As any other obligate parasite, Plasmodium depends on its hosts and on the nutrients they provide to survive and complete its life cycle. Surprisingly, nothing is know about Plasmodium’s capacity to sense nutrients or its host’s nutritional status and thereby reprogram its metabolism. Our preliminary data provides unequivocal evidence that Plasmodium has the ability to sense the host low-nutrient status and adapt to it by decreasing its multiplication rate. Thus, the overall goal of the present proposal is to unveil the molecular mechanisms by which parasites are capable to sense and adapt to environmental signals originated from nutrients and to determine its impact on the course and virulence of infection. To that end we propose to: (i) Identify Plasmodium pathway(s) that sense (host) nutritional changes; (ii) Uncover which molecules are sensed by Plasmodium during its intracellular development; (iii) Study the impact of the parasite’s nutrient sensing pathways activity on the course of infection; and (iv) Evaluate host nutritional status sensing as a common feature in parasites. The present proposal moves towards a change of paradigm on how host-parasite interactions are viewed. By definition, since a parasite requires a host in order to survive, a decrease in the availability of an essential molecule obtained from the host will weaken the parasite and render it incapable of succeeding in its life cycle. The rationale behind this proposal is that parasites monitor host nutritional environment and, prior to any nutrient(s) becoming limiting, are able to respond and adapt to the sensed alteration(s). Multidisciplinary approaches that combine genetic, genomic, cell biological and physiological methodologies will be used. Results arising from the present proposal will provide novel insights into the cell biology of these parasites and will increase our understanding of the interactions that these parasites maintain with their hosts.