Lab
Schmid Lab
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Statement of Research Interest
Our group uses the advantages of the zebrafish, Danio rerio, as an in vivo model system to address some of unresolved questions in Alzheimer’s disease, Parkinson’s disease, Frontotemporal Lobar Degeneration (FTLD), and Amyotrophic lateral Sclerosis (ALS). Our research has four major aims:
1. Generation of transgenic zebrafish
Animal models are crucial in understanding disease mechanisms and to design therapeutic strategies. We generated a powerful Gal4-UAS based trangenesis vector system that allowed us to generate numerous transgenic zebrafish lines. Transgenic expression of human disease associated genes enables us to recapitulate hallmarks of the respective human disease in zebrafish.
2. Generation of knock-downs and mutants
Genes associated with neurodegenerative diseases are being investigated for their in vivo function in zebrafish. Interestingly, very little is known about the physiological function of genes such as TDP-43 - despite their well-established role in ALS and FTD. Manipulation of protein levels mediated by injection of antisense gripNAs and subsequent analysis of the generated phenotypes enable us to gain insight into their physiological function. Additionally mutations in disease relevant genes are currently established by zinc finger nuclease mediated genome editing.
3. In vivo imaging
One of the great advantages of the zebrafish is the optical transparency during early larval stages. This allows expression of fluorescent reporters and in vivo imaging at sub-cellular resolution. For example, we were able to in vivo image neuronal cell death in Tg(HuC:TauP301L) larvae.
4. Drug evaluation in disease models
The transgenic disease models generated are great tools to search for disease modifying drugs. Zebrafish larvae are small in size (< 1mm) and live in an aqueous environment where chemicals can be easily applied. Zebrafish therefore represent a wonderful tool to assay for disease modifying drugs in vivo.
1. Generation of transgenic zebrafish
Animal models are crucial in understanding disease mechanisms and to design therapeutic strategies. We generated a powerful Gal4-UAS based trangenesis vector system that allowed us to generate numerous transgenic zebrafish lines. Transgenic expression of human disease associated genes enables us to recapitulate hallmarks of the respective human disease in zebrafish.
2. Generation of knock-downs and mutants
Genes associated with neurodegenerative diseases are being investigated for their in vivo function in zebrafish. Interestingly, very little is known about the physiological function of genes such as TDP-43 - despite their well-established role in ALS and FTD. Manipulation of protein levels mediated by injection of antisense gripNAs and subsequent analysis of the generated phenotypes enable us to gain insight into their physiological function. Additionally mutations in disease relevant genes are currently established by zinc finger nuclease mediated genome editing.
3. In vivo imaging
One of the great advantages of the zebrafish is the optical transparency during early larval stages. This allows expression of fluorescent reporters and in vivo imaging at sub-cellular resolution. For example, we were able to in vivo image neuronal cell death in Tg(HuC:TauP301L) larvae.
4. Drug evaluation in disease models
The transgenic disease models generated are great tools to search for disease modifying drugs. Zebrafish larvae are small in size (< 1mm) and live in an aqueous environment where chemicals can be easily applied. Zebrafish therefore represent a wonderful tool to assay for disease modifying drugs in vivo.
Lab Members
| van Bebber, Frauke Post-Doc | Hasenkamp, Laura Graduate Student | Strecker, Katrin Graduate Student |
| Rojas, Roberto Rojas Fish Facility Staff | Hruscha, Alexander Technical Staff |