Research | Human RNases involved in host defence

Human Ribonucleases involved in host defence

Our lab is working on the development of novel antibiotics based on the structure-functional knowledge of human secretory RNases.

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.

Our research involves the following projects:

- Design of novel antimicrobial agents against biofilms and macrophage intracellular bacteria
- Search for structural recognition patterns for pathogen RNA targeting

- Characterization of RNase activities on single- stranded RNA viruses
- Search for novel antibiotics to fight antimicrobial resistance

Transfer of Technology:

We are developing a novel anti-infective therapy to target antimicrobial resistance. BactRNAClean works by a novel strategy and combines high catalytic and antimicrobial activities. The construct has been successfully tested to inhibit bacterial resistance to colistin in Acinetobacter baumannii. The study has been co-financed by the European FEDER funds and the Secretaria d’Universitats i Recerca del Departament d’Empresa i Coneixement de la Generalitat de Catalunya (2019 LLAV 00002).

NETWORKS:

Global challenges research fund (GCRF) to promote an International Network on Antimicrobial Resistance. Birbeck- University of London (UCL).

Red Temática para el desarrollo de péptidos antivirales y antimicrobianos para cepas multiresistentes- 219 RT0573. RED BUDE Pav-am https://www.fis.unam.mx/~cgaray/Red/miembros_asociados.html

Search of novel antimicrobial peptides.

Human RNases involved in host defence

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