Download CESR5 Epigenetic regulation of MeCP2 using IPSC

Application Code: CESR5
Epigenetic regulation of MeCP2 using IPSC-derived neural cells generated from patients with Rett
syndrome
One ESR Marie Curie training position is available at the Center for Neurogenomics and Cognitive
research (www.cncr.nl) VU University Amsterdam in the teams of Danielle Posthuma, Sophie van der
Sluis, and Vivi Heine, within the Innovative Doctorate Program CognitionNet
([email protected]).
Responsibilities and tasks
Rett syndrome is a progressive neurological disorder, diagnosed under the pervasive developmental
disorders, affecting 1 in 10,000 girls. It is characterized by an initial period of seemingly normal postnatal development, up until 6-18 months, after which it is followed by an increasing manifestation of
symptoms. These include deceleration in growth, loss of acquired motor and language skills,
characteristic hand-writhing movements, muscle hypotonia, breathing problems and cognitive
impairment. There is no cure or therapy to ease symptoms.
Rett syndrome is caused by mosaic expression of mutant copies of the X-linked MECP2 gene. MeCP2 is
a protein that binds to methylated DNA throughout the genome and is thought to be involved in
epigenetic regulation of target gene expression. Understanding how MeCP2 regulates gene expression
and which target genes are most relevant for Rett syndrome will provide crucial mechanistic insight into
the etiology of Rett syndrome. The main goal of the current project is to identify the target genes of
MeCPs and investigate the regulatory function of MeCP2 using hIPSC derived cells from Rett patients
and healthy controls.
To reach this goal we have the following three objectives:
- generate hIPSC derived neural cells from Rett patients and healthy controls
- perform oxidative bisulfite sequencing of 5-methylcytosine and 5-hydroxymethylcytosine
- conduct a GWAS for expression levels across different phases of development
Qualifications
At the date of appointment, candidates must have obtained, or finalize within 5 months, a Master's
(M.Sc.) degree in Neuroscience, or a similar degree with an academic level equivalent to the Master's
degree in Neuroscience. For selection of the applicant we will look into the relevance of the applicant’s
research to the doctoral program he or she is applying for, earlier research achievements, and the
motivation letter. Solid written and oral communication skills in English are prerequisites of any
successful application.
Profile
• Master’s degree (or equivalent) Neuroscience, preferably in a field related to molecular neurobiology
• Previous lab experience in cell culture and molecular biology
• Interest to learn/apply behavioral studies related to cognition in general, and Rett syndrome in particular
• A good command of English language.