Cell-based screening of epidrugs for MECP2 reactivation

A call is open for 1 PhD student position in the field of X-inactivation research and pharmacological approach for Rett syndrome, at the Institute of Genetics and Biophysics- National Research Council of Italy (IGB-CNR), in Naples (http://www.igb.cnr.it/incipit/supervisors/files/2017/Vacca.pdf).
The duration of the contract is 36 months (or 12 Months renewable up to 36 months).
This position is within the frame of INCIPIT, an international PhD programme, which aims at providing innovative multidisciplinary and intersectoral training in Life and Biomaterial Sciences.

INCIPT PhD programme includes:
^laboratory activities to carry out doctoral research projects;
^theoretical courses run by the Doctoral Schools of the Second University of Naples (SUN),
the University of Naples Federico II and the University of Catania (UNICT);
^activities related to transferable skills.

Project Description
Rett Syndrome (RTT) is an X-linked neurodevelopmental disorder caused by mutation in the MECP2 gene.
Heterozygous female patients are a somatic mosaic of two populations of cells due to X chromosome inactivation (XCI), that silences one of the two X chromosomes in female mammals. In so, females tolerate X-linked mutations better than males, having a WT allele expressed in a proportion of cells that equals to 50%, if XCI occurs randomly and the mutant cells do not present any advantage or disadvantage in survival. The severity of RTT varies with the proportion of cells expressing the WT or the mutant MECP2, depending on XCI patterns in heterozygous females. Reversibility of XCI has been recently shown in somatic cells. Therefore, it is theoretically possible to re-activate the WT XCI-silenced allele of a mutant gene to counteract the pathological phenotype. Re-expression of the protein in Mecp2-null mice with symptoms of Rett can reverse the neurological defects. Accordingly, approaches to reactivate the endogenous WT copy of the MECP2 gene in heterozygous human patients with RTT might provide a potential avenue to treat this disease.
Our experimental strategy consists in cell-based screening of epidrugs for MECP2 reactivation.

Job description
Th PhD project is mainly composed of 2 phases: (i) development of a reactivation assay based on a dual color reporter system and suitable for automation; (ii) Pilot screening of epigenetic compounds libraries to identify molecules effective in Xi-reporters reactivation.

Candidate skills
We are looking for a curious, independent and creative early stage researcher with strong background and interests in molecular or cellular biology. The fellow will work in a young and scientifically stimulating environment.
Applicants should have a master degree in Life or Natural sciences (e.g. Biology, Biochemistry, Biotechnology, Molecular Biology, or related fields), corresponding to the second level of studies. Preference will be given to candidates with a strong background and interest in Molecular or Cellular biology. Knowledge of the mammalian X inactivation process will be appreciated.