Protein mass spectrometry toolkit for monitoring autophagy
The goal of this project is to develop a mass spectrometry (MS)-based read-out to evaluate autophagy progression. A major current limitation in assessing autophagy in animal models and monitoring the efficacy of autophagy-modulating therapies in patients is the absence of a small-scale quantitative and reliable assay. MS is a very sensitive technology that can be applied to obtain multiplexing targeted protein quantification. Upon autophagy induction, cellular levels of several ATG proteins increase while those of the autophagy receptors decrease because degraded together with the structures targeted to degradation. This project aims at developing quantitative MS assays to identify a set of biomarkers for prediction and monitoring of autophagy progression.
Increased autophagy levels are a common feature in the pathogenesis of liver disorders. The PhD student will monitor the levels of ATG proteins and autophagy receptors upon autophagy induction in various liver cell lines by MS, and determine which ones of these factors fluctuate the most. The most promising hits will be re-examined in the same cell lines after autophagy has been genetically and/or pharmacologically inhibited, to establish whether the changes are indeed caused by autophagy induction. The factors passing this selection will be then analysed in cells lines and organoids obtained from mouse livers, as well as in liver tissues obtained from mice models where autophagy has been induced/inhibited. This approach will allow charting the changes in cellular levels and establish which marker proteins can be used as a read-out to monitor progression of autophagy in liver. As a final proof-of-principle, these findings will be evaluated in biopsies from healthy individual and patients with liver diseases. The PhD student will also explore whether the same marker proteins could be used in other tissues taking advantage of models available within DRIVE.
Location: QPS, Groningen, The Netherlands/ the PhD student will be hosted in the Group of Prof. Dr. Fulvio Reggiori at the University Medical Center Groningen in the last year of her/his employment contract.
Supervisor: Dr. Fabrizia Fusetti
Length of appointment: 36 months (3 years) + 12 months (1 year)
Indicative Starting date: May 2018
Type of Contract: temporary
Hours per week: 36 hours
Deadline for application is 9 January 2018 at 23.59 h Brussels time zone gmt.
UPDATE: This vacancy is now closed.
More information about the host laboratory can be found at https://www.qps.com/