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ER-phagy mechanism and function in cancer

  • Full or part time
  • Application Deadline
    Thursday, February 20, 2020
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

About This PhD Project

Project Description

This PhD studentship funded by CRUK and is available to start in September 2020 at the Cancer Research UK Edinburgh Centre, which is part of the Institute of Genetics and Molecular Medicine (IGMM) at the University of Edinburgh. Applicants should hold at least an upper second-class degree in a relevant subject and comply with the University of Edinburgh’s English language requirements. Applicants should submit a covering letter and CV for consideration, along with details of 2 academic referees.

The overall goal of this studentship is to investigate ER-phagy mechanism and function in cancer.

Pancreatic cancer has a dismal 5-year survival rate of 5%. Reduced autophagy function promotes pancreatic cancer initiation whereas autophagy provides a potential therapeutic target in established disease. The mechanism(s) underpinning these roles for autophagy are currently poorly identified, precluding identification of viable molecular targets. Mechanistically, autophagy acts to degrade damaged organelles: endoplasmic reticulum (ER); mitochondria; lysosomes. Our latest data show that ER-phagy, in particular, has a principal role in pancreatic cancer. ER-phagy is only recently discovered and is incompletely characterised at the molecular level.

Aim 1 will be to employ proximity proteomic techniques to identify key molecules of the ER-phagy pathway in pancreatic cancer cells and to characterise these mechanistically, particularly in 3D organoid cultures. Aim 2 will test the function of two already identified molecule(s) in pancreatic cancer models in vivo. Overall, an understanding of ER-phagy and its therapeutic potential in pancreatic cancer will be acquired; a particular focus will be on understanding how ER-phagy affects ER protein homeostasis and, consequently, secreted signals regulating pancreatic cancer.

Wilkinson group website: https://www.ed.ac.uk/cancer-centre/research/wilkinson-group

References

Wilkinson, S. Emerging principles of selective ER autophagy. JMB. (2019). https://doi.org/10.1016/j.jmb.2019.05.012
Smith, M et al. CCPG1 Is a Non-canonical Autophagy Cargo Receptor Essential for ER-Phagy and Pancreatic ER Proteostasis. Developmental Cell. (2018). 44:217 doi:/10.1016/j.devcel.2017.11.024

Dikic, I and Elazar, Z. Mechanism and medical implications of mammalian autophagy. Nat Rev Mol Cell Biol (2018) 19(6):349-364
Gopinathan A et al. GEMMs as preclinical models for testing pancreatic cancer therapies. Dis Model Mech. 2015;8(10):1185–1200. doi:10.1242/dmm.021055

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