Amgen Scholars Program
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Stylianos Michalakis

Prof. Dr. Stylianos Michalakis

Professor of Ocular Gene Therapy

Affiliation

Munich University Hospital (LMU)

Contact

LMU Klinikum
Augenklinik
Mathildenstr. 8
D-80336 München

Phone: +49 (0)89 - 2180 -77325
Fax: +49 (0)89 - 2180 -77326

Website: http://www.cipsm.de
Website: http://www.klinikum.uni-muenchen.de/Augenklinik-und-Poliklinik/de/forschung/gentherapie/english_version/index.html

Research Focus

Project description:

Microglia are the main resident immune cells of the nervous system and as such they are involved in multiple roles ranging from tissue homeostasis to response to insults and circuit refinement. This holds true for the retina, a thin layer lining the inner part of the eye where a fine network of different neuronal cells performs the first extensive processing. Similarly to many other nervous and non-nervous organs, the retina is affected by a plethora of degenerative pathologies, whose aetiology is not always fully understood. Accumulating evidence indicates retinal microglia that harbor a high degree of transcriptional, morphological and functional differences depending on state of activation and the environment, contribute to the pathobiology of retinal diseases. Thus, studying the roles and signatures adopted specifically by microglia in the retina has become increasingly important.

We have previously established a novel primary microglia culture protocol from mouse retina, which allows for good reproducibility, high cell numbers and long in vitro viability. In order to be able to efficiently manipulate retinal microglia in vivo and in vitro, efficient gene delivery technologies are needed. Within this project, we will evaluate novel-engineered adeno-associated virus (AAV) capsids regarding efficacy and specificity. These AAV variants will be tested in our mouse retinal microglia culture model, mouse retinal explant cultures and in a mouse model of retinal degeneration to validate their efficacy and specificity in vitro, ex vivo and in vivo.

Aim and methods:

The Amgen scholar will be introduced to this specific field, where he/she will learn the basics of retina physiology and pathology. The scholar will be in charge of establishing and maintaining primary retinal microglia cultures and mouse retinal explant cultures. Additionally, he/she will also contribute to the production and testing of AAV vectors used within this project. Finally, the candidate will be involved in histological processing (cryosectioning and immunolabeling) of mouse eye samples and the subsequent imaging using confocal microscopy.

Thus, the candidate will be offered the chance to learn a whole experimental pipeline - from establishing in vitro and ex vivo models to testing novel AAV vectors.