Understanding the molecular basis of cellular self-eating (autophagy)

Key information

Application close date
07 February 2023, 11:59 GMT
Hours per week
36 (full time)
Application guidance
Posted 22 December 2022

Research topics

Biochemistry & Proteomics Cell Biology Structural Biology & Biophysics
Background texture taken from the lab imagery.

This is a summer student position supervised by Carmen Oeo-Santos from Anne Schreiber's lab.

Introduction to the Science

Cells employ different mechanisms to degrade their cellular constituents. Autophagy mediates the degradation of a wide range of cytoplasmic material via the de novo formation of double-membrane vesicles (autophagosomes) that transport cytoplasmic material to the lysosome/vacuole for degradation, and the recycling of cellular building blocks within them.

While bulk autophagy randomly engulfs cytoplasmic material to maintain cellular homeostasis, selective autophagy pathways specifically take up a diverse range of cargos including damaged organelles (e.g. mitochondria or peroxisomes), protein aggregates, or invading intracellular pathogens (e.g. bacteria), thereby protecting cells from potentially harmful cytoplasmic structures. Hence, defects in these pathways have been associated with many human pathologies such as neurodegeneration, cancer or infectious diseases, emphazising the importance of understanding autophagy in more mechanistic and molecular detail, to inform the development of novel therapeutics to modulate these pathways.

About the Project

Autophagosome formation is a highly complex process requiring a multitude of proteins commonly known as autophagy-related (Atg) proteins. To overcome some of the technical limitations of studying the molecular mechanism of autophagosome formation in vivo, our lab has established an in vitro reconstitution approach to study the complex interplay and regulation of the core autophagy machinery in the test tube in unprecedented mechanistic detail. We are currently applying this approach to study how the autophagy machinery drives autophagosomal membrane formation and selective cargo uptake, and how posttranslational modifications regulate this process, validating all our findings by cell-based approaches.

In addition to our in vitro reconstitution experiments, the successful candidate will also learn a variety of approaches to monitor bulk and selective autophagy in vivo. Those studies may further be complemented by fluorescence or cryo-electron microscopy experiments.

About You

We are looking for highly motivated students eager to learn and enjoy the process of scientific discovery.

 

References

1.         Schreiber, A., Collins, B.C., Davis, C., Enchev, R.I., Sedra, A., D'Antuono, R., . . . Peter, M. (2021)

            Multilayered regulation of autophagy by the Atg1 kinase orchestrates spatial and temporal control of autophagosome formation.

            Molecular Cell 81: 5066-5081 e5010. PubMed abstract

2.         Hurley, J.H. and Young, L.N. (2017)

            Mechanisms of autophagy initiation.

            Annual Review of Biochemistry 86: 225-244. PubMed abstract