Several nanoparticles self-assemble from multiple copies of a limited number of building blocks, viruses being the archetypal example in biology. A majority of viruses have a highly ordered protein container (the capsid) that encloses and protects the viral genomic material from the environment. Understanding the structure of these capsids is fundamental to clarify how viruses work and possibly how they can be defeated and, to this purpose, a general classification scheme is needed. For viruses, the theory that identifies the relative position of the proteins was proposed by Caspar and Klug in the sixties and is still the current paradigm in the description of capsids. However, in the last decade scientists have started engineering many different self-assembling protein nanoparticles. The possible applications are manifold and innovative: from vectors for the delivery of genes or drugs to synthetic vaccines. The fast development of this research field poses new challenges for the structural analysis as, in general, synthetic nanoparticles do not fit into the Caspar and Klug’s framework: an original approach is needed to provide blueprints for the experimental determination of their structure. We focus on a de novo class of proteins, referred to as self-assembling protein nanoparticles (SAPNs). This is a family of nanoparticles that provide a versatile platform for synthetic vaccines against a broad range of diseases, including malaria, SARS, influenza and HIV. These nanoparticles self assemble from multiple copies of a polypeptide synthesized to have specific connectivity properties. The polypeptides bind to each other following precise local assembly rules forming groups of five or three polypeptides. To address the problem of elucidating the resulting assembled global structure, we use tools from graph theory. This approach unveils a hidden relation with fullerene geometries and enables a full classification of the high and low symmetry particles seen in experiments. First and foremost, this allows to determine the relative distance of the epitopes on the particle surface and tune the immunogenic effect of the vaccine.

The astonishingly long lives of plants and their regeneration capacity depend on the activity of plant stem cells. As in animals, stem cells reside in stem cell niches, which produce signals that regulate the balance between self-renewal and the generation of daughter cells that differentiate into new tissues. Plant stem cell niches are located within the meristems, which are organized structures that are responsible for most post-embryonic development. The continuous organ production that is characteristic of plant growth requires a robust regulatory network to keep the balance between pluripotent stem cells and differentiating progeny. Components of this network have now been elucidated and provide a unique opportunity for comparing strategies that were developed in the animal and plant kingdoms, which underlie the logic of stem cell behaviour.

Le cardiosfere sono state descritte per la prima volta da Messina et al. nel 2004, e rappresentano una sorta di microtessuto, di nicchia cellulare di progenitori cardiaci, che, in particolari condizioni di coltura, si genera spontaneamente in vitro a partire da cellule derivate da biopsia cardiaca. Negli ultimi anni la semplicità di questo metodo per l'isolamento di progenitori cellulari cardiaci e la loro espansione ex vivo sotto forma di sfere cellulari, ha dimostrato di essere una valida tecnologia per la terapia cellulare cardiaca, aprendo nuove opportunità per la rigenerazione del miocardio danneggiato per patologie acute (ischemia-infarto) o croniche (cardiomiopatie, insufficienza cardiaca di qualsiasi origine), anche se ancora molto resta da fare per migliorare l'applicabilità clinica. In questa conferenza a due voci, presenteremo le basi biologiche e le problematiche mediche relative alle cardiosfere e un primo modello matematico di tipo ibrido, nato dalla collaborazione tra medici, biotecnologi e matematici, costruito per descrivere alcune fasi del loro sviluppo. In questo modello, le cellule sono trattate a livello discreto, mentre la scala molecolare è descritta a livello continuo. La proliferazione e differenziazione delle cellule è trattata con processi stocastici guidati dai segnali chimici presenti. Spiegheremo in dettaglio la costruzione del modello, partendo dai dati biologici, e mostreremo alcune simulazioni numeriche, confrontandole con i risultati delle esperienze di laboratorio.

Euglenids are unicellular aquatic organisms capable of moving either by beating a flagellum or by executing dramatic shape changes. These are accomplished thanks to a complex structure underlying the plasma membrane, made of interlocking proteinaceous strips, microtubules, and motor proteins. We study the mechanisms by which the sliding of pellicle strips leads to shape control and locomotion, by means of both theory (through the mechanics of active surfaces and its coupling to computational fluid dynamics for the surrounding fluid) and experiments. Moreover, we implement them into a new concept of surfaces with programmable shape, obtained by assembling 3d-printed strips in a construct mimicking the biological template. We show that the subtle balance between constraints and flexibility leads to a wide variety of shapes that can be obtained with relatively simple controls. This suggests that euglenids exploit the passive resistance of body parts to reduce the complexity of controlling their shape.

Herpes zoster (HZ) is a painful disease caused by the reactivation of the varicella zoster virus(VZV) as cell mediated  immunity (CMI) goes down (e.g. with ageing). Hope-Simpson formulated (1965) the “exogenous boosting” hypothesis (EBH), according to which further infective exposures to VZV may boost CMI, resulting in a protective effect against HZ. Inclusion of the exogenous boosting hypothesis in VZV transmission models predicts a large transient wave in natural HZ incidence following mass varicella immunization. The fear of this HZ “boom” is a main responsible of the current stall of varicella vaccination in Europe. In this talk, I summarize recent results from a model incorporating a further noteworthy Hope-Simpson’s hypothesis, stating that each VZV reexposure increases CMI protection against HZ to levels higher than those conferred by previous ones. The “progressive immunity” model fits well available European HZ data, suggesting that the mechanism may be critical in shaping HZ patterns. The model suggests counter-intuitive implications of varicella immunization in relation to vaccine-related HZ and the epidemiology of HZ after varicella elimination. I conclude by discussing the challenges for future VZV research.