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Investigating synaptogenesis in iPSC-derived neurons from ADHD patients after Methylphenidate treatment
Our lab is looking for a highly motivated Bachelor/Master student, who is interested to conduct a research in the field of disease modeling using ADHD patient-specific cells. The process will involve learning how to generate and culture human induced pluripotent stem cells (iPSCs) and generation of neural stem cells (NSCs) from patients with Attention-Deficit Hyperactivity Disorder (ADHD), as well as how to scientifically interpret and discuss scientific papers and conduct research with independence and critical thinking.
Keywords: ADHD, Methylphenidate, synaptogenesis, immunocytochemistry, iPSCs, NSCs, neurons, Wnt pathway, Western blot
Attention-deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental behavioral disorders. It consists of a multifactorial disorder, in which genetics play an important role in etiology, as well as environmental factors. One of the treatments of choice for ADHD is the pharmacological treatment with Methylphenidate (MPH; commercially known as Ritalin). This drug seems to ameliorate the structural and functional brain maturational delays that are commonly found in ADHD patients. However, the cellular and molecular mechanisms underlying this process are still not fully elucidated. At the same time, the Wnt signaling has been described as one of the pathways involved in ADHD, being important during neurodevelopment and for orchestrating essential cellular processes, such as maturation, proliferation and synaptogenesis. The use of iPSCs has been a powerful tool to the research of neuropsychiatric disorders, as animal models cannot fully recapitulate clinical conditions and the polygenic profile of human patients and neuroimaging studies cannot investigate molecular mechanisms of living functional cells from a human Central Nervous System. In this project, you would be able to investigate a neuronal phenotype by performing immunocytochemistry (ICC). For further quantification of synapses using ICC, iPSC-derived NSCs will be chronically treated with MPH throughout neuronal differentiation. Moreover, the expression of Wnt-related proteins after chronic treatment will also be investigated.
Attention-deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental behavioral disorders. It consists of a multifactorial disorder, in which genetics play an important role in etiology, as well as environmental factors. One of the treatments of choice for ADHD is the pharmacological treatment with Methylphenidate (MPH; commercially known as Ritalin). This drug seems to ameliorate the structural and functional brain maturational delays that are commonly found in ADHD patients. However, the cellular and molecular mechanisms underlying this process are still not fully elucidated. At the same time, the Wnt signaling has been described as one of the pathways involved in ADHD, being important during neurodevelopment and for orchestrating essential cellular processes, such as maturation, proliferation and synaptogenesis. The use of iPSCs has been a powerful tool to the research of neuropsychiatric disorders, as animal models cannot fully recapitulate clinical conditions and the polygenic profile of human patients and neuroimaging studies cannot investigate molecular mechanisms of living functional cells from a human Central Nervous System. In this project, you would be able to investigate a neuronal phenotype by performing immunocytochemistry (ICC). For further quantification of synapses using ICC, iPSC-derived NSCs will be chronically treated with MPH throughout neuronal differentiation. Moreover, the expression of Wnt-related proteins after chronic treatment will also be investigated.
The goal of this project is to investigate whether chronic MPH treatment modulates the synaptic connectivity in ADHD neurons through the Wnt signaling pathway.
The goal of this project is to investigate whether chronic MPH treatment modulates the synaptic connectivity in ADHD neurons through the Wnt signaling pathway.
Requirements:
The student must be registered as a master student in an acknowledged University during the period of the project. The master thesis project will be as part of the requirements of their master degree.
Previous experience in mammalian cell culture and/or basic molecular biology methods would be desired, but not strictly necessary.
You learn
• Generation and culture techniques of iPSCs, NSCs and neurons
• Quality control techniques, such as: immunocytochemistry, mycoplasma testing, DNA/RNA extraction, RT-qPCR
• Immunocytochemistry assays and confocal microscopy imaging
• Western blot
• Data analysis
• Critical thinking and independence on conduct their own project
• How to effectively work in a team
Prof. Edna Grünblatt; Translational Molecular Psychiatry, Department of Child and Adolescent Psychiatry and Psychotherapy (KJPP), Psychiatric University Hospital Zurich (PUK); edna.gruenblatt@kjpd.uzh.ch; https://www.kjpd.uzh.ch/de/translationale-molekularpsychiatrie.html
Requirements: The student must be registered as a master student in an acknowledged University during the period of the project. The master thesis project will be as part of the requirements of their master degree. Previous experience in mammalian cell culture and/or basic molecular biology methods would be desired, but not strictly necessary. You learn • Generation and culture techniques of iPSCs, NSCs and neurons • Quality control techniques, such as: immunocytochemistry, mycoplasma testing, DNA/RNA extraction, RT-qPCR • Immunocytochemistry assays and confocal microscopy imaging • Western blot • Data analysis • Critical thinking and independence on conduct their own project • How to effectively work in a team
Prof. Edna Grünblatt; Translational Molecular Psychiatry, Department of Child and Adolescent Psychiatry and Psychotherapy (KJPP), Psychiatric University Hospital Zurich (PUK); edna.gruenblatt@kjpd.uzh.ch; https://www.kjpd.uzh.ch/de/translationale-molekularpsychiatrie.html