Georg Kustatscher

Systems biology of proteome dynamics.

Georg studied Molecular Biology at the University of Salzburg, Austria, and obtained a PhD from the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, working on epigenetics in the lab of Andreas Ladurner. From 2008 to 2020 he was a Postdoc in Juri Rappsilber’s proteomics group at the Wellcome Centre for Cell Biology in Edinburgh. 

In 2020 he established a research group at the University of Edinburgh, supported by an MRC Career Development Award. 

portrait photo of Georg Kustatscher
Georg Kustatscher

The lab has two key aims: (a) to identify biological functions of understudied proteins in a large-scale, data-driven manner, and (b) to understand, from a systems biology perspective, how cells regulate protein levels via translation and protein degradation. The group addresses these questions using both wet-lab proteomics and computational approaches, including machine learning.

Savvas Kourtis, Shreyas Niphadkar, Jonathan Meyrick, Ayush Regmi Bagale, Louise Chapman, and Amber Minhas


Protein levels in cells are controlled through a complex interplay of synthesis and degradation, yet the principles governing this regulation remain poorly understood. Our lab investigates proteome dynamics from two complementary perspectives: understanding the mechanisms that control protein abundance, and using abundance patterns to predict protein function.

Understanding protein level regulation

There is a major discordance between mRNA and protein expression levels in human cells. Why is this so and what mechanisms are behind it? For example, aneuploidy - the aberrant gain or loss of individual chromosomes - is a hallmark of infertility, ageing and cancer. Despite increased gene copy numbers, proteins encoded on extra chromosomes often do not increase proportionally. Instead, cells buffer protein levels through regulatory mechanisms at the level of translation and protein degradation. We aim to understand how these processes maintain proteostasis and how they fail in disease.

Predicting protein function from abundance dynamics

Proteome dynamics also serves as a powerful tool for functional discovery. When cells are perturbed, proteins with similar functions tend to change in coordinated ways. By analysing these coordinated abundance changes across thousands of conditions, we can link understudied proteins to known functional modules and predict their biological roles. We are creating proteome covariation maps for multiple species, from yeast to human.


Diagram outlining the development of DIA-pulse-SILAC

Figure legend

Development of DIA-pulse-SILAC for the rapid and precise measurement of protein synthesis and degradation.

(A) Schematic of a pulse-SILAC experiment.

(B) SILAC titration series created by mixing defined ratios of light and heavy extracts from RPE1 cells. In a direct comparison our new DIA-SILAC workflow (DIA; data-independent acquisition) quantifies considerably more proteins than the traditional data-dependent acquisition (DDA) of SILAC samples.

(C) DIA-pulse-SILAC was used to quantify synthesis and degradation rates in RPE-1 cells. Two example proteins are shown.

Munro V, Kelly V, Messner CB, Kustatscher G. Cellular control of protein levels: A systems biology perspective (2024). Proteomics 24(12-13):e2200220. doi: 10.1002/pmic.202200220. 

Messner CB, Demichev V, Muenzner J, Aulakh SK, Barthel N, Röhl A, Herrera-Domínguez L, Egger AS, Kamrad S, Hou J, Tan G, Lemke O, Calvani E, Szyrwiel L, Mülleder M, Lilley KS, Boone C, Kustatscher G, Ralser M (2023). The proteomic landscape of genome-wide genetic perturbations. Cell Apr 27;186(9):2018-2034.e21. doi: 10.1016/j.cell.2023.03.026. 

Kustatscher G, Collins T, Gingras AC, Guo T, Hermjakob H, Ideker T, Lilley KS, Lundberg E, Marcotte EM, Ralser M, Rappsilber J (2022). Understudied proteins: opportunities and challenges for functional proteomics. Nat Methods Jul;19(7):774-779. doi: 10.1038/s41592-022-01454-x.


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