Thesis supervisor: András Dinnyés
Location of studies (in Hungarian): BioTalentum Ltd Abbreviation of location of studies: BioT
Description of the research topic:
Appropriate assessment of ASO safety and neurotoxicity is an important innovative component of preclinical tailored ASO treatment development, ensuring rapid preclinical development and reducing use of animal experiments. To facilitate timely development of effective and safe ASOs, the use of human iPSC-derived neural models that phenocopy the biochemical pathways in human cells is crucial (PMID: 29909083). Approach: We will use control human iPSCs-derived neuronal 2D and 3D cultures that can recapitulate the biochemical pathways, supportive function and excitability patterns characteristic of mature CNS cells. A. For 2D cultures, iPSC will be differentiated into frontal cortical neurons and astrocytes. B. 3D neuronal spheroids will be differentiated into matured neural organoids. For immune responses, the 3D models can be enriched with microglia. Using Biotalentum’s well-established drug discovery platforms, sensitive assays will be developed including structural and functional aspects of neuronal vulnerability (biomarkers for membrane damage, apoptotic pathway commitment, mitochondrial depolarization, action potential activity and calcium oscillations) as well as neurite outgrowth, morphological changes, gene expressions changes and functional analyses such as electrical activities, mitochondrial fragmentation and oxidative stress responses (PMID: 30233290). C. These in vitro ASO safety assessment assays will be linked to the in vivo safety studies within the consortium, allowing cross-validate in vitro and in vivo methodology and improving the identification of ASOs with potential safety and toxicity risks.
Required language skills: English Further requirements: "Researchers must hold a degree in biology/ biotechnology that qualifies them to begin a PhD and be enrolled as a PhD student (usually Master’s /MSc/ degree or comparable).
Deadline for application: 2024-05-31
2024. IV. 17. ODT ülés Az ODT következő ülésére 2024. június 14-én, pénteken 10.00 órakor kerül sor a Semmelweis Egyetem Szenátusi termében (Bp. Üllői út 26. I. emelet).
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