High content biology
High-throughput screening using classical and chemical genetic approaches has emerged as a powerful tool to identify cellular pathways, potential therapeutic targets and therapeutic lead compounds. For a long time disregarded as “fishing expeditions”, it is now accepted that functional genomic screening is the way forward for making unexpected, ground-breaking discoveries in biomedical research.
In fact, much of what we know about how cells function has come from unbiased screening approaches. This paradigm shift has been facilitated by the availability of complete genome sequences and the advent of gene-specific knockdown technologies using RNA Interference (RNAi) and CRISPR/Cas9 genome editing.
The High Content Biology Laboratory uses high-throughput screening techniques to facilitate translational research. A main emphasis is the use of high-content screening techniques. In addition, our instrumentation allows analysis of various other assay systems including confocal microscopy, fluorescence, absorbance, luminescence and flow cytometry. We are using small molecule, cDNA, siRNA and CRISPR/Cas9 screening libraries.
We provide a high-throughput screening platform for projects that involve biosafety level 3 pathogens such as human Immunodeficiency Virus or Hepatitis Virus. This platform is located at our sister site at the Wohl Virion Centre, University College London, and uses a unique setup of liquid handling robots (CyBio WellVario, CyBi Drop) in a biosafety cabinet that enables fully automated processing of infectious samples in a 384-well format.
In addition, we work closely with the MRC Dementia Platform UK and have integrated specialized equipment for the use of induced pluripotent derived stem cells and primary neurons in high-content screening.
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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;8:294. 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.
The high-content biology platform is located in the UCL Medical Sciences/Anatomy building and invites projects from all faculties at UCL. If you are interested in screening, using equipment or just for advice and expertise, please contact Robin Ketteler.
Buzz Baum (LMCB, UK)
Daniel Cutler (LMCB, UK)
Rob De Bruin (LMCB, UK)
Paul Gissen (LMCB, UK)
Ricardo Henriques (LMCB, UK)
Janos Kriston-Vizi (LMCB, UK)
Alison Lloyd (LMCB, UK)
Mark Marsh (LMCB, UK)
Jason Mercer (LMCB, UK)
Sara Mole (LMCB, UK)
Franck Pichaud (LMCB, UK)
Chris Stefan (LMCB, UK)
Daniel Hochhauser (UCL Cancer Institute, UK)
Paolo Salomoni (UCL Cancer Institute, UK)
Tom Warner (UCL Institute of Neurology, UK)
Helene Plun-Favreau (UCL Institute of Neurology, UK)
Sarah Tabrizi (UCL Institute of Neurology, UK)
Aroon Hingorani (UCL Farr Institute, UK)
JP Romero (UCL Farr Institute, UK)
Paul Whiting (ARUK DDI, UK)
Ariberto Fassati (WIBR, UK)
Dagan Jenkins (UCL ICH, UK)
Francesco Muntoni (UCL ICH, UK)
Vania Braga (Imperial College London, UK)
Gabor Foldes (Imperial College London, UK)
Richard Angell (UCL School of Pharmacy, UK)
Alan Holmes (UCL School of Pharmacy, UK)
Miriam Dwek (University of Westminster, UK)
Derek Hausenloy (UCL Hatter Institute, UK)
Paola Vergani (UCL NPP, UK)
Gyuri Szabadkai (UCL CDB, UK)