Global food production from plants is at risk from insect pests. To protect their crops farmers spend a great deal of money on insecticides. For example, US farmers spent $1.2 billion in 2009 on insecticides for crop protection, which resulted in $22.9 billion of additional income due to crops saved from insect damage. However, the number of insecticides available to farmers is declining due to deregistration of some products for health and safety reasons, and due to the evolution of insects with insecticide resistance. It has been estimated there are over 500 insect pest species resistant to a total of over 300 insecticide compounds. Even the widely used bioinsecticide proteins from Bacillus thuringiensis (Cry1Ac, Cry1Ab, and Cry1F toxins) are now compromised by the documented evolution of insect resistance in many parts of the world. These B. thuringiensis proteins are used as Plant Incorporated Protectants (PIPs) in vast acreages of GMO crops that comprise a very large fraction of global agricultural production. The most effective strategy to keep them from becoming obsolete requires the incorporation of a stack of transgenes, encoding diverse protein-based insecticides with novel modes of action, to reduce the odds of insects evolving simultaneous resistance to all the expressed proteins. In summary, new, safe insecticides are needed to protect future food production, all the more so in view of the anticipated rise of global population to ~10 Billion by 2050. This proposal will work to enhance the function of a novel class of protein-based insecticides to an economically viable level, such that they can either be used as transgenes (PIPs), for large scale agriculture, or as biodegradable spray-on products to protect any crop from insect pests. The research focuses on a rate-limiting step in the delivery of these insecticidal proteins to their sites of action: the uptake of the ingested proteins from the insect gut across the insect gut wall. The project will screen large libraries of variable protein sequences for a short peptide that acts to enhance the uptake of attached cargo molecules from the insect gut into the insect hemolymph (~insect bloodstream). This peptide will be used with Vestarons portfolio of insecticidal proteins to enhance their insecticidal activity and make a more economically viable insecticidal product.