One of the objectives pursued within this line of research is the study of the mode of action of the toxins from Bt to, in this way, be able to understand the mechanisms of resistance that the insects can generate against these toxins. This implies knowing the role of midgut proteases to render the active form of the protein, the characterisation of the membrane receptors, determining whether two or more toxins bind to the same binding sites, determining whether midgut cells react against the damaged infringed by the Bt toxins, etc. We are particularly interested in contributing to the detailed understanding of the mode of action of the Vip3 proteins, for which much less information is available compared with some of the best studied Cry proteins. Developing “binding sites models” is a very useful tool to determine which combinations of Bt proteins would not be advisable from the resistance management standpoint. The understanding of how two toxins interact in a particular pest allows us to make predictions on the possible appearance of cross-resistance to other Bt toxins. Two toxins that share the binding site in a membrane receptor can become simultaneously useless if the binding site changes by mutation. In that case both toxins, though different, would share a critical step in the mode of action and therefore its combination in the same Bt crop would be advised against. It is important to note that for this objective we do not require to work with resistant insects. Binding sites might involve a single membrane molecule or be the result of the interaction of more than one molecule. Furthermore, more than one binding site can be present in the same molecule. One of our goals is to characterise the membrane receptors and to determine the role they play in the toxicity of Bt proteins in different insect species. To validate that a putative receptor is a functional receptor we are using insect cultured cells as a model system. If a type of cells is not susceptible to a given Bt toxin, the transformation with the gene for a putative membrane receptor protein serves as a way to test its functionality. We have studied the mode of action of Bt toxins in many insect pests, all of them belonging to the Lepidoptera order. To mention just a few, we can list: Plutella xylostella (diamondback moth), Plodia interpunctella (Indianmeal moth), Trichoplusia ni (cabbage looper), Ostrinia nubilalis (corn borer), Heliothis virescens (tobacco budworm), Helicoverpa armigera, Helicoverpa zea, Phthorimaea operculella (potato tuber moth), Mamestra brassicae, Spodoptera frugiperda, Spodoptera exigua and Cacyreus marshalli (geranium bronze).