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Centre for Misfolding Diseases

Gonçalo Bernardes is a Professor of Chemical Biology & a Fellow of Trinity Hall College, Cambridge.

What we do

Nature has its own machinery for modifying the structure of proteins. In our research, we’re attempting to mimic this machinery to gain significant therapeutic benefits. We’re engineering chemical reactions that enable us to modify proteins while allowing to choose the precise location in the protein’s structure where we want to install these modifications.

This work has a whole range of applications. For example, we’re currently developing ways of selectively labelling proteins in living cells: this can help us monitor the proteins associated with particular diseases without interfering either with the protein’s structure, function, activity and location or upsetting the cell’s normal functions. Another important potential application for this work is linking cytotoxic drug molecules (molecules that are poisonous to cells) to antibodies and then using the antibody to deliver the drug in a very targeted way to the diseased tissue. This could improve the effectiveness of cancer treatments and reduce their side effects.

These are two examples from among our lines of research that use site-selective and bioorthogonal chemistry to address challenges in biology and medicine. We hope our methods may in future be used in laboratories around the world to help develop new drugs with improved effectiveness and reduced side-effects for some of the most common diseases such as cancer.

Funding

We are funded by the Royal Society, by UKRI (EPSRC) and by the European Commission (Marie Sklodowska Curie actions & European Research Council)

For further information on our research and for opportunities, please check our research group website.

Watch Dr Bernardes discuss his research

Take a tour of the Bernardes Lab

Publications

Cysteine‐Assisted Click‐Chemistry for Proximity‐Driven, Site‐Specific Acetylation of Histones
CF Afonso, MC Marques, JPM António, C Cordeiro, PMP Gois, PMSD Cal, GJL Bernardes
– Angewandte Chemie
(2022)
134,
Fragment-based computational design of antibodies targeting structured epitopes
M Aguilar Rangel, A Bedwell, E Costanzi, RJ Taylor, R Russo, GJL Bernardes, S Ricagno, J Frydman, M Vendruscolo, P Sormanni
– Sci Adv
(2022)
8,
eabp9540
Selective Inhibition of Bruton's Tyrosine Kinase by a Designed Covalent Ligand Leads to Potent Therapeutic Efficacy in Blood Cancers Relative to Clinically Used Inhibitors.
BB Sousa, CR de Almeida, AF Barahona, R Lopes, A Martins-Logrado, M Cavaco, V Neves, LAR Carvalho, C Labão-Almeida, AR Coelho, M Leal Bento, RMRM Lopes, BL Oliveira, MARB Castanho, P Neumeister, A Deutsch, GI Vladimer, N Krall, C João, F Corzana, JD Seixas, R Fior, GJL Bernardes
– ACS pharmacology & translational science
(2022)
5,
1156
Cysteine‐Assisted Click‐Chemistry for Proximity‐Driven, Site‐Specific Acetylation of Histones
CF Afonso, MC Marques, JPM António, C Cordeiro, PMP Gois, PMSD Cal, GJL Bernardes
– Angewandte Chemie International Edition
(2022)
61,
e202208543
Chemical and Enzymatic Methods for Post-Translational Protein–Protein Conjugation
RJ Taylor, MB Geeson, T Journeaux, GJL Bernardes
– J Am Chem Soc
(2022)
144,
14404
π‑Clamp-Mediated Homo- and Heterodimerization of Single-Domain Antibodies via Site-Specific Homobifunctional Conjugation
RJ Taylor, M Aguilar Rangel, MB Geeson, P Sormanni, M Vendruscolo, GJL Bernardes
– Journal of the American Chemical Society
(2022)
144,
13026
Controlled masking and targeted release of redox-cycling ortho-quinones via a C-C bond-cleaving 1,6-elimination.
L Dunsmore, CD Navo, J Becher, EG de Montes, A Guerreiro, E Hoyt, L Brown, V Zelenay, S Mikutis, J Cooper, I Barbieri, S Lawrinowitz, E Siouve, E Martin, PR Ruivo, T Rodrigues, FP da Cruz, O Werz, G Vassiliou, P Ravn, G Jiménez-Osés, GJL Bernardes
– Nature Chemistry
(2022)
14,
754
Platform for Orthogonal N-Cysteine-Specific Protein Modification Enabled by Cyclopropenone Reagents
A Istrate, MB Geeson, CD Navo, BB Sousa, MC Marques, RJ Taylor, T Journeaux, SR Oehler, MR Mortensen, MJ Deery, AD Bond, F Corzana, G Jiménez-Osés, GJL Bernardes
– J Am Chem Soc
(2022)
144,
10396
The Impact of Activity‐Based Protein Profiling in Malaria Drug Discovery
LAR Carvalho, GJL Bernardes
– ChemMedChem
(2022)
17,
e202200174
Structural insights into TRPV2 activation by small molecules.
G Lopes Bernardes, R pumroy, A Protopopova, T Fricke, I Lange, F Haug, P Nguyen, P gallo, B sousa, V yarov-yarovoy, A leffler, V moiseenkova-bell
– Nature Communications
(2022)
13,
2334
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Group Leader

Research Interest Groups

Telephone number

01223 336305

Email address

College

Trinity Hall