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LMCB - MRC Laboratory for Molecular Cell Biology

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Robin Ketteler's picture
LMCB Group Leader, High-content Biology Leader
 
+44 (0)20 7679 4063
LMCB Room 2.03
 
Cell Signalling and Autophagy

Research Synopsis

In every cell, growth, proliferation and survival are key processes that require tight regulation by signal transduction pathways. Defects in this regulatory control can lead to severe diseases, such as cancer. Cells maintain a balance of growth and survival by two main processes: Growth factor signalling (under nutrient-rich conditions) and autophagy (under nutrient-scarce conditions). Over the past years, it has become clear that these processes are tightly co-regulated. In my lab we aim to elucidate the molecular interactions between these pathways. We use systematic genomic approaches to identify networks of cell signalling and autophagy. We employ high-throughput screening technologies as a means to identify novel components that modify cellular signal transduction pathways and autophagy. To this end, we are developing novel screening technologies based on arrayed CRISPR libraries and using knockout cell panels. Our studies will generate strategies for the identification of potential therapeutic targets in diseases such as cancer and neuro-degeneration. Further, we have the resources and expertise to translate these basic research findings into a drug discovery program to identify potential therapeutic lead compounds.

Selected Publications

Costa JR, et al (2017). Genome Editing Using Engineered Nucleases and Their Use in Genomic Screening. Assay Guidance Manual [Internet]. Bethesda (MD): Eli Lilly & Company and the National Center for Advancing Translational Sciences. PubMed PMID: 29165977.
Pengo N, et al (2017). A reversible phospho-switch mediated by ULK1 regulates the activity of autophagy protease ATG4B. Nat Commun. 8(1):294. doi:10.1038/s41467-017-00303-2
Ketteler R, et al (2017). Image-based siRNA screen to identify kinases regulating Weibel-Palade body size control using electroporation. Sci Data. 4:170022. doi:10.1038/sdata.2017.22. Erratum in: Sci Data. 4:170086. PubMed PMID:28248923
Petschnigg J, et al (2017). Systematic Identification of Oncogenic EGFR Interaction Partners. J Mol Biol. 429(2):280-294. doi: 10.1016/j.jmb.2016.12.006.
Costa JR, et al (2016). Autophagy gene expressionprofiling identifies a defective microtubule-associated protein light chain 3A mutant in cancer. Oncotarget. 7(27):41203-41216. doi:10.18632/oncotarget.9754. 
Prak K, et al (2016). Benzobisthiazoles Represent a Novel Scaffold for Kinase Inhibitors of CLK Family Members. Biochemistry. 55(3):608-17. doi:10.1021/acs.biochem.5b01128
Shanks E, et al (2015). Academic drug discovery within the United Kingdom: a reassessment. Nat Rev Drug Discov. 14(7):510. doi:10.1038/nrd4661

Funders

Medical Research Council
Action Medical Research

Research Themes

Signalling pathways, Electron Microscopy

Technology

Light microscopy, Electron microscopy, Translational research, Bioinformatics

People

Joana Costa (Postdoctoral Fellow)
Christin Luft (Postdoctoral Fellow)
Eliona Tsefou (Postdoctoral Fellow)
Tanya Singh (Research Associate)
Alexander Agrotis (PhD Student)
Apostolos Papandreou (PhD Student)
 

Collaborators

Paul Gissen (LMCB, UK)
Dan Cutler (LMCB, UK)
Mark Marsh (LMCB, UK)
Chris Stefan, (LMCB, UK)
Jason Mercer (LMCB, UK)
Ricardo Henriques (LMCB, UK)
Tom Warner (UCL, UK)
Manju Kuryian (UCL, UK)
Igor Stagljar (University of Toronto, Canada)