REFRACT research objective is to address major challenges in the TRP field: to benchmark and improve the existing TRP detection methods and to improve our understanding of TRP functional mechanisms and evolution.

This aim will be achieved by the following steps:

• Benchmarking existing methods and defining their use-cases
• Coordinating steps to analyze analyze TRP roles in biological pathways and organism evolution
• Providing a detailed description of their mechanism of function
• Building and characterizing a commonly accepted TRP classification from sequence and structure

TRP regions are considerably diverse, ranging from single amino acid homorepeats detectable by their lack of sequence complexity, to cryptic repeats of up to 40 residues per unit and even entire domains. The typical TRP sequences fold into a modular protein structure composed by the repetition of the same structural unit. Overall, such sequences are ubiquitous in genomes, and overrepresented in complex organisms, e.g. being present in almost every third human protein. TRPs found their perfect functional niche in the biological pathways that require fast evolution, such as host-pathogen interactions, and played an essential role in the evolution of eukaryotes, compensating their lower mutation rates. In addition, numerous studies over the last decade have related TRPs to human diseases and emerging infection threats, confirming the essentiality of their function.