Recent and Past Research
Project Statement:
Human life expectancy at birth has doubled over past 160 years byincreasing steadily 6 hours per day. This gain in vitality is due to unplanned prevention of diseases achieved by the improvement of the quality of life (water, nutrition, hygiene, sleep, etc.) that has increased the resilience of human organisms. Such increased resilience is certainly due to a change in human biochemistry.
We are developing methods for biomedical profiling, i.e.,the identification ofinborn weaknesses – fragile proteins - specific of each individual. Having identified the basic chemistry of cellular resilience, we expect to be able to provide the ubiquitous “chemistry of resilience” protecting fragile human proteinsagainst damage and thus improve prevention of all age related diseases assuringa healthy longevity.
Recent Research
Extreme anti-oxidant protection against ionizing radiation in bdelloid rotifers
We conclude that the great radioresistance of bdelloid rotifers is a consequence of an unusually effective system of anti-oxidant protection of cellular constituents, including those required for DSB repair, allowing bdelloids to recover and continue reproducing after doses of IR causing hundreds of DSBs per nucleus. Bdelloid rotifers therefore offer an advantageous system for investigation of enhanced anti-oxidant protection and its consequences in animal systems.
Stoichiometry of MutS and MutL at unrepaired mismatches in vivo suggests a mechanism of repair. Elez M, Radman M, Matic I. Source
Our results corroborate the hypothesis postulating that MutL accumulation assures the coordination of the MMR activities between the mismatch and the strand discrimination site.
Three Major Research Projects
This three tier project offers, at itsR & D stage,original science-based solutions to three major problems of humanity: healthy longevity, local food supplyand local energy supply. Mission and purpose of the first two projects is to profoundly change the public health by combining an original molecular diagnostics with a new treatment employing natural compounds, ofnutriceutical kind, that is both preventive and therapeutic.
Biology of robustness
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.
MedILS
The Mediterranean Institute for Life Sciences (MedILS) was conceived about 30 years ago by its founders Professors Miroslav Radman and Marija Alacevic as an international \'renaissance\' project inspired by the scientific culture of the most productive private institutes, such as the Rockefeller and Cold Spring Harbor Laboratory MedILS is an independent private, but non-profit international institution set up as a courageous scientific and societal experiment.
Past Research
RecA protein assures fidelity of DNA repair and genome stability in Deinococcus radiodurans.
Deinococcus radiodurans is one of the most radiation-resistant organisms known. It can repair hundreds of radiation-induced double-strand DNA breaks without loss of viability. Genome reassembly in heavily irradiated D. radiodurans is considered to be an error-free process since no genome rearrangements were detected after post-irradiation repair. Here, we describe for the first time conditions that frequently cause erroneous chromosomal assemblies.
Protein damage and death by radiation in Escherichia coli and Deinococcus radiodurans.
Deinococcus radiodurans is among a small number of bacterial species that are extremely resistant to ionizing radiation, UV light, toxic chemicals, and desiccation. We measured proteome oxidation (i.e., protein carbonylation, PC) in D. radiodurans as well as in standard and evolved resistant strains of Escherichia coli exposed to ionizing radiation or UVC light and found a consistent correlation with cell killing. The unique quantitative relationship between incurred PC and cell death holds over the entire range of killing for all tested bacteria and for both lethal agents, meaning that both bacterial species are equally sensitive to PC.
Unstructured hydrophilic sequences in prokaryotic proteomes correlate with dehydration tolerance and host association.
Here, we explore possible hallmarks of prokaryotic desiccation tolerance in their proteomes. The content of unstructured, low complexity (LC) regions was analyzed in a total of 460 bacterial and archaeal proteomes. It appears that species endowed with proteomes abundant in unstructured hydrophilic LC regions are desiccation-tolerant or sporulating bacteria, halophilic archaea and bacteria, or host-associated species.
Biological responses to DNA damage
DNA Repair Systems and Bacterial Evolution - Book Biological responses to DNA damage; page 11 - 19.
in the BOOK: SOS Hypothesis and the Emergence of Integrative Biology
A major discovery can often be recognized by the need to coin a new word (e.g., atom, radioactivity, antibiotic, apoptosis, etc). If the discovered entity or phenomenon does not have its cognate word in our vocabulary, it is surely a breakthrough. Coining the word SOS response (SOS system, SOS replication, SOS repair) to describe coordinated multiple inducible cellular responses to DNA damage resulting in induced mutagenesis and cell survival, was such a privilege (Radman 1974). This is a personal historical account of the intellectual circumstances that led to the birth of SOS hypothesis
