Antonella Folgori

Reithera Srl
Rome
Okairos

Viruses as vectors for novel genetic vaccines: challenges and success from mice to humans

Many viruses have been investigated for the development of genetic vaccines and the ideal ones must be endowed with many properties, such as the quality and the quantity of the immunological response induced against the encoded antigens, safety and production on a large scale basis. Viral based vaccines must also deal with the potential problem of the pre-existing anti-vector immunity. Several viral vaccine vectors have emerged to date, all of them having relative advantages and limits depending on the proposed application. Recent successes reflect diverse improvements such as development of new adenovirus serotypes and prime-boost regimes with different viral vectors to improve peak and longevity of adaptive immunity and induction of both humoral and cellular responses harnessing the ability of the different components of the immune system. We have developed new recombinant adenoviral vectors derived from chimpanzees and combined them with other viral vectors in prime-boost regimes that are now lead vaccine candidates against Ebola, HCV, RSV and Malaria based on their potent induction of T and B cell immunity in humans and on demonstration of their efficacy in preclinical animal models. Challenges and success of the translation from preclinical to clinical development of some of these vaccine candidates will be discussed.

Dònal O'Carroll

Monterotondo
Italy
EMBL

Non-coding solutions to developmental challenges.

The integrity of the genome transmitted to the next generation intrinsically relies on cells of the germ line. Processes that ensure germ cell development, genomic stability, and reproductive lifespan are essential for the long-term success of a species. We are interested in characterizing spermatogonial stem cell (SSC) populations that support fertility as well the regenerative capacity of the testis throughout adult life. In addition, we tackle fundamental questions regarding the mammalian male germ line and heredity from an RNA perspective. Specifically, our research explores the contribution of non-coding RNA (miRNA, piRNA and lncRNA) and RNA modification pathways within germ cell development as well as testicular homeostasis/regeneration. Our research objectives focus on the contribution of these emerging pathways on the underlying circuitry of self-renewal that underpins the SSC, as well as the coordination of the various cellular/differentiation processes of spermatogenesis.

Philipp Holliger

Cambridge
UK
MRC Laboratory of Molecular Biology

Reconstructing the RNA world

A critical event in the origin of life is thought to have been the emergence of an RNA molecule capable of self-replication as well as mutation, and hence evolution towards more efficient replication. While this primordial replicase appears to be have been lost in time, we can use synthetic biology to build modern-day “Doppelgangers” of the ancestral replicase to reconstruct and study life’s first genetic system. I will discuss our progress in the engineering and evolution of an RNA replicase and future challenges such as the integration of RNA self-replication within protocellular structures. Success in this area promises not only to revolutionize our understanding of abiogenesis but provide a fertile test-bed for models of prebiotic chemistry and early evolution.

Principles and applications of bacterial bioreporters for environmental monitoring.

The availability of chemical pollutants for organisms is a major parameter for understanding pollutant toxicity and for predicting biodegradation rates. One possibility to assess pollutant bioavailability is to use bacteria that are engineered to express an easily measurable protein (a so-called reporter protein) in response to contact to the pollutant. Here I will present some of the general design principles of engineering bioreporter strains, of different types of reporter bioassays and of quantitative interpretation of bioassay results in terms of pollutant bioavailability. A number of examples will be presented in which bioreporter bacteria were applied in field studies. Further application possibilities in microengineered systems are discussed.