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  Maria Mota Profile

 

 

Research Focus:

While hepatocyte-Plasmodium interactions during liver stages constitute an ideal target for prophylactic intervention strategies, the blood stages of infection constitute the ultimate goal for therapeutic strategies against the disease. Our overall goal is to elucidate the role of host components in the establishment of a malaria infection (liver stage) as well as in the development of pathology (blood stage).

Thus, we aim to exploit the post-genome knowledge of the host in order to understand the requirements that govern Plasmodium development inside the hepatocyte. The marked preference of Plasmodium for hepatocytes relative to other cell types suggests that the host cell strongly influences the parasite’s development and, ultimately, the fate of infection. By applying microarray analysis and a systematic RNA interference (RNAi) screen of host factors, we are determining a number of host molecules affecting proper parasite invasion and/or development. Since the combined activities of kinases and phosphatases can tightly control numerous cellular processes, it seems logical to assume that they can modulate the cell’s behavior following infection by an intracellular pathogen. Thus, we also used RNAi to selectively knock-down the expression of 727 genes in the human genome, encoding all the known proteins with putative kinase activity, as well as several kinase-interacting proteins. We have determined a number of host molecules affecting proper parasite development. We now propose to determine the mechanisms behind this effect.

In addition, using rodent models of malaria, we aim to elucidate the role of certain host factors in the establishment of pathology. Although the nature of the pathogenic processes leading to severe malaria is poorly understood, activation of microvascular endothelial cells, producing a series of pro-inflammatory molecules, seems to play a pivotal role. We have shown that activation of heme oxygenase 1 (HO-1), a so called “protective gene” because it controls the extent of an inflammatory response, protects mice from severe malaria. We now propose to elucidate the role of HO-1 and its products in the course and pathology of malaria.

 

 

 

Lab details :

 

Group Leader:

Maria M Mota

Email:

mmota@fm.ul.pt

Address:

Instituto de Medicina Molecular, Unidade de Malária, Av. Prof. Egas Moniz, 1649-028 Lisboa

City:

Lisboa

Country:

Portugal

Telephone:

351 21 799 9509

Fax:

351 21 799 9504

Institution:

Instituto de Medicina Molecular

Homepage:

http://www.imm.ul.pt/indexi.html