Research Project Summary:
Novel drugs are urgently needed to combat the emergence of multiresistant pathogen species. Understanding and targeting antimicrobial resistance is one of the global health surveillance priorities. Our research group has a longstanding consolidated experience in the structure-functional characterization of human secreted RNases, a family of small cytotoxic proteins expressed by epithelial and blood cells upon infection. Host defence RNases belonging to a unique vertebrate specific gene family, show an unusual rapid evolution rate, a trait characteristic of innate immunity proteins, providing adaptation to an ever-changing pathogen exposed environment. Antimicrobial proteins have thus been selected through evolution to work as anti-infective agents against a wide variety of pathogen intruders.
Human secretory RNases are key players of the host immunity and contribute to maintain the body fluids' sterility. They are activated upon a diversity of cellular stress injuries and mediate signaling processes, classified therafter as alarmins. Interestingly, secreted RNases can shape the non-coding RNA population and participate thereby in the host innate immune response,
We are currently exploring both the immuno-modulation and inti-infective activities of human canonical RNases. Structural- functional analysis is applied in the design and engineering of new scaffolds to develop novel antibacterial and antiviral agents. In particular, we are aiming to target microbial resistance forms, such as biofilm communities and macrophage dwelling pathogens.
- Structural – functional characterization of human antimicrobial RNases.
- Patterns for host-pathogen recognition
- Patterns for pathogen RNA targeting
- Characterization of RNase activity on single stranded RNA viruses
- Design of novel antimicrobial agents