A COMPUTATIONAL APPROACH TO IDENTIFY TARGET RECEPTORS OF MARINE TOXINS IN THE HUMAN PROTEOME: POTENTIAL BIOTECHNOLOGICAL APPLICATIONS

• Autor(a) principal: Cabral, Inês Moutinho Ferreira Figueiredo
• Data de Publicação: 2022
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10362/136351
• topic: Glycera alba; Hediste diversicolor; Polychaeta; RNA-Seq; Venom; nteractome-directed analysis; Domínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e Tecnologias

The marine environment has a tremendous biodiversity, which implies an almost limitless source of bioreactives with potential biotechnological applications. Within these, proteinaceous toxins are highlighted as most evolved to interact with specific molecular targets. Toxins are part of complex cocktails, such as venoms, that are secreted for predation or defence. Recently, new drugs developed from marine natural products reached the market, like Prialt, a synthetic painkiller derived from a conotoxin. Altogether, marine invertebrates can be high-prized sources for novel bioreactives with biomedical applications, particularly the Polychaeta, due to their abundance and diversity albeit little explored. Glycera alba and Hediste diversicolor are two Polychaeta with distinct behaviours, but suspected to secrete toxins with different purposes. A comparative transcriptomic analysis between species and organs revealed distinct toxins and other bioreactives. Specifically, the venom apparatus of G. alba is localized in the proboscis and that neurotoxins and diffusing agents are secreted to overwhelm prey. On the other hand, H. diversicolor, an opportunistic forager, secretes fewer, less specific, toxins that are seemingly a defence measure against predators and pathogens. The analysis of protein-protein interactions between proteins predicted from the worms’ transcriptome and the human proteome allowed unravelling novel toxins and bioreactives with potential biomedical applications, from which two full-coding sequences from both species were isolated. Among these, are proteins from G. alba’s venom that can interfere with regulatory pathways of apoptosis, for instance involving FADD, BAD and FAIM. In turn, H. diversicolor yielded proteins that can regulate the human innate immune response. These results show that omics and bioinformatics can be a powerful tool for bioprospecting and drug discovery, enabling mining through complex transcriptomes even of organisms with reduced genomic annotation. They also show that interactome-directed analysis against the druggable human proteome can be a highly efficient alternative to the design of synthetic drugs.