By means of a multidisciplinary approach, we study the biochemical, structural and biological features that distinguish several key components of the redox system from pathogenic trypanosomatids, parasites that are causative agents of severe diseases in animals and humans (Chagas disease, Leishmaniasis and African sleeping sickness).
These studies allow us to identify and understand the role these components play in parasite biology (e.g. growth, infection, and pathogenesis).
Our research aims to gain understanding into the redox biology of trypanosomatids to guide novel strategies and the development of the safer and more efficacious drugs against this disease.
|Andrea Medeiros, PhD
|Mariana Bonilla, PhD
|Diego Benítez, PhD
|Estefanía Dibello, PhD
|Florencia Sardi, MSc
|María Victoria Gutiérrez
|Natalia Oddone, PhD
|Cristina Quiroga, MSc
Fundamental aspects of trypanothione metabolism: synthesis, reduction and utilization
We study the biochemical, structural and biological features that distinguish several key components of the trypanothione system from pathogenic trypanosomatids. Using animal infection models, we investigate the role these molecules play in parasite biology and pathogenesis. The data from these studies allows to validate new drug target candidates, their inhibitors as well as to guide novel drug development strategies.
Development of biosensors for non-invasive and high-content studies
Our laboratory is interested in the development of different types of biosensors (fluorescence- and luminescence-based) that allow the real time and non-invasive monitoring of parasite proliferation, redox state and major signaling pathways. The transgenic cell lines expressing the biosensors allow us to study the role played by the oxidative stress and redox signaling in a variety of cellular processes (e.g. host-pathogen interaction, cell differentiation, cell cycle, apoptosis and metabolic dysfunction). The reporter cell lines are also used in phenotypic drug-screening campaigns and to investigate drug mode of action.
Early phase drug discovery projects
We apply target- and phenotypic-based approaches to screen synthetic and natural compounds that affect, in a selective manner, the growth of the infective form of different trypanosomatid species. Drug repurposing is also an active area of research in our lab.
Drug mode of action at cellular and enzymatic level is addressed to foster and guide drug optimization. Our laboratory relies on an important network of local and international groups working on (medicinal) chemistry to fulfill this goal.
“Redox Chemistry and Biology of Thiols”-III International Theoretical and Practical Course. 18-28 February, 2019. Institut Pasteur Montevideo, Uruguay.
“International Course: Clinical Flow Cytometry”, Oct 1-5, 2018, Montevideo, Uruguay.
“VII International Course on Trypanosomatid Molecular”, Nov26-Dec1°, 2018, Montevideo, Uruguay.
“Theoretical and practical course on lab animals”, March 13-21, 2017, Montevideo, Uruguay.
“Cell and Animal Models for Drug Discovery”. Oct16-27, 2017, Montevideo, Uruguay.
“Integrating IP Montevideo technologies”, Sept8, 2017, Montevideo, Uruguay.
2019-2021 – Sinthesis and study of nuevos derivados de bensoisotiazolonas como agentes tripanosomátidos multiblanco. CSIC I+D 2018. Rol: co-responsable.
2019-2021 – QUINONAS MULTI-DIANA PARA EL DESARROLLO DE FÁRMACOS TRIPANOSOMICIDAS. CSIC I+D 2018. Rol: colaborador.
2019-2021 – Inferencia y Comparación de Modelos Cinéticos y Evolutivos de Cores Catalíticos de Proteasomas. CSIC I+D 2018. Rol: colaborador.
2019-2021 – Generación de extractos ricos en polifenoles a partir de orujos de uva. Alianza para la Innovación- Modalidad Desarrollo Tecnológico. ANII ALI_2_2018_1_149574. Rol: colaborador.
2018-2020 – “Structure-based design of chemical compounds against human pathogen parasites from the Trypanosomatida Order”. Deutsche Forschungsgemeinschaft (DFG or German research Agency) 2018-2020. Role: collaborator.
2015-2018 – Design of novel biosensors for simultaneous monitoring of redox and cAMP signalling: from the computer to the cell and back to the computer. Fondo María Viña, ANII, FMV_1_2014_1_104000. Role: collaborator.
2015-2017 – The thioredoxin-fold diversity in trypanosomatids and tapeworms. Project ICGEB CRP/URU 14-01–, 2015-2017. Role: co-responsible.
2015-2017 – Target-based drug discovery of compounds interfering with trypanothione biosynthesis in trypanosomatids. ACIP Grant – Project A-17-2015. Role: main responsible.
2014-2016 – Trypanosoma´s prostaglandin metabolism: role in infection, pathogenesis and drug resistance”, Fiocruz-Pasteur Grant. Role: main responsible.