Protein localization and mitochondrial diseases

1 PhD project offered in the IPP winter call 2022/2023

Scientific Background

Correct localization of proteins throughout the different subcellular compartments is essential for cell functionality. Protein mislocalization is a constitutive problem caused by inherent inefficiencies of cellular processes and increases with aging. Proteins can also mislocalize due to mutations, as seen in various mitochondrial diseases. Mitochondrial diseases are the most common group of inherited metabolic disorders and are among the most common forms of inherited neurological disorders. Yet, the signals targeting proteins to mitochondria are not well understood. Thus, understanding how correct subcellular protein localization is achieved 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 the signals targeting proteins to mitochondria. We will take advantage of powerful yeast genetics and a new method for deep mutational scanning of localization signals developed in the group to define different mitochondrial targeting motifs and to understand the impact of disease mutations.
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 high-throughput fluorescence microscopy, deep sequencing techniques, biochemistry and molecular biology tools to uncover the features that are necessary to achieve protein localization to mitochondria. Excellent core facilities in the institute will provide the necessary support with fluorescence microscopy, sequencing and biochemistry requirements of the project.

Publications relevant to the project

Kong KYE*, Fischer B*, Meurer M*, Kats I, Li Z, Rühle F, Barry JD, Kirrmaier D, Chevyreva V, San Luis BJ, Costanzo M, Huber W, Andrews BJ, Boone C, Knop M# and Khmelinskii A# (2021) Timer-based proteomic profiling of the ubiquitin-proteasome system reveals a substrate receptor of the GID ubiquitin ligase Mol Cell, 81:2460-2476.e11

Meurer M*, Duan Y*, Sass E*, Kats I, Herbst K, Buchmuller BC, Dederer V, Huber F, Kirrmaier D, Stefl M, Van Laer K, Dick TP, Lemberg MK, Khmelinskii A#, Levy ED#, Knop M# (2018) Genome-wide C-SWAT library for high-throughput yeast genome tagging. Nature Methods 15:598-600

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


Dr. Anton Khmelinskii