Protein quality control and ageing

1 PhD project offered in the IPP summer call 2021

Scientific background 

Protein quality control systems maintain a functional proteome through detection and removal of abnormal proteins. Among quality control substrates are mislocalized proteins, i.e., proteins that fail to reach their native compartment or fail to assemble into complexes, and thus cannot function normally. Protein mislocalization is a constitutive problem caused by inherent inefficiencies of cellular processes and increases with ageing. Proteins can also mislocalize due to mutations, as seen in various metabolic, cardiovascular and neurodegenerative diseases, and some types of cancer. Thus, understanding how cells deal with mislocalized proteins is not only important from the point of view of basic research but will also contribute to elucidating causes of diseases at the molecular level.

PhD project: Quality control of mislocalized proteins

In this project we will dissect quality control mechanisms of mislocalized proteins through a combination of high-throughput screening, molecular biology, genetics and biochemistry. We will take advantage of powerful yeast genetics and conditional protein mislocalization to screen for machinery involved in quality control of different types of mislocalized proteins, to understand how cells recognize mislocalized proteins as abnormal and to investigate the roles of such quality control systems in the ageing process.

We are looking for a highly motivated individual with a degree in Molecular Biology, Biochemistry, Biotechnology or related fields. The successful candidate will join an enthusiastic team and combine genetic screening approaches with proteomics, biochemistry and molecular biology techniques to uncover general principles of protein quality control. Excellent core facilities in the institute will provide the necessary support with mass spectrometry, sequencing and flow cytometry requirements of the project.

Publications relevant to the project

Dederer V, Khmelinskii A, Huhn AG, Okreglak V, Knop M and Lemberg MK (2019) Cooperation of mitochondrial and ER factors in quality control of tail-anchored proteinseLife, 8:e45506 Link

Meurer M, Duan Y, Sass E, Kats I, Herbst K, Buchmuller BC, Dederer V, Huber F, Kirrmaier D, Štefl M, Van Laer K, Dick TP, Lemberg MK, Khmelinskii A#, Levy ED# and Knop M# (2018) Genome-wide C-SWAT library for high-throughput yeast genome taggingNat Methods, 15:598–600 (#indicates joint correspondence) Link

Kats I, Khmelinskii A, Kschonsak M, Huber F, Knieß RA, Bartosik A and Knop M (2018) Mapping degradation signals and pathways in a eukaryotic N-terminomeMol Cell, 70:488–501.e5 Link

Khmelinskii A*, Blaszczak E*, Pantazopoulou M, Fischer B, Omnus DJ, Le Dez G, Brossard A, Gunnarsson A, Barry JD, Meurer M, Kirrmaier D, Boone C, Huber W, Rabut G, Ljungdahl PO and Knop M (2014) Protein quality control at the inner nuclear membraneNature, 516:410–413 (*indicates joint contribution) Link



Dr Anton Khmelinskii