The Bernardes laboratory works at the interface of chemistry and biology with a focus on protein chemistry and targeted cancer therapeutics.
Nature has produced an intricate machinery to covalently diversify the structure of proteins after their synthesis in the ribosome. At the core of our research and in an attempt to mimic nature, we are engineering reactions that allow for post-expression modification of proteins at selected sites. We use such reactions to selectively install particular modifications on proteins for many biological and therapeutic applications. For example, we are developing strategies for site-selective protein labelling in live cells by combining the introduction of small-sized non-proteinogenic tagged amino acids with very rapid chemoselective reactions. We aim to apply these to label and monitor disease-associated proteins under native conditions without interfere with the protein’s innate structure, function, activity and localisation as well as cellular functions.
Another important aspect of protein modification is for example the conjugation of cytotoxic molecules to antibodies to improve efficacy and reduce side effects of cancer treatments. Gonçalo’s laboratory is engineering new reactions that can be performed site-selectively on native antibodies, i.e. without the need for sequence engineering.
These are two examples among other lines of research in our lab that have in common the use of synthetic aqueous chemistry to address challenges in biology and medicine. Our ultimate goal is to see the widespread use of our findings and methodologies by other laboratories around the world and to directly assist in the design and discovery of new drugs with improved selectivity and efficacy for treating cancer.
Recent News
June 2024
We are thrilled to announce that Professor Gonçalo Bernardes has been awarded the prestigious 2024 Corday-Morgan Mid-Career Prize for Chemistry. His groundbreaking work in targeted therapeutics, including small molecule-based RNA degradation and the conditional activation of chemotherapeutics, has earned him this honour. Professor Bernardes attributes this achievement to the dedication and talent of his students, colleagues, and family. We celebrate his contributions to advancing human health through innovative chemistry. Full details about the award can be found here.
May 2023
Congratulations to Gonçalo, who has been recognised by the European Federation for Medicinal Chemistry and Chemical Biology with the EFMC-WuXi AppTec Award for Excellence in Chemical Biology.
Gonçalo's remarkable research in developing a new strategy for 'hijacking' and degrading RNA, dubbed meCLICK-Seq, is recognised in this award. Full details about the award can be found here.
May 2023
Our new work describing small molecules that degrade genomes of SARS-CoV-2 has been
published in ACS Central Science and highlighted in several media, including Fierce Biotech. This study describes a method to convert RNA binders into degraders, which are utilised to target two RNA structures in the
genome of SARS-CoV-2. These molecular constructs are demonstrated to degrade their targets and
exert anti-SARS-CoV-2 effects in a number of model systems.
January 2023
Our work on discovering Piperlongumine as a SARS-CoV-2 host-directed antiviral has been published in ACS Central Science and highlighted in EurekAlert and MedicalExpress, here. This study reveals that Piperlongumine selectively induces an increase in ROS levels in infected cells and significantly inhibits disease progression in a mouse model. It provides a new approach to combat SARS-CoV-2 variants and even other viruses. Check out the EurekAlert and Medical Express articles and our research paper.
June 2022
Our new method that ‘masks’ cancer-killing drugs and avoids harming healthy cells has now been published!This new approach uses a molecular carrier to deliver ortho-quinones directly to specific cells and shield healthy cells from the drug. You can read a News & Views about our work, here, and news article about our work here. If you want to learn more, you can read the full article in Nature Chemistry, here.
June 2022
Congratulations to Gonçalo who has been promoted to Full Professor at the Yusuf Hamied Department of Chemistry, University of Cambridge.
Gonçalo is very grateful for the talent and hard-work of all of the undergraduate students, graduate students, postdoctoral researchers, and collaborators that he has worked with, and for the support from his family.
January 2022
Many congratulations to Gonçalo who has been named as a finalist for the 2022 Blavatnik Awards UK. The Blavatnik Awards for Young Scientists celebrate the achievements and potential of young faculty and their innovative research. Gonçalo's work in the area of ‘bench-to-clinic’ bioorthogonal chemistry is recognised in this award. Full details about the award and this years’ winners can be found here.
November 2021
Our work in collaboration with Prof. Tuomas Knowleson how shear forces affect the rates of biomolecular reactions has been highlighted by Derek Lowe on his In The Pipeline blog, in Nature Chemical Biology and in Chemistry World. Our latest method uses biophysically mimetic microfluidic reactors to model the shear stresses that occur in capilliaries and the resultant effects on reactions and protein structure. Check out Derek's article, the Nature Chemical Biology article, the Chemistry Worldarticle and our research paper.
April 2021
Our work in collaboration with Prof. Vera Moiseenkova-Bell from the Perelman School of Medicine, US, on allosteric antagonist modulation of TRPV2 by piperlongumine to impair progression of glioblastoma has been highlighted in EurekAlert! and Público.
Our latest method uses advanced computer modelling to identify targets for natural products with anticancer properties. This work uses piperlongumine to treat an aggressive brain cancer, glioblastoma, and initial results in mice have been exceptionally positive. Check out the EurekAlert! and Público (in Portuguese) articles and our research paper.
February 2021
Congratulations to our many recent fellowship awardees. Many congratulations to Drs Cong Tang, Enrique Gil de Montes, Yanira Mendez and Luís Carvalho on being awarded Marie Sklodowska Curie Fellowships. Also to Dr Michael Geeson on being awarded an EMBO Fellowship and to Dr Daniel Zaidman for being awarded a Blavatnik Fellowhsip. We look foward to working with you all as part of your new fellowships later this year.
Interested in joining the GBernardesLab?
We are always looking for enthusiastic and bright researchers to join the Bernardes Lab. The groups research is multidisciplinary and involves synthetic chemistry, design & protein expression, conjugation chemistry, bioimaging, and therapeutic evaluation in vivo. If you are interested in joining the group, either as a Masters or PhD student, or as a Postdoctoral Researcher, please contact Gonçalo directly at gb453@cam.ac.uk.
All applications should include a cover letter that highlights your research interests, a full CV, and the names and addresses of two referees. Funded PhD and Postdoctoral positions will be advertised when available through the university jobs portal. Postdoctoral researchers are encouraged to obtain their own fellowships.
Potential funding sources include:
Royal Society Newton International Fellowships
Fundação para a Ciência e a Tecnologia
Human Science Frontier Programme