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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

Frampton D, et al (2018). Molecular Signatures of Regression of the Canine Transmissible Venereal Tumor. Cancer Cell. Apr 9;33(4):620-633.e6. doi:10.1016/j.ccell.2018.03.003.
Pathania M, et al (2017). H3.3(K27M) Cooperates with Trp53 Loss and PDGFRA Gain in Mouse Embryonic Neural Progenitor Cells to Induce Invasive High-Grade Gliomas. Cancer Cell. Nov 13;32(5):684-700.e9. doi:10.1016/j.ccell.2017.09.014. 
Pengo N, et al (2017). A reversible phospho-switch mediated by ULK1 regulates the activity of autophagy protease ATG4B. Nat Comm. Aug 18;8(1):294. doi:10.1038/s41467-017-00303-2.
Petschnigg J, et al (2016). Systematic Identification of Oncogenic EGFR Interaction Partners. J Mol Biol. Jan 20;429(2):280-294. doi:10.1016/j.jmb.2016.12.006.
Yao Z, et al (2015). Application guide for omics approaches to cell signaling. Nat Chem Biol. Jun;11(6)387-97. doi:10.1038/nchembio.1809. 
Agrotis A & Ketteler R (2015). A new age in functional genomics using CRISPR/Cas9 in arrayed library screening. Front Genet. Sep 24;6:300. doi:10.3389/fgene.2015.00300.
Ferraro F, et al (2014). A two-tier Golgi-based control of organelle size underpins the functional plasticity of endothelial cells. Dev Cell. May 12;29(3):292-304. doi: 10.1016/j.devcel.2014.03.021.
 

Funders

Medical Research Council
Action Medical Research
BBSRC

Research Themes

Signalling pathways, Electron microscopy

Technology

Light microscopy, Electron microscopy, Translational research, Bioinformatics, High-throughput screening, High content screening, Genome editing, siRNA, Expression cloning

People

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

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)
Anisur Rahman (UCL, UK)
Natasa Przulj (UCL, UK)
Igor Stagljar (University of Toronto, Canada)