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Centre for Misfolding Diseases

Gabriella (Gabi) Heller is the Rosalind Franklin Research Fellow at Newnham College. Her research focuses on intrinsically disordered proteins, biomolecules lacking a single, rigid three-dimensional structure that instead exist as a dynamic equilibrium of conformationally distinct states. These proteins are highly prevalent in diseases such as dementia and cancer, yet are often considered therapeutically 'untargetable' as they are unamenable to traditional drug discovery techniques.  Gabriella aims to understand whether and how intrinsically disordered proteins can be targeted by small molecule therapeutics using a combination of computational and experimental techniques. 

Publications

Thermodynamic and kinetic design principles for amyloid-aggregation inhibitors.
TCT Michaels, A Šarić, G Meisl, GT Heller, S Curk, P Arosio, S Linse, CM Dobson, M Vendruscolo, TPJ Knowles
– Proceedings of the National Academy of Sciences of the United States of America
(2020)
117,
24251
Rational design of a conformation-specific antibody for the quantification of A beta oligomers
FA Aprile, P Sormanni, M Podpolny, S Chhangur, L-M Needham, FS Ruggeri, M Perni, R Limbocker, GT Heller, T Sneideris, T Scheidt, B Mannini, J Habchi, SF Lee, PC Salinas, TPJ Knowles, CM Dobson, M Vendruscolo
– Proceedings of the National Academy of Sciences
(2020)
117,
13509
A kinetic ensemble of the Alzheimer’s Aβ peptide
T Löhr, K Kohlhoff, G Heller, C Camilloni, M Vendruscolo
(2020)
Trodusquemine enhances A beta(42) aggregation but suppresses its toxicity by displacing oligomers from cell membranes
R Limbocker, S Chia, FS Ruggeri, M Perni, R Cascella, GT Heller, G Meisl, B Mannini, J Habchi, TCT Michaels, PK Challa, M Ahn, ST Casford, N Fernando, CK Xu, ND Kloss, SIA Cohen, JR Kumita, C Cecchi, M Zasloff, S Linse, TPJ Knowles, F Chiti, M Vendruscolo, CM Dobson
– Nat Commun
(2019)
10,
225
Small molecule sequestration of amyloid-β as a drug discovery strategy for Alzheimer’s disease
G Heller, F Aprile, T Michaels, R Limbocker, M Perni, FS Ruggeri, B Mannini, T Löhr, M Bonomi, C Camilloni, A De Simone, I Felli, R Pierattelli, T Knowles, C Dobson, M Vendruscolo
(2019)
Promoting transparency and reproducibility in enhanced molecular simulations
PLUMED consortium
– Nature Methods
(2019)
16,
670
Determination of Structural Ensembles of Proteins: Restraining vs Reweighting
R Rangan, M Bonomi, GT Heller, A Cesari, G Bussi, M Vendruscolo
– Journal of chemical theory and computation
(2018)
14,
6632
Structural Ensemble Modulation upon Small-Molecule Binding to Disordered Proteins.
GT Heller, M Bonomi, M Vendruscolo
– Journal of molecular biology
(2018)
430,
2288
Multistep Inhibition of α-Synuclein Aggregation and Toxicity in Vitro and in Vivo by Trodusquemine
M Perni, P Flagmeier, R Limbocker, R Cascella, FA Aprile, C Galvagnion, GT Heller, G Meisl, SW Chen, JR Kumita, PK Challa, JB Kirkegaard, SIA Cohen, B Mannini, D Barbut, EAA Nollen, C Cecchi, N Cremades, TPJ Knowles, F Chiti, M Zasloff, M Vendruscolo, CM Dobson
– ACS Chem Biol
(2018)
13,
2308
Methods of probing the interactions between small molecules and disordered proteins
GT Heller, FA Aprile, M Vendruscolo
– Cellular and molecular life sciences : CMLS
(2017)
74,
3225
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01223 763845 (shared)

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