m.sandberg@prion.ucl.ac.uk |
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Research Synopsis
Recent advances suggest that prions themselves are not directly neurotoxic, but rather their propagation involves production of toxic species which may be uncoupled from infectivity. A general model has been proposed to encompass these phenomena, centring on the kinetics of prion propagation.
Our research aims to characterise the kinetics of prion propagation and understand its relationship to prion strains, transmission barriers, the onset of neurological disease and clinically silent carrier states.
Selected Publications
Highly infectious prions are not directly neurotoxic.
Benilova I, Reilly M, Terry C, Wenborn A, Schmidt C, Marinho AT, Risse E, Al-Doujaily H, Wiggins De Oliveira M, Sandberg MK, Wadsworth JDF, Jat PS, Collinge J.Proc Natl Acad Sci U S A. 2020 Sep 22;117(38):23815-23822. doi: 10.1073/pnas.2007406117. Epub 2020 Sep 8.PMID: 32900920
A systematic investigation of production of synthetic prions from recombinant prion protein.
Schmidt C, Fizet J, Properzi F, Batchelor M, Sandberg MK, Edgeworth JA, Afran L, Ho S, Badhan A, Klier S, Linehan JM, Brandner S, Hosszu LL, Tattum MH, Jat P, Clarke AR, Klöhn PC, Wadsworth JD, Jackson GS, Collinge J.Open Biol. 2015 Dec;5(12):150165. doi: 10.1098/rsob.150165.PMID: 26631378
Prion neuropathology follows the accumulation of alternate prion protein isoforms after infective titre has peaked.
Sandberg MK, Al-Doujaily H, Sharps B, De Oliveira MW, Schmidt C, Richard-Londt A, Lyall S, Linehan JM, Brandner S, Wadsworth JD, Clarke AR, Collinge J.Nat Commun. 2014 Jul 9;5:4347. doi: 10.1038/ncomms5347.PMID: 25005024
N-terminal domain of prion protein directs its oligomeric association.
Trevitt CR, Hosszu LL, Batchelor M, Panico S, Terry C, Nicoll AJ, Risse E, Taylor WA, Sandberg MK, Al-Doujaily H, Linehan JM, Saibil HR, Scott DJ, Collinge J, Waltho JP, Clarke AR.J Biol Chem. 2014 Sep 12;289(37):25497-508. doi: 10.1074/jbc.M114.566588. Epub 2014 Jul 29.PMID: 25074940
A novel prion disease associated with diarrhea and autonomic neuropathy.
Mead S, Gandhi S, Beck J, Caine D, Gallujipali D, Carswell C, Hyare H, Joiner S, Ayling H, Lashley T, Linehan JM, Al-Doujaily H, Sharps B, Revesz T, Sandberg MK, Reilly MM, Koltzenburg M, Forbes A, Rudge P, Brandner S, Warren JD, Wadsworth JDF, Wood NW, Holton JL, Collinge J.N Engl J Med. 2013 Nov 14;369(20):1904-14. doi: 10.1056/NEJMoa1214747.PMID: 24224623
Prion propagation and toxicity in vivo occur in two distinct mechanistic phases.
Sandberg MK, Al-Doujaily H, Sharps B, Clarke AR, Collinge J.Nature. 2011 Feb 24;470(7335):540-2. doi: 10.1038/nature09768.PMID: 21350487
Chronic wasting disease prions are not transmissible to transgenic mice overexpressing human prion protein.
Sandberg MK, Al-Doujaily H, Sigurdson CJ, Glatzel M, O'Malley C, Powell C, Asante EA, Linehan JM, Brandner S, Wadsworth JD, Collinge J.J Gen Virol. 2010 Oct;91(Pt 10):2651-7. doi: 10.1099/vir.0.024380-0. Epub 2010 Jul 7.PMID: 20610667