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Centre for Misfolding Diseases

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.

Publications

Cyanylated Cysteine used to Examine the NTAIL/XD Bound Complex of the Nipah Virus
SK Hess, H Yang, J Habchi, S Longhi, CH Londergan
– Biophysical Journal
(2013)
104,
234A
Mapping induced folding of viral nucleoproteins using SDSL combined with EPR spectroscopy
M Martinho, L Nesme, A Fournel, Z El Habre, J Habchi, S Longhi, B Guigliarelli, V Belle
– EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
(2013)
42,
S67
Interaction between the C‐terminal domains of measles virus nucleoprotein and phosphoprotein: A tight complex implying one binding site
D Blocquel, J Habchi, S Costanzo, A Doizy, M Oglesbee, S Longhi
– Protein Sci
(2012)
21,
1577
Assessing induced folding within the intrinsically disordered C-terminal domain of the Henipavirus nucleoproteins by site-directed spin labeling EPR spectroscopy.
M Martinho, J Habchi, Z El Habre, L Nesme, B Guigliarelli, V Belle, S Longhi
– J Biomol Struct Dyn
(2012)
31,
453
Transcription et réplication des Mononegavirales : une machine moléculaire originale.
D Blocquel, J-M Bourhis, J-F Éléouët, D Gerlier, J Habchi, M Jamin, S Longhi, F Yabukarski
– Virologie (Montrouge, France)
(2012)
16,
225
Monitoring Structural Transitions in IDPs by Vibrational Spectroscopy of Cyanylated Cysteine
H Yang, J Habchi, S Longhi, CH Londergan
– Methods in Molecular Biology
(2012)
895,
245
Monitoring structural transitions in IDPs by site-directed spin labeling EPR spectroscopy.
J Habchi, M Martinho, A Gruet, B Guigliarelli, S Longhi, V Belle
– Methods Mol Biol
(2012)
895,
361
Plasticity in Structural and Functional Interactions between the Phosphoprotein and Nucleoprotein of Measles Virus*
Y Shu, J Habchi, S Costanzo, A Padilla, J Brunel, D Gerlier, M Oglesbee, S Longhi
– The Journal of biological chemistry
(2012)
287,
11951
Structural disorder and induced folding within proteins of the replicative complex of paramyxoviruses
S Longhi, J Habchi, D Blocquel, S Blangy, M Blackledge, M Ringkjobing-Jensen
– FEBS JOURNAL
(2012)
279,
51
Compaction and binding properties of the intrinsically disordered C-terminal domain of Henipavirus nucleoprotein as unveiled by deletion studies.
D Blocquel, J Habchi, A Gruet, S Blangy, S Longhi
– Molecular BioSystems
(2011)
8,
392
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Research Staff Scientist

Telephone number

01223 336427 (shared)

Email address