ZMBH Open PhD positions

Open PhD positions

Selective Autophagy of the Endoplasmic Reticulum

The aim of this project is a molecular understanding of ER-phagy, a novel type of autophagy that selectively targets the Endoplasmic Reticulum (ER).

Cells use autophagy (literally: self-eating) for many purposes, including the degradation of random cytoplasm to generate nutrients during starvation and the disposal of toxic protein aggregates. Importantly, autophagy can selectively target damaged or redundant organelles. A poorly understood type of autophagy is the selective autophagy of ER. In yeast, protein folding problems in the ER trigger massive ER membrane expansion. In addition, they induce the formation of ER whorls, which are subsequently destroyed through autophagy. In this way, cells may sacrifice part of their ER to discard misfolded ER proteins, thereby making sure that the organelle works properly even under stressful conditions. In addition, cells may use ER-phagy to regulate ER size. ER-phagy does not require known autophagy genes and thus involves novel molecular machinery that remains to be identified.

In this ongoing project, we want to identify the genes involved in ER-phagy and elucidate how they bring about destruction of selected parts of the ER. We are currently conducting genetic screens in yeast to uncover the molecular machinery for ER-phagy and will use the biochemical and cell biological tools available in yeast to understand how this machinery works. At a later stage, we will apply the information gleaned from yeast to define ER-phagy in mammalian cells. We anticipate that ER-phagy has important physiological roles in maintaining ER homeostasis and is relevant for diseases that impinge on ER function, such as cancer and diabetes.

To find out more, please visit http://www.zmbh.uni-heidelberg.de/Schuck .

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