Post Doctoral Fellowships
Karen Monier, Ph.D.
The Scripps Research Institute
"Role of MeCP2 in the formation of centric heterochromatin compartments in neurons."
Mentor: Kevin F. Sullivan, Ph.D.
2-Year Award: $90,000
Lay Progress Report (August 2001)
One of the most important issues to start figuring out what is wrong in brain cells of Rett patients is being able to discriminate the sick cells expressing the bad MeCP2 gene from the healthy cells that express the normal MeCP2 gene. For that purpose, I suggest to combine the use of two different labels to detect under the microscope the healthy cells and the sick cells. I showed promising preliminary results that might be applicable to detect sick cells from Rett patients expressing a protein truncated at one of its end (C-terminus: 70 % of the Rett cases). This approach will allow the determination of the percentage of sick cells in different regions of Rett patients brains and more importantly comparison of the structure of their central unit, the nucleus. Defaults of specific compartments or organization of their nucleus will bring new insights into the potential role of MeCP2 during Rett child development. Another critical issue, to study the steps a brain cell goes through to mature properly, is to find a cellular model that can be used to study what's going on when a cell becomes a neuron during development. During my first year of research, I used an embryonic cell line (called NT2) to study how and what dramatic structural changes occur in their central unit, the nucleus, when those cells were forced to become brain cells. I observed changes that are known to happen during this programming process (like an increased nuclear size), as well as new structural modifications, not described before. The most interesting one, directly related to the Rett disease, is that the potential binding sites for MeCP2 (methylated DNA) are completely redistributed in the nucleus of those reprogrammed brain cells. This observation would support our leading hypothesis that new compartments are formed in the nucleus of brain cells to shut down genes that are not any more desirable to be expressed in those cells. Another interesting observation, permitted the establishment of a new link between the potential binding sites for MeCP2 and a specific category of modifications that affect proteins essential in the structure of the nucleus (histones). Understanding what are the structural changes involve during the programming of a cell into a brain cell will certainly bring new insights into the role played by MeCP2 during brain development.
Karen Monier, Ph.D.The Scripps Research Institute
"Role of MeCP2 in the formation of centric heterochromatin compartments in neurons."
Mentor: Kevin F. Sullivan, Ph.D.
2-Year Award: $90,000
Lay Progress Report (August 2001)
One of the most important issues to start figuring out what is wrong in brain cells of Rett patients is being able to discriminate the sick cells expressing the bad MeCP2 gene from the healthy cells that express the normal MeCP2 gene. For that purpose, I suggest to combine the use of two different labels to detect under the microscope the healthy cells and the sick cells. I showed promising preliminary results that might be applicable to detect sick cells from Rett patients expressing a protein truncated at one of its end (C-terminus: 70 % of the Rett cases). This approach will allow the determination of the percentage of sick cells in different regions of Rett patients brains and more importantly comparison of the structure of their central unit, the nucleus. Defaults of specific compartments or organization of their nucleus will bring new insights into the potential role of MeCP2 during Rett child development. Another critical issue, to study the steps a brain cell goes through to mature properly, is to find a cellular model that can be used to study what's going on when a cell becomes a neuron during development. During my first year of research, I used an embryonic cell line (called NT2) to study how and what dramatic structural changes occur in their central unit, the nucleus, when those cells were forced to become brain cells. I observed changes that are known to happen during this programming process (like an increased nuclear size), as well as new structural modifications, not described before. The most interesting one, directly related to the Rett disease, is that the potential binding sites for MeCP2 (methylated DNA) are completely redistributed in the nucleus of those reprogrammed brain cells. This observation would support our leading hypothesis that new compartments are formed in the nucleus of brain cells to shut down genes that are not any more desirable to be expressed in those cells. Another interesting observation, permitted the establishment of a new link between the potential binding sites for MeCP2 and a specific category of modifications that affect proteins essential in the structure of the nucleus (histones). Understanding what are the structural changes involve during the programming of a cell into a brain cell will certainly bring new insights into the role played by MeCP2 during brain development.