Search

Your search keyword '"Sterzenbach, Ulrich"' showing total 6 results
Start Over Author "Sterzenbach, Ulrich" Search Limiters Full Text
6 results on '"Sterzenbach, Ulrich"'

2. Engineered exosomes as carriers of biologically active proteins

Author

Sterzenbach, Ulrich and Sterzenbach, Ulrich

Abstract

A critical component for devising drug delivery systems is to package and protect molecules with the ability to release them specifically in a temporal and spatial manner. To date a number of systems have been developed as drug delivery vehicles; however, many have limitations in regard to immunogenicity, packaging efficiency and stability. Recent interest in vectors has shifted to naturally occurring nanovesicles called exosomes which can package proteins, lipids, DNA and various forms of RNA for delivery to recipient cells. These small vesicles are released from nearly every cell type and are known to play a role in cellular communication pathways through the delivery of the aforementioned cargo. However, mechanisms for loading functional molecules into exosomes are relatively unexplored. Here I report the use of the evolutionarily conserved late-domain (L-domain) pathway as a mechanism for loading exogenous proteins into exosomes. I demonstrate that labelling of a target protein, Cre recombinase, with a WW-tag leads to recognition by the L-domain protein Ndfip1, resulting in ubiquitination and loading into exosomes. My results show that Ndfip1 expression acts as a molecular switch for exosomal packaging of WW-Cre that can be suppressed using the exosome inhibitor GW4869. When taken up by floxed reporter cells, exosomes containing WW-Cre were capable of inducing DNA recombination indicating functional delivery of the protein to recipient cells. Using this functional in vitro assay I was able to identify differences in the communication potential between distinct cell types as well as the functionality of exosomes after storage. Engineered exosomes were administered to the brain of transgenic reporter mice using the nasal route to test for intracellular protein delivery in vivo. This resulted in the transport of engineered exosomes predominantly to recipient neurons in a number of brain regions. The ability to engineer exosomes to deliver biologically active protei

Published
2016

3. Positional differences of axon growth rates between sensory neurons encoded by Runx3

Author

Lallemend, Francois, Sterzenbach, Ulrich, Hadjab-Lallemend, Saida, Aquino, Jorge B, Castelo-Branco, Goncalo, Sinha, Indranil, Villaescusa, J Carlos, Levanon, Ditsa, Wang, Yiqiao, Franck, Marina C M, Kharchenko, Olga, Adameyko, Igor, Linnarsson, Sten, Groner, Yoram, Turner, Eric, and Ernfors, Patrik

Subjects
AXON GROWTH, Ciencias Biológicas, DEVELOPMENT, RUNX3, Biología del Desarrollo, INTRINSIC, CIENCIAS NATURALES Y EXACTAS
Abstract

The formation of functional connectivity in the nervous system is governed by axon guidance that instructs nerve growth and branching during development, implying a similarity between neuronal subtypes in terms of nerve extension. We demonstrate the molecular mechanism of another layer of complexity in vertebrates by defining a transcriptional program underlying growth differences between positionally different neurons. The rate of axon extension of the early subset of embryonic dorsal root ganglion sensory neurons is encoded in neurons at different axial levels. This code is determined by a segmental pattern of axial levels of Runx family transcription factor Runx3. Runx3 in turn determines transcription levels of genes encoding cytoskeletal proteins involved in axon extension, including Rock1 and Rock2 which have ongoing activities determining axon growth in early sensory neurons and blocking Rock activity reverses axon extension deficits of Runx3−/− neurons. Thus, Runx3 acts to regulate positional differences in axon extension properties apparently without affecting nerve guidance and branching, a principle that could be relevant to other parts of the nervous system. Fil: Lallemend, Francois. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia Fil: Sterzenbach, Ulrich. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia Fil: Hadjab Lallemend, Saida. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia Fil: Aquino, Jorge Benjamin. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Castelo Branco, Goncalo. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia Fil: Sinha, Indranil. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia Fil: Villaescusa, J. Carlos. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia Fil: Levanon, Ditsa. The Weizmann Institute of Science; Israel Fil: Wang, Yiqiao. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia Fil: Franck, Marina C. M.. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia Fil: Kharchenko, Olga. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia Fil: Adameyko, Igor. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia Fil: Linnarsson, Sten. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia Fil: Groner, Yoram. The Weizmann Institute of Science; Israel Fil: Turner, Eric. Seattle Children's Research Institute; Estados Unidos Fil: Ernfors, Patrik. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia

Published
2014
Full Text
View/download PDF

5. Positional differences of axon growth rates between sensory neurons encoded by runx3

Author

Lallemend, Francois, primary, Sterzenbach, Ulrich, additional, Hadjab-Lallemend, Saida, additional, Aquino, Jorge B, additional, Castelo-Branco, Goncalo, additional, Sinha, Indranil, additional, Villaescusa, J Carlos, additional, Levanon, Ditsa, additional, Wang, Yiqiao, additional, Franck, Marina C M, additional, Kharchenko, Olga, additional, Adameyko, Igor, additional, Linnarsson, Sten, additional, Groner, Yoram, additional, Turner, Eric, additional, and Ernfors, Patrik, additional

Published
2012
Full Text
View/download PDF

6. A Local Source of FGF Initiates Development of the Unmyelinated Lineage of Sensory Neurons.

Author

Hadjab, Saïda, Franck, Marina C. M., Yiqiao Wang, Sterzenbach, Ulrich, Sharma, Anil, Ernfors, Patrik, and Lallemend, Francois

Subjects
SENSORY neurons, NERVE growth factor receptors, PAIN perception, GENE expression, TRANSCRIPTION factors, PHENOTYPES
Abstract

The principle by which unmyelinated primary sensory neurons transducing thermal, itch and pain perception are specified in early development is unknown. These classes of sensory neurons diversify from a common population of late-born neurons, which initiate expression of Runt homology domain transcription factorRUNX1and the nerve growth factor receptor TrkA. Here, we report that signals emanating from within the mouse dorsal root ganglion mediated partly by early-born neurons destined to a myelinated phenotype participate in fating late-born RUNX1/TrkA neurons. Inductive factors include FGFs via activation of FGF receptor 1 (FGFR1). Consistently, FGF2 is sufficient to induce expression of RUNX1, and Fgfr1 conditional mutant mice display deficits in fating of the common population of late-born RUNX1/TrkA neurons that develop into unmyelinated neurons. Thus, the distinct lineages of sensory neurons are acquired in response to increasing FGF levels provided by a rising number of born neurons. [ABSTRACT FROM AUTHOR]

Published
2013
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results