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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. 
 
 

Selected publications

Agrotis A, et al (2019). Human ATG4 autophagy proteases counteract attachment of ubiquitin-like LC3/GABARAP proteins to other cellular proteins. J Biol Chem. 2019 Jul 17. pii: jbc.AC119.009977. doi:10.1074/jbc.AC119.009977. [Epub ahead of print] PubMed PMID: 31315929.
Zhang C, et al (2019). Signalling involving MET and FAK supports cell division independent of the activity of the cell cycle-regulating CDK4/6 kinases. Oncogene. 2019 Jul 12. doi:10.1038/s41388-019-0850-2. [Epub ahead of print] PubMed PMID: 31296956.
Little D, et al (2019). Using stem cell-derived neurons in drug screening for neurological diseases. Neurobiol Aging. 2019 Jun;78:130-141.doi: 10.1016/j.neurobiolaging.2019.02.008. Epub 2019 Feb 20. Review. PubMed PMID:30925301.
Mazzon M, et al (2019). Identification of Broad-Spectrum Antiviral Compounds by Targeting Viral Entry. Viruses. 2019 Feb 20;11(2). pii:E176. doi: 10.3390/v11020176. PubMed PMID: 30791609; PubMed Central PMCID: PMC6410080.
Malod-Dognin N, et al (2019). Towards a data-integrated cell. Nat Commun. 2019 Feb 18;10(1):805. doi:10.1038/s41467-019-08797-8. Erratum in: Nat Commun. 2019 May 21;10(1):2324. PubMed PMID: 30778056; PubMed Central PMCID: PMC6379402.
 

About the facility

People

Robin Ketteler (Technology leader)
Christin Luft (Postdoctoral Fellow)
Denise Pilger (Postdoctoral Fellow) 
Nivedita Singh (Postdoctoral Fellow)

Research themes

High-throughput screening, High-content screening, siRNA screening, Drug discovery, CRISPR/Cas9 genome editing

Resources

Complete list of publications
Europe PMC | PubMed

User policies

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.  

Collaborations

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)
Manju Kurian (UCL ICH, UK)
Anisur Rahman (UCL Medicine)
Vania Braga (Imperial College London, UK)
Gabor Foldes (Imperial College London, UK)
Richard Angell (UCL School of Pharmacy, UK)
Gyuri Szabadkai (UCL CDB, UK)