Molecular and Cellular Basis of Bacterial Pathogenicity
To understand the cellular and molecular bases of bacterial-host interaction, we work on the following fronts: We compare the genome data of bacteria isolated from patients, originating from different conditions (vaccination status of the patient, symptoms/disease evolution, age/sex, location/date, etc.), in search of evolutionary and epidemiological patterns of infection. We also study in vitro and in vivo aspects related to colonization, invasion and evasion of the host's immune system presented by bacteria of the genus Leptospira. We characterize the virulence factors and pathogenicity mechanisms of intestinal and extraintestinal Escherichia coli pathotypes.
Search for possible drugs to fight parasitic diseases through the study of DNA metabolism and epigenomics
In this line of research we study the DNA metabolism (DNA replication and repair) and the epigenetics (hitone modifications and histone modifying enzymes) of the parasites Trypanosoma cruzi, Trypanosoma brucei and Schistosoma mansoni. This line aims to understand how the genome and epigenome contribute to the success of the infection caused by these organisms, which have an important medical appeal in Latin America. In the search for effective drugs against S. mansoni, we studied the in vitro effect of histone-modifying enzyme inhibitors on the parasite's survival, both in pairs of paired and mismatched adult worms and in schistosomules. Pairing loss and decreased egg laying are two phenotypic parameters used to monitor the effect of drugs. Furthermore, we measure large-scale gene expression by RNA-seq in the parasite treated with histone-modifying enzyme inhibitors to characterize the affected gene networks and the affected metabolic pathways, and identify in these networks the possible altered genes that are new targets for testing other drugs that are candidates for synergistic effects.
Immune Response in Infection
We study the molecular mechanisms involved in the action of molecules on innate and adaptive immune responses. We evaluate the regulation of antibody production and mechanisms that regulate their effector function in patients and in wild or genetically selected mouse models. Among the studied immune responses, we mention the following: immune response to bacterial anatoxins (Tetanus, Botulinum types A,B,E, Diphtheria), response to different antigens associated with new adjuvants, immune response of patients to arbovirus infections. We also use Crotoxin (CTX), a toxin isolated from rattlesnake venom, as an important scientific tool capable of modulating the metabolism of macrophages (MØs) to highlight key points of cellular metabolism involved in the training of the immune system.
Development of Bacterial and Viral Vaccines
This line of research aims at (i) the development of bioprocesses for the production of vaccine antigens and (ii) the development of vaccines and (iii) the development of a vaccine quality control methodology. Among the antigens studied are the capsular polysaccharides of Streptococcus pneumoniae, recombinant pneumococcal proteins (pneumococcal surface protein A, pneumolysin and hybrids of these two molecules) and surface antigen of the hepatitis B virus. We studied methods of chemical conjugation of bacterial capsular polysaccharides to carrier proteins and carrier proteins and the evaluation of the potential of these conjugates as vaccine candidates. The vaccines that have been developed are recombinant BCG vaccines against Bordetella pertussis, Streptococcus pneumoniae and Schistosoma mansoni. For the quality control of serums and vaccines, we apply microbiological methodologies for the detection of contaminants in immunobiologicals. We also study the stability of serums and vaccines and the effectiveness of preservatives used as preservatives in serums and vaccines
Diagnosis of viral and bacterial diseases
This line of research aims to develop diagnostic methods and prevention policies in health care based on the following objectives: a) development of diagnostic devices and methodologies for the identification of infectious diseases caused by microorganisms; b) creation of management and georeferencing softwares for diseases caused by microorganisms for both private and public sectors and c) diagnostic accessibility and innovation.