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Centre for Misfolding Diseases

Dr Johnny Habchi

Educational background

I completed my BSc in Biochemistry at the Lebanese University during which I became interested in understanding the protein folding process. In order to pursue my interests, I joined an MSc programme in Aix-Marseille University, France, where I studied the folding of unstructured proteins, namely intrinsically disordered proteins.

My research during my MSc and PhD was centred on understanding the molecular mechanisms by which the folding of disordered proteins upon binding to their partners results in the gain of a function, which leads in some cases to human diseases. In particular, I studied the role of intrinsically disordered proteins in orchestrating the replicative machinery of RNA virsues.

Current research

After my PhD, I joined the Centre for Misfolding Diseases, where my research to date mainly focuses on the generation of new methods that allow the detailed understanding of the molecular principles underlying the misfolding of intrinsically disordered proteins, a hallmark of many diseases, such as Alzheimer’s and Parkinson’s diseases, for the aim of drug discovery.

At the Centre, I have worked on elucidating the fundamental principles of protein aggregation and on developing quantitative tools for the assessment of the efficacy of drug molecules in modulating the protein aggregation process. In collaboration with many colleagues and based on the accumulated knowledge in the Centre, we have set up an innovative and interdisciplinary drug discovery programme that aims at the selective targeting of specific microscopic processes in a controlled intervention during the aggregation of proteins associated with misfolding diseases, in particular Alzheimer’s and Parkinson’s diseases. A direct consequence of this endeavour was the ability to reach, for the first time, a detailed understanding of the mode of action of drug molecules on single microscopic steps during the aggregation process.

Research translation

This contribution has led to the translation of the drug discovery programme into practice by creating Wren Therapeutics, a biopharmaceutical company, in which I am currently the Head of R&D. Wren Therapeutics aims at bridging the gap between fundamental and translational research in order to generate transformative treatments across a wide range of protein misfolding diseases.


AFM-Based Single Molecule Techniques: Unraveling the Amyloid Pathogenic Species
FS Ruggeri, J Habchi, A Cerreta, G Dietler
– Current pharmaceutical design
A Fragment-Based Method of Creating Small-Molecule Libraries to Target the Aggregation of Intrinsically Disordered Proteins
P Joshi, S Chia, J Habchi, TPJ Knowles, CM Dobson, M Vendruscolo
– ACS Comb Sci
Neuroscience: An anticancer drug suppresses the primary nucleation reaction that initiates the production of the toxic Ab42 aggregates linked with Alzheimer's disease
J Habchi, P Arosio, M Perni, AR Costa, M Yagi-Utsumi, P Joshi, S Chia, SIA Cohen, MBD Müller, S Linse, EAA Nollen, CM Dobson, TPJ Knowles, M Vendruscolo
– Sci Adv
Dynamics of the Intrinsically Disordered C-Terminal Domain of the Nipah Virus Nucleoprotein and Interaction with the X Domain of the Phosphoprotein as Unveiled by NMR Spectroscopy
L Baronti, J Erales, J Habchi, IC Felli, R Pierattelli, S Longhi
– ChemBioChem
Structural disorder within paramyxoviral nucleoproteins and phosphoproteins in their free and bound forms: From predictions to experimental assessment
J Habchi, S Longhi
– International Journal of Molecular Sciences
Neuronal Cx3cr1 Deficiency Protects against Amyloid β-Induced Neurotoxicity
J Dworzak, B Renvoisé, J Habchi, EV Yates, C Combadière, TP Knowles, CM Dobson, C Blackstone, O Paulsen, PM Murphy
The inverted free energy landscape of an intrinsically disordered peptide by simulations and experiments
D Granata, F Baftizadeh, J Habchi, C Galvagnion, A De Simone, C Camilloni, A Laio, M Vendruscolo
– Scientific reports
Order and Disorder in the Replicative Complex of Paramyxoviruses
J Erales, D Blocquel, J Habchi, M Beltrandi, A Gruet, M Dosnon, C Bignon, S Longhi
– Advances in experimental medicine and biology
Molecular Basis for Structural Heterogeneity of an Intrinsically Disordered Protein Bound to a Partner by Combined ESI-IM-MS and Modeling
A D'Urzo, A Konijnenberg, G Rossetti, J Habchi, J Li, P Carloni, F Sobott, S Longhi, R Grandori
– J Am Soc Mass Spectrom
Dynamics of the intrinsically disordered C-terminal domain of the nipah virus nucleoprotein and interaction with the X domain of the phosphoprotein as unveiled by NMR spectroscopy
L Baronti, J Erales, J Habchi, IC Felli, R Pierattelli, S Longhi
– Chembiochem : a European journal of chemical biology
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01223 336427 (shared)

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