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Dr Peter-Christian Kloehn
Address:Institute of Neurology MRC Prion Unit,
Appointments:Honorary Lecturer, Institute of Neurology, Faculty of Brain Sciences
We are focussing on two fundamental questions to better characterise the molecular underpinnings of prion pathogenesis. Firstly, we aim to identify genetic factors that facilitate or impede prion replication and pathogenesis and secondly, we seek to investigate the underlying molecular events for the dissemination of prions in the periphery.
To better understand how proteins misfold and cause disease in the host we study the transcriptomes of prion-susceptible and resistant cells. Candidate genes can then be overexpressed or silenced in vitro and in vivo to elucidate their role in prion replication and disease. We established recombinational cloning (Gateway cloning) to efficiently shuttle DNA fragments between different cloning vectors and use viral-mediated gene delivery to determine effects of gene perturbation in vitro and in vivo.
We recently showed evidence that cells of the innate immune system, like dendritic cells and natural killer cells sequester high amounts of prions. Intriguingly, prions were secreted from immune cells in form of infectious nanoparticles, so-called exosomes.
We offer internships for students, who are interested in learning and applying state-of-the-art methods in molecular biology.
- Cellular mechanisms underlying neurodegeneration
Displaying 6 most recent publications. For the full list please visit UCL Discovery
- Castro-Seoane R,Hummerich H,Sweeting T,Tattum MH,Linehan JM,Fernandez de Marco M,Brandner S,Collinge J,Klöhn PC (2012) Plasmacytoid dendritic cells sequester high prion titres at early stages of prion infection. PLoS Pathog, 8(2), e1002538. 10.1371/journal.ppat.1002538.
- Klöhn PC,Farmer M,Linehan JM,O'Malley C,Fernandez de Marco M,Taylor W,Farrow M,Khalili-Shirazi A,Brandner S,Collinge J (2012) PrP antibodies do not trigger mouse hippocampal neuron apoptosis. Science, 335(6064), 52. 10.1126/science.1215579.
- Julius C,Hutter G,Wagner U,Seeger H,Kana V,Kranich J,Klöhn PC,Weissmann C,Miele G,Aguzzi A (2008) Transcriptional stability of cultured cells upon prion infection. J Mol Biol, 375(5), 1222 - 1233. 10.1016/j.jmb.2007.11.003.
- Mahal SP,Demczyk CA,Smith EW,Klohn PC,Weissmann C (2008) Assaying prions in cell culture: the standard scrapie cell assay (SSCA) and the scrapie cell assay in end point format (SCEPA). Methods Mol Biol, 459, 49 - 68. 10.1007/978-1-59745-234-2_4.
- Heikenwalder M,Zeller N,Seeger H,Prinz M,Klöhn PC,Schwarz P,Ruddle NH,Weissmann C,Aguzzi A (2005) Chronic lymphocytic inflammation specifies the organ tropism of prions. Science, 307(5712), 1107 - 1110. 10.1126/science.1106460.
- Mallucci G,Dickinson A,Linehan J,Klohn PC,Brandner S,Collinge J (2003) Depleting neuronal PrP in prion infection prevents disease and reverses spongiosis Science, 302(5646), 871 - 874. 10.1126/science.1090187.
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