Research
Our Research
Our lab conducts biomedical research directed to establish the metabolic strategies and host- pathogen relationship in bacterial pathogenic species, such as Chlamydia trachomatis, the most prevalent sexually transmitted disease in the world, and Vibrio cholerae, which produces severe gastrointestinal disease to millions of people in developing countries and in areas afflicted by natural disasters, where the availability of clean water is an issue.
Our research uses an interdisciplinary approach to study these topics, with diverse methodologies, such as molecular and structural biology, protein chemistry and cell biology. This strategy allows us to characterize deeply the behaviour of enzymes and understand molecular and subatomic aspects, such as electron movement and conformational changes, and apply these concepts to cell to cell relationships, disease development and drug design.
The aims of our research are:
1. Study the metabolic strategies and adaptations of pathogenic bacteria
2. Characterize the main metabolic enzymes and ion transporters in these parasites
3. Rationally design and characterize molecules can that inhibit these enzymes
Metabolic Strategies of Bacterial Pathogens
Summary
Our group is performing studies to understand the intricate regulation of the metabolism of pathogenic bacteria and its relationship with the host, in particular its metabolic and energetic dependencies. We are particularly interested to study the pathways used to generate energy, the metabolic strategies used by these bacteria in different stages of the infection cycle and how these parameters affect the production of virulence factors. The methodologies used in this part of our research include microbiological work with human pathogens under a biosafety level 2 environment, characterization of metabolic activities, by UV-vis spectroscopy, fluorometry and oximetry, and human cell culture methodologies, culturing pathogens in contact with the host cells.
Protein Engineering and Mechanistic Enzymology
Summary
The genomic data is essential to understand the strategies used by different microrganisms. However, a large number of biological aspects cannot be inferred directly from the genome sequence, especially functional, regulatory and systemic features of the metabolism. We are performing experiments to characterize the enzymes and proteins used by these bacteria to produce energy or transport essential nutrients. These studies involve the use of molecular biology techniques, to eliminate genes, clone them and overexpress these proteins. Moreover, the studies use heavily different protein chemistry and biochemical analysis, such as protein chromatography, enzyme kinetics, fast kinetics, NMR spectroscopy, Fluorometry, EPR and ENDOR spectroscopy, IR spectroscopy, among others.
Rational Drug Design
Summary
The massive use of antibiotics have triggered the rising in pathogenic bacteria that are resistant to multiple classes of these compounds. An essential part of our studies involve the rational design of new antibiotics, using the structural and mechanistic information of the enzymes involved in the metabolism of these bacteria, with the role that they play in their physiology. These studies require the use of diverse tools, such as metabolic analysis, enzyme kinetics, structural biology, pharmacology and molecular dynamics.
