Life’s robustness depends on the resilience of fertile organisms (the soma) that assure the long-term evolutionary success of the germ-line, i.e., species. In the framework of this project we explore the chemistry of two types of biological clocks: the species-specific somatic clock (robustness of the proteome and life span) and the universal germ-line clock (mutations and evolution). As model organisms, we explore the bacterium D. radiodurans and aquatic animals bdelloid rotifers as well as complex animals like tardigrades, all equally resistant to long-term desiccation and extreme doses of ionizing radiation.
We propose to lay the foundation of a new branch of biology – the biology of robustness – an investigative field that deals with mechanisms of biological robustness in rare species and applies them to standard species, including humans. By exploring the comparative molecular biology of highly robust species (such as the radiation and desiccation resistant bacterium Deinococcus radiodurans, and more complex eukaryotes such as Belloid Rotifers, Tardigrada and the immortal medusa Turritopsis nutricula) we anticipate to gain information that will allow us to manipulate macromolecular maintenance systems in cells and tissues of species that do not normally enjoy intrinsic robustness.
The specific aims of this project are:
(i) – to understand the molecular basis of biological robustness and how it mitigates “intrinsic aging”, i.e., decay of vital cellular functions that underlie the manifestations of aging, including age-related diseases.
(ii) – to purify and characterize a moiety(s) that we have discovered in specially prepared extracts of Deinococcus radiodurans (and other robust species, e.g., bdelloid rotifers, tardigrada and the immortal medusa Turritopsis nutricula) that confers proteome protection and radiation resistance to the proteomes of radiosensitive species. (iii) – to utilize the information gained to explore the slowing of ageing in mammals. To that end, new experimental systems and methods are proposed to explore the basis of life’s robustness and the chemistry of intrinsic ageing (hypothetically, the protein-based somatic clock).
(iv) – to explore the origins and causes of differences among individuals in human population facing aging, disease and death. Why, at high age, some individuals are robust, other fragile, while often unrelated to their robustness at young age? Are polymorphisms in proteins (or RNAs) “silent” at young age becoming phenotypic (“loud”) at advanced age? We wish to answer these questions by exploring the polymorphism of the susceptibility of different protein morphs to oxidation (carbonylation) that inactivates their correct functioning.