Where Ideas grow

Molecular Parasitology

ABOUT

Research performed by the Molecular Parasitology (MP) group focuses on trypanosomatids of the genus Leishmania, agents of leishmaniasis. Our aim is to elucidate fundamental aspects of the biology of these parasites and of their interaction with mammalian hosts. We employ a multidisciplinary approach combining molecular, cell biology and biochemistry methodologies. 

 

Aims:

1. Trypanosomatid peroxiredoxins (PRXs) are virulence factors whose crucial function is ascribed to their peroxidase activity. However, our lab has shown that their essentiality is unrelated to antioxidant protection. We are exploring new functions for these enzymes by i) deciphering the molecular basis and physiological relevance of the recently disclosed chaperone activity of the mitochondrial PRX and ii) investigating the involvement of cytosolic PRXs in H2O2-mediated signaling and how this contributes to parasite infectivity.

2. Mitochondrial oxidation of NADH is a key process in all organisms. In trypanosomatids it utilizes enzymes that are absent from mammals. We are functionally characterizing two of these unique enzymes (NADH dehydrogenase and fumarate reductase) in Leishmania.

3. Leishmania compete with their hosts for nutrients, metals included. We are investigating zinc and iron metabolism in these parasites. For this, we are i) identifying proteins involved in zinc and iron acquisition and studying their regulation by metal bioavailability, and ii) analyzing whether Leishmania modulates the expression of zinc and iron host metabolism proteins as a means to gain access to these essential metals.

 

 

RESEARCH

The MP group has contributed significantly to the current state of knowledge about the distinctive redox biology of Leishmania and related trypanosomatids. Our investigation led to several published discoveries, often with intra- and extramural collaborations, and also to invitations to authorship reviews in high-ranked journals (e.g. Antioxid Redox Signal) and in books, as well as to communicate our findings in scientific meetings (e.g. Gordon Research Conferences). 

Main achievements:

1. Assignment of a novel chaperone function to the mitochondrial peroxiredoxin that is crucial for Leishmania infectivity (Castro et al. 2011; Teixeira et al., 2015).

2. Reassessment of the pre-established model by which reducing power is supplied to mitochondrial redox pathways (Castro, Romao et al. 2010).

4. Genetic validation of several Leishmania enzymes as targets for chemotherapy (Romao et al. 2009; Castro et al. 2011; Sousa et al, 2014)

5. Identification of the first mediator of zinc internalization and homeostasis in Leishmania (Carvalho, et al. 2015)

6. Delivery of computer software and algorithm for automatic determination of Leishmania infection indexes (http://cellnote.up.pt/; Neves et al. 2014).

This immunofluorescence micrograph shows a small section of a mouse liver infected with Leishmania infantum parasites. Nuclei are visualized in blue and parasites in green.