MRC Prion Unit and Institute of Prion diseases


Peter Klöhn

Cellular mechanisms of prion propagation

Peter Klöhn


Tel: 020 7679 5140
Courtauld Building, Room 101B

UCL Profile • PubMed


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). 

Selected Publications

Prion protein conversion at two distinct cellular sites precedes fibrillisation.
Ribes JM, Patel MP, Halim HA, Berretta A, Tooze SA, Klöhn PC.Nat Commun. 2023 Dec 15;14(1):8354. doi: 10.1038/s41467-023-43961-1.PMID: 38102121 Free PMC article.

Prion Propagation is Dependent on Key Amino Acids in Charge Cluster 2 within the Prion Protein.
Bhamra S, Arora P, Manka SW, Schmidt C, Brown C, Rayner MLD, Klöhn 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: 36535427

A New Cell Model for Investigating Prion Strain Selection and Adaptation.
Philiastides A Ribes JM Yip DC Schmidt C Benilova I Klöhn PC
Viruses. 2019 Sep 22;11(10). pii: E888. doi: 10.3390/v11100888.


Physical, chemical and kinetic factors affecting prion infectivity.
Properzi FBadhan AKlier SSchmidt CKlöhn PCWadsworth JDClarke ARJackson GSCollinge J.

Prion. 2016 May 3;10(3):251-61. doi: 10.1080/19336896.2016.1181250.

A systematic investigation of production of synthetic prions from recombinant prion protein.
Schmidt CFizet JProperzi FBatchelor MSandberg MKEdgeworth JAAfran LHo SBadhan AKlier SLinehan JMBrandner SHosszu LLTattum MHJat PClarke ARKlöhn PCWadsworth JDJackson GSCollinge J.
Open Biol. 2015 Dec;5(12):150165. doi: 10.1098/rsob.150165.

Identification of a gene regulatory network associated with prion replication.
Marbiah MMHarvey AWest BTLouzolo ABanerjee PAlden JGrigoriadis AHummerich HKan HMCai YBloom GSJat PCollinge JKlöhn PC.

EMBO J. 2014 Jul 17;33(14):1527-47. doi: 10.15252/embj.201387150. Epub 2014 May 19.

Plasmacytoid dendritic cells sequester high prion titres at early stages of prion infection.
Castro-Seoane RHummerich HSweeting TTattum MHLinehan JMFernandez de Marco MBrandner SCollinge JKlöhn PC.
PLoS Pathog. 2012 Feb;8(2):e1002538. doi: 10.1371/journal.ppat.1002538. Epub 2012 Feb 16.

PrP antibodies do not trigger mouse hippocampal neuron apoptosis.
Klöhn PCFarmer MLinehan JMO'Malley CFernandez de Marco MTaylor WFarrow MKhalili-Shirazi ABrandner SCollinge J.
Science. 2012 Jan 6;335(6064):52. doi: 10.1126/science.1215579.