Master Thesis – Decoding AMD : A Comparative Transcriptomic Study of Human and Mouse Retina Organoids

The UFZ

The Helmholtz Centre for Environmental Research (UFZ) with its 1,100 employees has gained an excellent reputation as an international competence centre for environmental sciences. We are part of the largest scientific organisation in Germany, the Helmholtz association. Our mission : Our research seeks to find a balance between social development and the long-term protection of our natural resources.

The job

The master thesis explores species-specific responses to age-related macular degeneration (AMD) using human and mouse retina organoids. The study will leverage bulk RNA-Seq data to uncover molecular pathways affected by HBEGF-TNFa (HT) treatment across different developmental stages in both species. The treatment is designed to model AMD-like phenotypes such as photoreceptor degeneration, glial pathologies, dyslamination, and scar formation.

Recent work has provided detailed insights into the effects of HT treatment in human retina organoids, highlighting significant transcriptomic changes linked to AMD-like phenotypes. However, the mouse retina does not have a macula, leading to the question of whether the mouse is a relevant model for macular degeneration. Similarly, immune responses, genetic risk factors, and retinal aging differ significantly between species. These distinctions influence AMD development and therapeutic responses, underscoring the importance of identifying conserved and species-specific molecular mechanisms. By comparing human and mouse organoid models, this project seeks to refine our understanding of AMD pathology and the translational relevance of preclinical models.

This project offers a unique opportunity to investigate interspecies differences in AMD-like pathology, combining cutting-edge bioinformatics with a focus on translational relevance. By contrasting human and mouse models, you will contribute to refining our understanding of retinal disease modeling and advancing AMD research.

Your tasks

• Bioinformatic Workflow ImplementationProcess bulk RNA-Seq data to generate count matrices for human and mouse retina organoids.Conduct differential gene expression analyses to identify treatment-induced molecular changes in each species.
• Pathway and Gene Set Enrichment AnalysisPerform pathway enrichment and gene set analysis to uncover the biological processes and molecular pathways affected by HT treatment.Compare the activation of these pathways between human and mouse organoids, highlighting similarities and species-specific differences.
• Phenotypic and Molecular ComparisonsCorrelate transcriptomic changes with known phenotypic outcomes such as photoreceptor degeneration, glial pathologies, and scar formation.Analyze differential responses in human and mouse organoids to elucidate distinct mechanisms driving these phenotypic changes.

The position to prepare the Master's thesis is limited to 6 months and will be supervised at the site in Leipzig.

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