Unraveling anuran host defense peptides (HDPs) and their biotechnological potential through a multi-omics computational approach

• Grant number: 24/21125-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2025
• End date: March 31, 2028
• Field of knowledge: Biological Sciences - Genetics - Animal Genetics
• Principal Investigator: Taran Grant
• Grantee: Esdras Matheus Gomes da Silva
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 18/15425-0 - A multi-disciplinary approach to the study of amphibian diversification: phase 2, AP.JP2

Abstract

Cutaneous exocrine granular glands of amphibians synthesize and secrete different compounds, including host defense peptides (HDPs). These HDPs are key molecules to defend against microorganisms, being especially widespread in anurans, and are potential biotechnological compounds for treating human infections caused by bacteria and fungi. The increasing number of antibiotic-resistant bacterial strains and fungal infections that are not treatable by conventional methods makes HDPs an important potential alternative for treatment of these infectious diseases. Furthermore, evidence of bioactive peptides found in the scientific literature shows that they have antiviral, antitumor, antidiabetic, and immunomodulatory properties, among others. Despite the importance of HDPs, there are currently no Linux command-line based computational tools available for predicting bioactive peptide that enables its integration into bioinformatic pipelines. Also, there is no updated database of anuran HPDs based on multi-omics data available until the present day. Moreover, the evolutionary origin of the different anuran HDPs has not yet been comprehensively elucidated. Despite the proven biotechnological importance of these peptides, few studies have explored their potential therapeutic targets through in silico approaches. Therefore, this project aims to apply multi-omics computational approaches to mine anura HDPs with potential therapeutic bioactivity, using publicly available data. The key goals of this project are to (1) develop an open-source computational Linux command-line based tool for the prediction, characterization and classification of peptides; (2) build a solid database of anuran HDPs; (3) investigate the evolutionary history of HDPs; and (4) infer potential therapeutic targets for anuran HPDs through a computational approach. The Linux command-line based computational tool will be able to characterize the physicochemical properties of peptides, categorize the antimicrobial peptides, and predict their bioactivity using a machine learning (ML) model. Subsequently, this computational tool will be applied to public multi-omics data to prospect anuran putative HDP sequences, which will be stored in an SQL database along with their metadata. Also, HDP homology will be inferred through an ML model developed in this project. And finally, the evolutionary history of anuran HDPs will be investigated using phylogenetic approaches, and virtual screening, molecular docking, molecular dynamics, and evaluation of potential protein therapeutic targets of anuran HPDs will also be investigated. Thus, we expect these results to expand knowledge regarding the evolutionary history of anuran HPDs and their potential biotechnological applications. Additionally, given the generalization power of the ML models, the computational tools we develop will enable the investigation of HPDs of other organisms.