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MRC Prion Unit and Institute of Prion diseases

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Peter Kl枚hn

Cellular mechanisms of prion propagation

Peter Kl枚hn

p.kloehn@prion.ucl.ac.uk

Tel: 020 7679 5140
Courtauld Building, Room 101B

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Research Synopsis

Prions, the infectious agents that cause the lethal brain disease Creutzfeldt-Jakob disease (CJD) in humans infect a range of different cells in the brain and in the periphery. In contrast to other infectious diseases, like viral or bacterial diseases, prions are not recognised as rogue proteins by the immune system and therefore expand rapidly and unhindered.

We seek to better understand how prions replicate in neuronal cells to identify novel ways for therapeutic intervention. Engineering of prion-susceptible cell models enables us to scrutinise the molecular underpinnings of protein misfolding. This helps us to identify gene regulatory networks that are associated with prion replication and secretion. Identification of antibodies that specifically recognise disease-associated forms of the prion protein in our laboratory will greatly support our endeavour to investigate prion replication in vivo and in vitro

PK Fig 1

To investigate what gene-encoded proteins contribute to prion propagation we establish cell models and diagnostic assays. The prion protein (PrP) can be visualised in healthy and prion-infected cells with antisera against PrP (panel A). While PrP decorates the membranes in control cells, aggregates of misfolded PrP are apparent in the periphery of infected cells. The Scrapie Cell Assay helps us to quantify the degree of prion infection (panel B).听

Selected Publications


Ribes JM, Patel MP, Halim HA, Berretta A, Tooze SA, Kl枚hn PC.Nat Commun. 2023 Dec 15;14(1):8354. doi: 10.1038/s41467-023-43961-1.PMID:听38102121听Free PMC article.


Bhamra S, Arora P, Manka SW, Schmidt C, Brown C, Rayner MLD, Kl枚hn PC, Clarke AR, Collinge J, Jat PS.J Mol Biol. 2023 Feb 28;435(4):167925. doi: 10.1016/j.jmb.2022.167925. Epub 2022 Dec 16.PMID:听36535427

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Philiastides A ,听Ribes JM ,听Yip DC ,听Schmidt C ,听Benilova I ,听Kl枚hn PC
听2019 Sep 22;11(10). pii: E888. doi: 10.3390/v11100888.
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Properzi F,听Badhan A,听Klier S,听Schmidt C,听Kl枚hn PC,听Wadsworth JD,听Clarke AR,听Jackson GS,听Collinge J.
Prion.听2016 May 3;10(3):251-61. doi: 10.1080/19336896.2016.1181250.


Schmidt C,听Fizet J,听Properzi F,听Batchelor M,听Sandberg MK,听Edgeworth JA,听Afran L,听Ho S,听Badhan A,听Klier S,听Linehan JM,听Brandner S,听Hosszu LL,听Tattum MH,听Jat P,听Clarke AR,听Kl枚hn PC,听Wadsworth JD,听Jackson GS,听Collinge J.
Open Biol.听2015 Dec;5(12):150165. doi: 10.1098/rsob.150165.


Marbiah MM,听Harvey A,听West BT,听Louzolo A,听Banerjee P,听Alden J,听Grigoriadis A,听Hummerich H,听Kan HM,听Cai Y,听Bloom GS,听Jat P,听Collinge J,听Kl枚hn PC.
EMBO J.听2014 Jul 17;33(14):1527-47. doi: 10.15252/embj.201387150. Epub 2014 May 19.


Castro-Seoane R,听Hummerich H,听Sweeting T,听Tattum MH,听Linehan JM,听Fernandez de Marco M,听Brandner S,听Collinge J,听Kl枚hn PC.
PLoS Pathog.听2012 Feb;8(2):e1002538. doi: 10.1371/journal.ppat.1002538. Epub 2012 Feb 16.


Kl枚hn PC,听Farmer M,听Linehan JM,听O'Malley C,听Fernandez de Marco M,听Taylor W,听Farrow M,听Khalili-Shirazi A,听Brandner S,听Collinge J.
Science.听2012 Jan 6;335(6064):52. doi: 10.1126/science.1215579.

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