grant has allowed me to start my own projects, which will consolidate in two PhD projects from my laboratory (one already started). The Marie Curie IRG funding has been fundamental to pay personnel at the first stages of the grant.
Scientifically, the research project has proved that the determinants of the telomere targeting of the Gag protein from the HeT-A telomere retrotransposon, have been conserved in spite a low level of sequence identity. These studies have also shown how the Gag proteins from Drosophila species 60 million years apart are able to recognise the telomeres of each of the studied cell types. All these results resulted in a high rank publication (Casacuberta et al. (2007) Proc. Nat. Acad. Sci. USA, 104, 8391-96).
We are also preparing a publication of which telomere components are important for controlling gene expression at the telomere array (composed of the telomere retrotransposons, HeT-A, TART and TAHRE) and not at the subtelomere domain. Moreover, we have obtained results that seem to indicate that not all Drosophila telomeres respond equally to same telomere regulators. We are currently working in establishing which are the molecular mechanisms responsible for the changes in gene expression that we have observed for the different telomere domains.
Finally, we are verifying the different protein complexes that have been isolated by creating stable transfected Drosophila Cell lines with the retrotransposon proteins used as baits. After verifying the authenticity of these complexes and their interactions with the telomere retrotransposon proteins, we will be able to better understand the relationship between the telomerase mechanism and the retrotransposon mechanism of telomere maintenance. We will also be able to propose a possible scenario of how the transition from telomerase to the retrotransposon telomere could have taken place in evolution.
Scientifically, the research project has proved that the determinants of the telomere targeting of the Gag protein from the HeT-A telomere retrotransposon, have been conserved in spite a low level of sequence identity. These studies have also shown how the Gag proteins from Drosophila species 60 million years apart are able to recognise the telomeres of each of the studied cell types. All these results resulted in a high rank publication (Casacuberta et al. (2007) Proc. Nat. Acad. Sci. USA, 104, 8391-96).
We are also preparing a publication of which telomere components are important for controlling gene expression at the telomere array (composed of the telomere retrotransposons, HeT-A, TART and TAHRE) and not at the subtelomere domain. Moreover, we have obtained results that seem to indicate that not all Drosophila telomeres respond equally to same telomere regulators. We are currently working in establishing which are the molecular mechanisms responsible for the changes in gene expression that we have observed for the different telomere domains.
Finally, we are verifying the different protein complexes that have been isolated by creating stable transfected Drosophila Cell lines with the retrotransposon proteins used as baits. After verifying the authenticity of these complexes and their interactions with the telomere retrotransposon proteins, we will be able to better understand the relationship between the telomerase mechanism and the retrotransposon mechanism of telomere maintenance. We will also be able to propose a possible scenario of how the transition from telomerase to the retrotransposon telomere could have taken place in evolution.