Jan Johansson



Research group:

Medical Protein biochemistry (Jan Johansson)

Research interests:

My research has resulted in

  • a drug for treatment of neonatal lung disease
  • discovery of the first chaperone domain that specifically prevents amyloid toxicity
  • development of biomaterials and biotech tools based on spider silk and its formation


Lung surfactant protein C (SP-C) and treatment of respiratory distress syndrome (RDS)

SP-C is essential for treatment of RDS but it is the most hydrophobic polypeptide identified, making it difficult to study. In spite of this we have determined its atomic-resolution structure and found that the SP-C α-helix forms β-sheet aggregates as soon as it unfolds. This suggested an explanation to the aggregation encountered when synthesizing SP-C – the helical state is simply not reached before insoluble aggregates are formed. We solved this problem by an innovative approach; replacing all residues in SP-C with high β-sheet propensity yielded a thermodynamically stable peptide. This SP-C analogue can be synthesized in large amounts without aggregation, is active in animal models of RDS, and treatment of >20 premature infants with RDS show that is works well in clinical practice.

The first anti-amyloid chaperone

The SP-C helix is built from residues with very high tendency to form a β-sheet, and we observed the same phenomenon in the amyloid β-peptide (Aβ) associated with Alzheimer’s disease and the prion protein. The inability of the SP-C α-helix to form in vitro raised questions about its formation in vivo. We discovered that a BRICHOS domain in the SP-C precursor works as a molecular chaperone that prevents aggregation of the SP-C part. Intriguingly, mutations that segregate with human lung fibrosis are localized to the BRICHOS domain, and our determination of the first structure of a BRICHOS domain explained how mutations inactivate its chaperone function and lead to amyloid disease. From the similar features of SP-C and Ab we hypothesized that BRICHOS can prevent Aβ fibrillation and toxicity, and we have confirmed that BRICHOS blocks Aβ toxicity inDrosophila CNS and in mouse hippocampal slices. We have elucidated the molecular mechanism behind BRICHOS reduction of Aβ42 toxicity; it blocks secondary nucleation and thereby reduces the amounts of toxic Aβ42 oligomers by >80%.

From molecular mechanisms in spider silk formation to novel biomaterials and drug carriers

The main components of spider silk are spidroins - large and repetitive proteins with conserved terminal domains (NT and CT). Spiders manage to store the highly aggregation-prone spidroins in solution at extreme concentrations and to rapidly convert them into a solid fiber within fractions of a second. We have explored in detail how NT and CT regulate spidroin solubility and silk formation under physiological conditions, explaining how precocious spidroin aggregation is prevented, and how temporal and spatial control of silk formation is achieved. These insights have enabled us to produce artificial spider silk scaffolds for growth and differentiation of pluripotent stem cells. Moreover, an NT solubility tag for recombinant protein production has been developed, and our SP-C analogue can now be produced so efficiently that we will use it to develop artificial surfactant for drug delivery.


Anna Rising, Marlene Andersson, Yizhong Zhou