15. The Role of Mechanical Load in Treating Osteoporosis: Designing a Mechanical Osteoblast Stimulation Model to Investigate Curative Applications

Coordinator: Basdra Efthimia, Institution: National & Kapodistrian University of Athens

Osteoporosis constitutes the most frequent bone metabolic disease with severe social and economic consequences and high levels of morbidity and mortality. It is characterized by decreased bone mass, the disruption of the microarchitecture of the bone, reduced stamina and increased fracture frequency. Bone loss is due to excessive osteoclast (bone dissolving cells) activity and reduced osteoblast (bone-forming cells) activity. Osteoblast activity might be improved by mechanical stimulation of the osteoblasts. This action may be vitally important not only for preventing, but also for treating osteoporosis with systematic exercise and it should be scientifically validated. The current proposal seeks to study whether, and to what extent, the mechanical stimulation of osteoblasts (by applying pressure on the appropriate osteoblastic cells layers) modifies their behaviour as regards the secretion of various agents (cytokine, osseous, etc.) involved in osteogenesis. During the project’s second phase, an information booklet will be designed for broad distribution, which will contain explanations and instructions regarding the need for exercise, something this project will attempt to scientifically consolidate.

16. The Creation and Analysis of a New Genetic Model of Osteoporosis in Transgenic Mice Overexpressing the RANKL Cytokine

Coordinator: Douni Helen, Institution: Alexander Fleming Biomedical Sciences Research Center

Osteoporosis is a very serious illness, which primarily attacks women when they enter menopause. Its causes are primarily hormonal and low bone mass results from the imbalance between regenerative and bone destructive processes. When these processes function normally, they ensure bone health and renewal during the period of adulthood. Patients suffering from osteoporosis are administered drugs that boost the osteoblasts’ regenerative function, but, due to the serious side-effects, the illness is mainly treated by preventing bone fractures and proper nutrition. One reason for the limited range of medicines is the lack of proper animal models for trials. Using genetic engineering methods, the research team has already developed mice with an overproduction of a protein (the RANKL protein) that boosts the activity of the bone destroying cells. The proposal aims to further examine these mice in order to select the ones with the most severe symptoms of osteoporosis, which, however, may be cured after being treated with established drugs. Satisfying both these parameters will lead to the development of the first animal osteoporosis model, which will lead to the discovery of new specialized drugs.

17. The Genetic Differentiation of the Mitochondrial Genome and Its Co-evolution with the Nuclear Genome as a Speciation Mechanism in the Terrestrial Snails of Greece

Coordinator: Parmakelis Aristeidis, Institutions: National & Kapodistrian University of Athens / University of Patras

Mitochondria are factories producing cellular energy and are necessary for cell life, as well as, sometimes, for cell death. Mitochondria have their own DNA and it—like the rest of the genetic material—evolves. Indeed, because it is believed that its evolution occurs at a steady rate and without adaptive leaps, mitochondrial DNA is widely used to measure evolutionary time. For example, such measurements support humanity’s African origin. However, is the evolution of mtDNA truly neutral, or is it influenced by the evolution of the remaining nuclear genetic material? Co-evolution appears to be a plausible interpretation, since energy production requires the close interaction of nuclear and mitochondrial genes. Indeed, it has recently been suggested that the absence of such an effective interaction may lead to reproductive barriers and, therefore, to the appearance of new species. The project proposes to test the co-evolution hypothesis in a specific and precise manner. For this purpose, it will use populations from two types of snails to molecularly analyze one nuclear and one mitochondrial gene engaging in close interaction to produce energy. This research study will contribute to an understanding of complex evolutionary mechanisms, will provide important information regarding the mechanisms that lead to the appearance of new species, and will add new data regarding the adaptability of the cell’s bioenergy mechanisms.

18. What Lies Behind a Giant: the Case of the Skyros Lizard

Coordinator: Pafilis Panagiotis, Institutions: University of Michigan / National & Kapodistrian University of Athens / Imperial College

An interesting hypothesis advanced in the area of evolutionary ecology suggests that in isolated ecological systems, like those found on islands, small-sized animal species become gigantic, while large animals become dwarfed. Many consider this phenomenon constitutes a rule, resulting in the prevalence of the term “Island Rule”. One characteristic example is Indonesia’s Flores Island, where giant rodents and lizards have been documented, while dwarf elephant fossils have been discovered there, as well as, recently, the fossils of small-bodied humans (Homo floresiensis), who lived there 18,000 years ago. Despite many examples, the overall validity of this theory has recently been contested, and various explanations have been offered, as the case may be, for the phenomenon. The research proposal intends to test this “rule” on a small island off Skyros, where gigantism has been observed in a species of lizard. The aim is to discover the causes leading to gigantism through a comprehensive ecological analysis of this small biotope. The research study will provide new and interesting information regarding the important role of the ecological dynamic on the evolutionary process.

19. Development of a Diagnostic Drug for Alzheimer’s Disease

Coordinator: Pelekanou Maria, Institution: National Centre of Scientific Research "Demokritos"

Alzheimer’s disease is the most common form of dementia, affecting primarily the elderly and, due to the rise in life expectancy, expected to become the plague of the 21st century.  The disease takes hold gradually, usually within few years.  The first symptoms are vague and cannot be evaluated since, to date, no reliable, specific method exists for its early diagnosis.  Therefore, a timely and accurate diagnosis of Alzheimer’s disease is extremely sought-after, since a suitable pharmaceutical treatment may delay the advent of dementia.  The current proposal aims at the development of a diagnostic drug labelled with radioactive technetium-99m, designed to pass the blood-brain barrier and attach itself selectively to the amyloid plaques (the characteristic pathologοanatomical feature of Alzheimer's brain), allowing their imaging with scintigraphic camera.  The scientific workgroup has already carried out the in vitro biological evaluation of the candidate drug with satisfactory results.  The in vivo biological evaluation in normal and transgenic mice-models for Alzheimer's disease will follow to assess its diagnostic potential.

20. Automatic Detection of Heart Murmurs in Children’s Phonocardiograms and Development of Paediatric Auscultation Training Software

Coordinator: Stilianou Ioannis, Institutions: Foundation for Research &Technology (FORTH) / University of Crete

Cardiac auscultation is the first step in diagnosing each individual being examined, since it can reveal murmurs that indicate various heart valve disorders. However, in certain cases these murmurs are “functional”, in other words, they indicate nothing pathological, but are produced by other mechanisms. Separating functional from organic murmurs is vitally important during mass population examinations (e.g. schools, army), where the need is to identify patients with valve disorders, who, sooner or later, will develop heart disease. The advantages of auscultation are the examination’s simplicity, speed and minimal cost. However, it requires training and a certain expertise, which is not easy to acquire nowadays, since young doctors place greater reliance on new, more precise (but also more complicated and expensive) techniques. As a result, additional training in cardiac auscultation, particularly for children who are not sufficiently “cooperative”, in conjunction with the ability to automatically discern functional from organic murmurs is especially desirable. This is the exact purpose of the current proposal. Using the phonocardiograms of a large number of cardiology patients, which were analysed during the past years at the Hospital of Heraklion, the project will develop software, which will enable the automatic categorization of functional and pathological murmurs during school age, and, as a result, will ensure the correct diagnosis of valve diseases in the student population, providing the opportunity for respective, timely medical intervention. The system will be able to modify itself (to “educate” itself) as the original database expands.

21. The Genetic and Molecular Role of the AIF (Apoptosis Inducing Factor) Proteins in Activating the Innate Immune System of Plants

Coordinator: Tsitsigiannis Dimitrios, Institution: Agricultural University of Athens

Like all organisms, plants have their own “immune” system that allows them to deal with parasitic infections. The first line of defence is to identify the attacking microorganisms and produce substances that destroy them. The second line of defence is the programmed death of the cells affected; as a result, the spread of the attack is contained. In biology, the “beneficial” consequences of death are the rule rather than the exception. Approximately 50 billion cells die on a daily basis in our body, and this, among other things, protects us from serious diseases such as cancer, while programmed cell death is important for the proper functional state of our body. For example, for us to develop separate fingers, while still in the womb, the cells originally connecting them must die. Although animals and plants appear to have common programmed cell death mechanisms, the process has not been extensively studied in plants. The research proposal seeks to cast light on this process. It is based on his discovery of a group of genes in the model plant Arabidopsis thaliana that resemble the AIF gene of mammals, which is linked to a cell death pathway. The research study aims to investigate the role the plant AIF genes play in activating their defensive cell death.