This talk is an activity from the FEBS Junior Section, an initiative set up by students and young researchers from some of the FEBS Constituent Societies. Each month a Junior Section from one of the participant Societies organizes an online event on either a research or a career topic. This June talk is the sixth event of the new 2023 talk series, has an academic focus, and is organised by the SIB Junior Section, the junior section of SIB, the Italian Society of Biochemistry and Molecular Biology.
Speaker: Prof. Loris Rizzello, University of Milan, Italy
Topic: “Towards an evolutionary-driven universal therapy against (intracellular) pathogens”
Time: 15 June, 18:00 (CET)
For more information, see the talk summary below and visit Prof. Loris Rizello's webpage.
Registration for the talk: https://us06web.zoom.us/meeting/register/tZYlce-qqTkoHNDDKreVb4cBQWPX135_518p
Infectious diseases for which vaccination and antimicrobial therapies have been particularly successful are caused by extracellular pathogens, namely bacteria spending a significant part of their lifecycle outside the cell. Conversely, vaccines and antibiotics against intracellular pathogens – bacteria evolved to invade, colonize and replicate within host cells – have been proved to be much more difficult to develop.(1) Humoral immunity, i.e., antibodies (Abs), can provide some (yet limited) protection also against intracellular pathogens.(2) However, the control and eradication of such parasites is still a preferential domain of cellular-based immunity. We propose here a research vision aiming to find a universal therapy to infectious diseases that will also counteract the development of drug resistance. We are specifically focused on eradicating human tuberculosis, one of the worst pandemics so far. To do this, we probe what are the molecular ‘bar-codes’ of infected cells, namely those specific membrane proteins that cells express upon infection. We use this information to reversely engineer a repertoire of super-selective polymeric nanoparticles – known as Polymersomes – that will carry ligands to recognise, bind, and selectively attack infected cells only, while leaving non-infected cells completely untouched. To precisely target infected cells only, we explored the concept of super selectivity where low-affinity multivalency replaces the established concept of high affinity
ligand-based targeting, which is at the base of off-targets effects. Such nanocarriers access the infected cells and locally deliver their payload, which is the core technology of the therapy. Such technology is inspired by the binding sequence of autolisins, proteins expressed by bacteriophages that specifically bind the wall of Mycobacteria species (the agent causing tuberculosis). We believe next efforts in nanoparticles-based drug delivery should take into account the option to re-design the way targeting efficiency has been conceived so far, and adopt the concept of low affinity multivalency binding.
- Griffiths, K. L. et al. Curr Opin Immunol 28, 58-63, (2014).
- Prados-Rosales, R. et al.. PLoS Pathog 13, e1006250, (2017).
The FEBS Junior Section
Want to join this platform for young European life scientists? Learn more about our initiative, check out the Room for the FEBS Junior Section and – if you do not have a junior section yet – read this post about how to set one up!