Throughout her career Mota has researched the molecular biology of malaria infection, especially regarding host-pathogen interactions. Although she studies molecular interactions her research has linked these to grander host factors which influence infection, such as nutrition status and circadian rhythms. Mota was the lead researcher of the first study to demonstrate that malaria parasites, when they enter the liver early in infection, enter and traverse through multiple liver cells before finding a cell that they stay in for replication. This work was based on a serendipitous discovery made from a conversation between Mota and Ana Rodriguez in a lift, about an old film Rodriguez had from a previous research project. The work was another example of collaboration between Victor and Ruth Nussenzweig. Mota’s research has often investigated the liver stage of malaria, an oft-forgotten stage of the parasite, but an important one since it is the first stage of infection after mosquito bite. Mysteriously immunity to this part of the malaria life cycle is very poor. Mota was involved in a study which showed that this is partially a consequence of the repression of Dendritic cells in the liver, which normally activate T cells and present them with the molecular targets of the infection. However she later showed that the liver does possess an active innate immune system response. Malaria cells further protect themselves from destruction by the liver cells themselves by binding the autophagy factor Microtubule-associated protein light chain 3. This research opens up a new therapeutic target for malaria drugs. Mota’s own research group showed that an ongoing blood stage infection inhibits a new malaria liver stage. This works through the action of hepcidin, which is upregulated during malaria infection and diverts iron away from liver cells, starving a new malaria infection of an essential nutrient. In 2017 Mota’s team published research indicating that malaria parasites are able to sense the nutritional status of their host and correspondingly alter their growth rates. 30% calorie restriction diets of laboratory mice lead to a reduction in growth rate of Plasmodium berghei parasites in the mice blood. A malaria kinase protein, KIN, was found to be involved in sensing host nutritional status, as when it was genetically knocked-out of the parasites they did not respond to host calorie restriction. These results match evidence from human infections, as doctors had noticed that malaria infections sometimes get more severe after hospitalisation and improved feeding of malnourished patients.
Awards
In 2003 Mota was given a Young Investigator Award by EMBO. More funding came from a European Science Foundation Young Investigator award in 2004. In 2005 Mota was appointed Commander of the Order of Prince Henry, a national honour of Portugal. She was honored with the Prémio Pessoa Prize in 2013, given to Portuguese citizens who contribute significantly to the arts or sciences. Mota is one of the youngest recipients of the prestigious award. In November 2017 she was awarded the Pfizer Prize for her work in the area of malaria. In November 2018 she received the mid-career Sanofi-Institut Pasteur prize, worth 150 thousand euros.
