Georg Kustatscher

Georg Kustatscher
The University of Edinburgh | UoE · School of Biological Sciences

PhD

About

48
Publications
3,890
Reads
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1,965
Citations
Citations since 2016
25 Research Items
1109 Citations
2016201720182019202020212022050100150200
2016201720182019202020212022050100150200
2016201720182019202020212022050100150200
2016201720182019202020212022050100150200
Introduction
I'm a group leader at the Institute of Quantitative Biology (IQB3) in Edinburgh. The aim of my lab is to understand how cells regulate protein levels, and how these processes are disrupted in cancer cells. We address this question by combining proteomics, transcriptomics and computational approaches, including machine-learning.
Additional affiliations
September 2020 - present
The University of Edinburgh
Position
  • Group Leader
October 2008 - August 2020
The University of Edinburgh
Position
  • PostDoc Position
October 2004 - February 2008
European Molecular Biology Laboratory
Position
  • PhD Student

Publications

Publications (48)
Article
There are multiple reasons why the next generation of biological and medical studies require increasing numbers of samples. First, many conditions need to be considered to produce generalisable results. For example, biological systems are dynamic, and the effect of a perturbation depends on the genetic background and environment. Moreover, human po...
Article
Full-text available
Most research aiming at understanding the molecular foundations of life and disease has focused on a limited set of increasingly well-known proteins while the biological functions of many others remain poorly understood. We propose to form the Understudied Protein Initiative with the objective of reducing the annotation gap by systematically associ...
Article
Full-text available
We have used a combination of chemical genetics, chromatin proteomics, and imaging to map the earliest chromatin transactions during vertebrate cell entry into mitosis. Chicken DT40 CDK1as cells undergo synchronous mitotic entry within 15 min following release from a 1NM-PP1-induced arrest in late G2. In addition to changes in chromatin association...
Article
Full-text available
Comprehensive proteome analysis of rare cell phenotypes remains a significant challenge. We report a method for low cell number mass spectrometry (MS)-based proteomics using protease digestion of mildly formaldehyde-fixed cells in cellulo, which we call the ‘in-cell digest’. We combined this with AMPL (Averaged MS1 Precursor Library Matching) to qu...
Preprint
Full-text available
We have used a combination of chemical genetics, chromatin proteomics and imaging to map the earliest chromatin transactions during vertebrate cell entry into mitosis. Chicken DT40 CDK1as cells undergo synchronous mitotic entry within 15 minutes following release from a 1NM-PP1-induced arrest in late G2. In addition to changes in chromatin associat...
Article
Full-text available
Graphical Abstract Highlights d Comprehensive proteomics of replication forks damaged by TOP1 inhibition d Broken and stalled forks show distinct repairomes and chromatin environments d Rewiring of the broken fork proteome by ATM inhibition toward DSB ubiquitination d PLK1, NDRG3, and UBAP2 are promoting repair of broken forks by HR Correspondence...
Article
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Assigning functions to the vast array of proteins present in eukaryotic cells remains challenging. To identify relationships between proteins, and thereby enable functional annotation of proteins, we determined changes in abundance of 10,323 human proteins in response to 294 biological perturbations using isotope-labeling mass spectrometry. We appl...
Preprint
Full-text available
The annotation of protein function is a longstanding challenge of cell biology that suffers from the sheer magnitude of the task. Here we present ProteomeHD, which documents the response of 10,323 human proteins to 294 biological perturbations, measured by isotope-labelling mass spectrometry. Using this data matrix and robust machine learning we cr...
Preprint
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Gene co-expression analysis is a widespread method to identify the potential biological function of uncharacterised genes. Recent evidence suggests that proteome profiling may provide more accurate results than transcriptome profiling. However, it is unclear which statistical measure is best suited to detect proteins that are co-regulated. We have...
Article
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Genes are often co-expressed with their genomic neighbors, even if these are functionally unrelated. For small expression changes driven by genetic variation within the same cell type, non-functional mRNA co-expression is not propagated to the protein level. However, it is unclear if protein levels are also buffered against any non-functional mRNA...
Article
Full-text available
Genes are not randomly distributed in the genome. In humans, 10% of protein-coding genes are transcribed from bidirectional promoters and many more are organised in larger clusters. Intriguingly, neighbouring genes are frequently coexpressed but rarely functionally related. Here we show that coexpression of bidirectional gene pairs, and closeby gen...
Article
Full-text available
Ever-increasing numbers of quantitative proteomics datasets constitute a currently underexploited resource for investigating protein function. Multi-protein complexes often follow consistent trends in these experiments, which could provide insights about their biology. Yet, as more experiments are considered, a complex's signature may become condit...
Article
Full-text available
Proteomic studies find many proteins in unexpected cellular locations. Can functional components of organelles be distinguished from biochemical artefacts or misguided cellular sorting? The clue might reside in compositional changes that follow biological challenges and that can be decoded by machine learning.
Preprint
Full-text available
The large and ever-increasing numbers of quantitative proteomics datasets constitute a currently underexploited resource for drawing biological insights on proteins and their functions. Multiple observations by different laboratories indicate that protein complexes often follow consistent trends. However, proteomic data is often noisy and incomplet...
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Full-text available
Subcellular localisation is an important aspect of protein function, but the protein composition of many intracellular compartments is poorly characterised. For example, many nuclear bodies are challenging to isolate biochemically and thus remain inaccessible to proteomics. Here we explore covariation in proteomics data as an alternative route to s...
Article
During interphase, chromatin hosts fundamental cellular processes, such as gene expression, DNA replication and DNA damage repair. To analyze chromatin on a proteomic scale, we have developed chromatin enrichment for proteomics (ChEP), which is a simple biochemical procedure that enriches interphase chromatin in all its complexity. It enables resea...
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Full-text available
Chromatin proteins mediate replication, regulate expression, and ensure integrity of the genome. So far, a comprehensive inventory of interphase chromatin has not been determined. This is largely due to its heterogeneous and dynamic composition, which makes conclusive biochemical purification difficult, if not impossible. As a fuzzy organelle, it d...
Article
To maintain genome function and stability, DNA sequence and its organization into chromatin must be duplicated during cell division. Understanding how entire chromosomes are copied remains a major challenge. Here, we use nascent chromatin capture (NCC) to profile chromatin proteome dynamics during replication in human cells. NCC relies on biotin-dU...
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Full-text available
Lung cancer is the leading cause of cancer deaths. Despite optimal diagnosis and early treatment, many patients die of recurrent disease. There are no sufficiently useful biomarkers to predict the risk of tumor recurrence. Here, we show that expression of histone macroH2A1.1 and macroH2A2 predicts lung cancer recurrence, identifying these histone v...
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Full-text available
Poly-ADP-ribosylation is a post-translational modification catalyzed by PARP enzymes with roles in transcription and chromatin biology. Here we show that distinct macrodomains, including those of histone macroH2A1.1, are recruited to sites of PARP1 activation induced by laser-generated DNA damage. Chemical PARP1 inhibitors, PARP1 knockdown and muta...
Article
Specific cell activity results from developmental and environmental control over the expression of our genes. A key component in epigenetic forms of biological regulation is the methylation of lysine residues in histone proteins. This post-translational modification of chromatin has been vigorously studied over the past few years. Highly specific e...
Article
Histone macroH2A is a hallmark of mammalian heterochromatin. Here we show that human macroH2A1.1 binds the SirT1-metabolite O-acetyl-ADP-ribose (OAADPR) through its macro domain. The 1.6-A crystal structure and mutants reveal how the metabolite is recognized. Mutually exclusive exon use in the gene H2AFY produces macroH2A1.2, whose tissue distribut...
Article
Full-text available
The ADP-ribosylation of proteins is an important post-translational modification that occurs in a variety of biological processes, including DNA repair, transcription, chromatin biology and long-term memory formation. Yet no protein modules are known that specifically recognize the ADP-ribose nucleotide. We provide biochemical and structural eviden...

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