Protein biochemistry for development of novel medical treatments - Janne Johansson

Early work on SP-C lead to the discovery of a molecular chaperone domain (BRICHOS) that is the first described example of an endogenous defence against amyloid formation and toxicity. We have described physiological roles for BRICHOS and how dysfunction as a consequence of mutations can give rise to human disease. Based on these insights we are developing BRICHOS based biologic drugs against Alzheimer’s disease, which we are currently testing in mouse models with promising results.

We are also studying structural and functional properties of spider silk proteins and their constituent domains, with the ambition to understand how spider silk formation occurs in nature. By doing this we hope to be able to develop biomimetic artificial spider silk materials and biotechnological tools.

Group members

Selected publications

Augmentation of Bri2 molecular chaperone activity against amyloid-β reduces neurotoxicity in mouse hippocampus in vitro.
Chen G, Andrade-Talavera Y, Tambaro S, Leppert A, Nilsson HE, Zhong X, et al
Commun Biol 2020 01;3(1):32

Synthetic surfactants with SP-B and SP-C analogues to enable worldwide treatment of neonatal respiratory distress syndrome and other lung diseases.
Johansson J, Curstedt T
J. Intern. Med. 2019 02;285(2):165-186

Blood-brain and blood-cerebrospinal fluid passage of BRICHOS domains from two molecular chaperones in mice.
Tambaro S, Galan-Acosta L, Leppert A, Chen G, Biverstål H, Presto J, et al
J. Biol. Chem. 2019 02;294(8):2606-2615

BRICHOS domain of Bri2 inhibits islet amyloid polypeptide (IAPP) fibril formation and toxicity in human beta cells.
Oskarsson ME, Hermansson E, Wang Y, Welsh N, Presto J, Johansson J, et al
Proc. Natl. Acad. Sci. U.S.A. 2018 03;115(12):E2752-E2761

Bri2 BRICHOS client specificity and chaperone activity are governed by assembly state.
Chen G, Abelein A, Nilsson HE, Leppert A, Andrade-Talavera Y, Tambaro S, et al
Nat Commun 2017 12;8(1):2081

Efficient protein production inspired by how spiders make silk.
Kronqvist N, Sarr M, Lindqvist A, Nordling K, Otikovs M, Venturi L, et al
Nat Commun 2017 05;8():15504

A molecular chaperone breaks the catalytic cycle that generates toxic Aβ oligomers.
Cohen SIA, Arosio P, Presto J, Kurudenkandy FR, Biverstal H, Dolfe L, et al
Nat. Struct. Mol. Biol. 2015 Mar;22(3):207-213

Sequential pH-driven dimerization and stabilization of the N-terminal domain enables rapid spider silk formation.
Kronqvist N, Otikovs M, Chmyrov V, Chen G, Andersson M, Nordling K, et al
Nat Commun 2014 ;5():3254

High-resolution structure of a BRICHOS domain and its implications for anti-amyloid chaperone activity on lung surfactant protein C.
Willander H, Askarieh G, Landreh M, Westermark P, Nordling K, Keränen H, et al
Proc. Natl. Acad. Sci. U.S.A. 2012 Feb;109(7):2325-9

Self-assembly of spider silk proteins is controlled by a pH-sensitive relay.
Askarieh G, Hedhammar M, Nordling K, Saenz A, Casals C, Rising A, et al
Nature 2010 May;465(7295):236-8

Pulmonary surfactant-associated polypeptide C in a mixed organic solvent transforms from a monomeric alpha-helical state into insoluble beta-sheet aggregates.
Szyperski T, Vandenbussche G, Curstedt T, Ruysschaert JM, Wüthrich K, Johansson J
Protein Sci. 1998 Dec;7(12):2533-40