MRC Funded
Northwood
Project with
Autophagy is a lysosomal degradation pathway that is activated upon stress to facilitate clearance of damaged/toxic intracellular contents and recycle essential building blocks to sustain cell survival. The Liang Lab has a particular interest in understanding the physiological roles and pathological impacts of endoplasmic reticulum-specific autophagy (ER-phagy). We previously performed genome-wide CRISPR/Cas9 screens and uncovered many novel players that regulate ER-phagy (Liang and Corn, 2022). This includes a Ubiquitin-like modification, known as UFMylation, which we implicated in ER-phagy and ER stress regulation (Liang et al., 2020, Liang et al. 2018). Clinical mutation of genes involved in the UFMylation pathway results in striking neurodevelopmental, immunological and hematopoetic defects, underscoring the potential involvement of ER-phagy in these biologies.
A PhD project is available to understand the roles of other novel ER-phagy players uncovered from our genome-wide CRISPR screen. This project will utilise state-of-the-art microscopy, protein biochemistry, fluorescence microscopy, and CRISPR-based genetic manipulations to explore the roles of various novel factors in ER-phagy regulation and how their dysregulation translates to pathology.
Reference:
- Liang, JR and Corn, JE 2022. A CRISPR view on autophagy. Trends in Cell Biology.
- Liang JR, Lingeman E, Luong T, Ahmed S, Muhar M, Nguyen T, Olzmann JA, Corn JE (2019) A genome-wide screen for ER autophagy highlights key roles of mitochondrial metabolism and ER-resident UFMylation Cell 180 1160-1177
- Liang JR, Lingeman E, Ahmed S, Corn JE (2018) Atlastins remodel the endoplasmic reticulum for selective autophagy. Journal of Cell Biology J Cell Biol 217 3354-3367