Dr. Bettina Schmid
The Fish Core Facility is associated to Prof. Dr. Haass chair
German Center for Neurodegenerative Diseases (DZNE)
+49 (0) 89 / 218075-451
+49 (0) 89 / 218075-415
|Frauke van Bebber, Ph.D., Postdoc||+49 (0)89/2180-75490||+49 (0)89/2180-75415|
|Alexander Hruscha, Technical Assistant||+49 (0)89/2180-75444||+49 (0)89/2180-75415|
|Esau Roberto Rojas Rojas, Animal Keeper||+49 (0)89/2180-75444||+49 (0)89/2180-75415|
|Further group members (LMU/third party funding)|
|Barbara Solchenberger, Ph.D. student||+49 (0)89/2180-75490||+49 (0)89/2180-75415|
|Laura Hasenkamp, Ph.D. student||+49 (0)89/2180-75490||+49 (0)89/2180-75415|
|Katrin Strecker, Ph.D. student||+49 (0)89/2180-75490||+49 (0)89/2180-75415|
Dr. Bettina Schmid studied Biology in Hohenheim, Corvallis (Oregon, USA), and Tübingen where she graduated in 1996. During her diploma work she collected the first experiences with zebrafish in the lab of Prof. Christiane Nüsslein-Volhard. She then moved to the University of Pennsylvania (USA) (Prof. Mullins) for her PhD and graduated in 1999. After a Postdoc at Harvard Medical School (USA) with Prof. Len Zon she returned for two more years back to the Max-Planck Institute of Developmental Biology (Prof. Nicolson) in Tübingen. From 2003 until 2009 she was as a junior group leader at the Ludwig-Maximilians-Unversität in the Department of Prof. Christian Haass. She established a Zebrafish faclity and a research group focussing on neurodegenerative diseases in Zebrafish.
She has been the leader of the Zebrafish Core Facility of the DZNE since November 2009.
Parkin is protective against proteotoxic stress in a transgenic zebrafish model.
Fett ME, Pilsl A, Paquet D, van Bebber F, Haass C, Tatzelt J, Schmid B, Winklhofer KF, PLoS One. 2010 Jul 30;5(7):e11783.
ALS-associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear import.
Dormann D, Rodde R, Edbauer D, Bentmann E, Fischer I, Hruscha A, Than ME, Mackenzie IR, Capell A, Schmid B, Neumann M, Haass C, EMBO J. 2010 Aug 18;29(16):2841-57. Epub 2010 Jul 6.
Methylene blue fails to inhibit Tau and polyglutamine protein dependent toxicity in zebrafish.
van Bebber F, Paquet D, Hruscha A, Schmid B, Haass C, Neurobiol Dis. 2010 Sep;39(3):265-71. Epub 2010 Apr 8.
Transgenic zebrafish as a novel animal model to study tauopathies and other neurodegenerative disorders in vivo.
Paquet D, Schmid B, Haass C, Neurodegener Dis. 2010;7(1-3):99-102. Epub 2010 Feb 18.
Neprilysin activity in cerebrospinal fluid is associated with dementia and amyloid-β42 levels in Lewy body disease.
W Maetzler, V Stoycheva, B Schmid, C Schulte, AK Hauser, K Brockmann, A Melms, T Gasser, D Berg; J Alzheimers Dis. 2010 Jan 1;22(3):933-8.
A zebrafisch model of tauopathy allows in vivo imaging of neuronal cell death and drug evaluation.
Paquet D., Bhat R., Sydow A., Mandelkow E., Distel M., Köster R., Schmid B. and Haass C. (2009), J. Clinical Investigation, 119, 1382 - 1395.
Missense mutations in the progranulin gene linked to frontotemporal lobar degeneration with ubiquitin-immunoreactive inclusions reduce progranulin production and secretion.
Shankaran, S.S., Capell, A., Hruscha, A.T., Fellerer, K., Neumann, M., Schmid, B., and Haass, C. (2008), J. Biol. Chem. 283, 1744-1753
montalcino, A zebrafish model for variegate porphyria.
Dooley KA, Fraenkel PG, Langer NB, Schmid B, Davidson AJ, Weber G, Chiang K, Foott H, Dwyer C, Wingert RA, Zhou Y, Paw BH, Zon LI; Tübingen 2000 Screen Consortium, Exp Hematol. 2008 Sep;36(9):1132-42.
Identification of anti-prion compounds as efficient inhibitors of polyglutamine protein aggregation in a zebrafish model.
Schiffer, N.W., Broadley, S.A., Hirschberger, T., Tavan, P., Kretzschmar, H.A., Giese, A., Haass, C., Hartl, F.U. and Schmid, B, (2007) J Biol Chem 282, 9195-203.
Loss-of-function of human PINK1 results in mitochondrial pathology and can be rescued by parkin.
Exner N, Treske B, Paquet D, Holmström K, Schiesling C, Gispert S, Carballo-Carbajal I, Berg D, Hoepken HH, Gasser T, Krüger R, Winklhofer KF, Vogel F, Reichert AS, Auburger G, Kahle PJ, Schmid B, Haass C, J Neurosci. 2007 Nov 7;27(45):12413-8.
Deficiency of glutaredoxin 5 reveals Fe-S clusters are required for vertebrate haem synthesis.
Wingert RA, Galloway JL, Barut B, Foott H, Fraenkel P, Axe JL, Weber GJ, Dooley K, Davidson AJ, Schmid B, Paw BH, Shaw GC, Kingsley P, Palis J, Schubert H, Chen O, Kaplan J, Zon LI; Tubingen 2000 Screen Consortium, Nature 436(7053):1035-39 (2005)
Differential localization and identification of a critical aspartate suggest non-redundant proteolytic functions of the presenilin homologues SPPL2b and SPPL3.
Krawitz P, Haffner C, Fluhrer R, Steiner H, Schmid B, Haass C, J Biol Chem. 280(47) (2005) :39515-23
Maternally supplied smad5 is required for ventral specification in zebrafish embryos prior to zygotic bmp signaling.
Kramer C, Mayr T, Nowak M, Schumacher J, Runke G, Bauer H, Wagner D, Schmid B, Imai Y, Talbot W, Mullins M, Hammerschmidt M, Dev Biol. 250(2) (2002):263
Cooperative action of ADMP- and BMP-mediated pathways in regulating cell fates in the zebrafish gastrula.
Willot V, Mathieu J, Lu Y, Schmid B, Sidi S, Yan YL, Postlethwait JH, Mullins M, Rosa F, Peyrieras N, Dev Biol. 241(1) (2002):59-78
Genetic analysis of melanophore development in zebrafish embryos.
Kelsh RN, Schmid B, and Eisen J, Dev. Biol. 225 (2000),277-293
Equivalent genetic roles for bmp7/snailhouse and bmp2b/swirl in dorsoventral pattern formation.
Schmid B, Fürthauer M, Connors SA, Trout J, Thiesse B, Thisse C, and Mullins MC, Development 127 (2000), 957-967(2000)
Ventral and lateral regions of the zebrafish gastrulae, including the neural crest progenitors, are established by a bmp2b pathway of genes.
Vu H. Nguyen, Bettina Schmid, Jamie Trout, Stephanie A. Connors, Mark Ekker, and Mary C. Mullins, Dev. Biol. 199 (1998), 93-110
A gradient of cytoplasmic Cactus degradation establishes the nuclear localization gradient of the dorsal morphogen.
Andreas Bergmann, David Stein, Robert Geissler, Susanne Hagenmeier, Bettina Schmid, Nielsen Fernandez, Beate Schnell, Christiane Nüsslein-Volhard, Mech. of Dev. 60 (1996), 109-123
Areas of investigation/research focus
Our group uses the advantages of the zebrafish, Danio rerio, as an in vivo model system to address some of the unresolved questions in Alzheimer’s disease, Parkinson’s disease, Frontotemporal Lobar Degeneration (FTLD), and Amyotrophic lateral Sclerosis (ALS). Our research has four major aims:
- 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.
- 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.
- 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 image neuronal cell death in Tg(HuC:TauP301L) larvae in vivo.
- 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.
The cooperation partner's homepage can be found here.