Multicentric Program in Biochemistry and Molecular Biology

BIOCHEMISTRY OF PATHOLOGICAL STATES (BEP)

The study of chronic and degenerative diseases that allows the elucidation of biochemical routes that make up the integrating mechanisms of cellular signaling and can pave the way for the identification of therapeutic targets for various diseases.

Prof. Ana Claudia S. Tessis, PhD

Study of digitalis in the mechanism of reversion of the multiple resistance to drugs phenotype.

The research focus on the study of digitalis capable of inhibiting the activity of transporters responsible for multiple drug resistance. The importance of the study of these compounds lies in the fact that these inhibitors could be used to promote the reversal of the resistance phenotype observed in cells expressing those transporters. Thus, in combination, the currently available chemotherapeutics could once again be active and used in the treatment in which this type of phenotype is detected.

Prof. Eliezer Menezes Pereira, PhD

Study of the pathogenicity of coagulase-negative Staphylococcus.

Coagulase-negative Staphylococcus has increasingly appeared as agents of infection in humans and animals, especially the species S. epidermidis and S. haemolyticus. The focus of this line of research is to study the virulence factors of these microorganisms, prevalent clones and factors associated with the infections caused by them.

Prof. Juliene Antonio Ramos, PhD

Viral genetic diversity and protein interactions in the evolution of the natural history of HCV virus infection.

The line seeks to study the genetic diversity of HCV in patients aiming identify alterations related treatment resistance; in this scenario, new generation sequencing strategies are used. In addition, we sought to identify interaction partners of NS5a and NS5b that can help elucidate the natural history of HCV infection.

Prof. Luiz Dione Barbosa de Melo, PhD

Parasite-host interaction in Chagas' disease: participation of bioactive lipids and lectins.

The etiologic agent of Chagas disease, the protozoan Trypanosoma cruzi, is a parasite first identified in 1909 by Dr. Chagas. Because it is a debilitating and incurable disease, Chagas disease is still a serious public health problem, especially in the treatment of patients who have been infected in the past.The invasion of the vertebrate host by T. cruzi involves the steps of adhesion / recognition, signaling and invasion. During adhesion, there are innumerable interactions between receptors and / or host surface ligands with the parasite molecules, in a strain / evolution dependent form and specific cell type.

Different molecules and proteins participate in this process, such as lysophospholipids (e.g., lysophosphatidylcholine, which acts as a chemotactic signal for macrophages) and lectin proteins (e.g, ubiquitous Galectin-3, which recognizes β-galactosides present on the surface of the parasite through its CRD domain, facilitating infection in host cells and migration of the parasite into the extracellular matrix). However, the receptors and the signaling pathways involved in LPC-induced cell signaling and lectins exhibit a certain promiscuity with respect to the linker. For LPC has been proposed the interaction to TLR4 and TLR2 receptors, in addition to the G2A receptor (a G receptor coupled to the protein).

The lines of research propose to investigate the activation of cytoplasmic and nuclear signal transduction pathways in T. cruzi infection using in vitro models of ectopic expression of target proteins and in vivo models using knockout mice for TLR4, TLR2 and Galectin- 3. In summary, the investigation of these targets in the host-parasite interaction may contribute to a better understanding of the tissue pathophysiology in Chagas' disease. 

CELLULAR MEDIATORS (MC)

The study of cell signaling pathways that govern and coordinate cellular activities and functions in diverse conditions, such as cell division, growth and differentiation, cell-cell, extracellular matrix-cell and cell-nucleus-organelle surface interaction processes. Studies of the mediators involved in these processes, such as neurotransmitters, hormones, nucleotides, etc. Search for compounds with different activities, such as anti-parasitic, anti-microbial, anti-cancer, anticoagulants, etc.

Prof. Marcelo Alex de Carvalho, PhD

Functional studies of BRCA1 gene variants and the BRCT domain interaction proteins in DNA damage response.

The BRCA1 gene is associated with hereditary predisposition to breast and ovarian cancer, it encodes a protein, BRCA1, involved with mechanisms of DNA damage response (RDD), cell cycle control and transcription. Genetic variants of BRCA1 confer different degrees of risk on carrier. BRCA1 encloses BRCT domains in tandem in its C-terminal portion - this domain is the signature of several proteins involved with RDD. The main interest of our group is the development of functional study models of genetic variants of BRCA1 and also the study of proteins interacting with BRCT domains and their relationships with RDD mechanisms.