Ruprecht-Karls-Universit├Ąt Heidelberg
HBIGS homepage | Forgot password
Wittbrodt0117 - Scientist (f/m) / PhD position
Project no:

Project leader:

Project supervisor:
Wittbrodt, Jochen
Application deadline:
14. Feb 2018
Start of PhD project:
1. Mar 2018

Project description:

The role of ER-resident glycosylation in vertebrate neural development
The perception of the extracellular environment is of key importance in particular for neural development. Crucial events in neural development e.g. the neural plate patterning, neuroblast differentiation and migration, or axonal outgrowth highly depend on cell-surface interactions to facilitate cell-cell contacts, the adhesion to the cellular matrix or perception of extracellular signals. Extracellular surface proteins are modified by N-glycosylation (N-Glyco) as well as C- and O-mannosylation (O-Man) or combinations of these. These modifications affect protein functionality. Consequently, impaired glycosylation results in to severe defects of brain / neuronal development in human patients / animal models.
Fish models (medaka, Oryzias latipes) offer alternative routes to study glycosylation during neural development. Extrauterine development on the one hand allows the observation of phenotypes from the earliest stages onwards. Mutant cells can also be studied in the context of an otherwise wild type embryo (focusing on the stem cell niche of the eye) by clonal analysis following blastomere transplantation. This allows to overcome early embryonic lethality to study subsequent processes in neural development and growth. This fact, together with modern tools of genome editing (CRISPR/Cas9) facilitate the establishment and detailed molecular and developmental analyses of tractable animal models that closely resemble human syndromes.
Centanin L., et al. (2011) Fate restriction and multipotency in retinal stem cells. doi: 10.1016/j.stem.2011.11.004

Stemmer, Thumberger, et al. (2015) CCTop: An Intuitive, Flexible and Reliable CRISPR/Cas9 Target Prediction Tool. doi: 10.1371/journal.pone.0124633

Hennet and Cabalzar (2015) Congenital disorders of glycosylation: a concise chart of glycocalyx dysfunction. doi: 10.1016/j.tibs.2015.03.002
Methods that will be used:
advanced genetics, CRISPR/Cas9, experimental embryology, immunohistochemistry, molecular and cellular biology, advanced imaging
Cooperation partners:
Prof. Dr. Sabine Strahl (COS Heidelberg), PD Dr. Christian Thiel (Heidelberg University Hospital), Dr. Erdmann Rapp (MPI Magdeburg)
Personal qualifications:
Molecular and developmental biology, fluent in English, team player, enthusiasm, dedication for basic science
CRISPR/Cas, targeted gene interference, glycosylation, retinal stem cells, fish disease models