Projects / Programmes
January 1, 2015
- December 31, 2018
| Code |
Science |
Field |
Subfield |
| 3.07.00 |
Medical sciences |
Metabolic and hormonal disorders |
|
| 1.02.00 |
Natural sciences and mathematics |
Physics |
|
| Code |
Science |
Field |
| B000 |
Biomedical sciences |
|
| Code |
Science |
Field |
| 3.02 |
Medical and Health Sciences |
Clinical medicine |
diabetes mellitus, cytosolic calcium, membrane potential, syncytium, confocal microscopy, complex network theory, scale-free systems, time series analysis, big data, advanced analytics, networks, in vitro tissue models
Researchers (12)
Organisations (1)
Abstract
Collective activity of cell populations presents a basic mode of operation in complex cell and tissue network rhythmicity and overall activity. Recently, technological advancements in biomarkers, microscopy optics, confocal scanning speed and novel, more sensitive detection systems allowed us to gather experimental data that could be assessed using tools of the theory of complex networks and thus better understand organizational and functional principles of living organs across various scales. Based on these preliminary results, communication among cells through cell-cell junctions shall be further upgraded with various forms of extracellular signaling by taking into account novel microfluidic approaches and Big Data analytical solutions. Such an analysis shall eventually make it possible to stream calcium kinetics in real-time during varying physiological and pharmacological stimulation regimes as well as in pathophysiological conditions. A combination of intracellular dynamics and microfluidic analysis will aid reconstruction of functional multicellular 3D models of tissues and yield understanding of physiology and pathophysiology in the context of a spatial organization and signaling landscape. Access to human tissue will enable a direct evaluation of the relevance of results obtained in animal models and is important from an evolutionary biology point of view as well as from the perspective of possible future clinical application. The results of our experiments and network analyses in the framework of the proposed research program shall thus be applied to help prevent, diagnose and treat important health issues. Initial emphasis shall be on studying pancreatic islets, endocrine organs delivering critically important hormones, such as insulin, to other cellular systems in a body. Impairment in insulin signaling results in diabetes mellitus, a public health threat that is expected to become one of the most prevailing human illnesses. In vitro 3D models of bioengineered complex tissues, especially the ones of non-transformed human origin, shall furthermore be constructed to facilitate pharmacological testing, environmental bio-compatibility and toxicology studies.
Significance for science
The tissue slice preparation was due to its complexity rarely used tool to study complex tissue function. We have recently established a novel preparation to study the endocrine function in pancreas, its endocrine part being vital for the control of the blood nutrients and its dysfunction being critical in severe diseases, like diabetes mellitus. Our preparation is the first, where the electrical activity, oscillations in the concentration of free cytosolic calcium and hormone (e.g. insulin) release and can be assessed in the intact tissue environment with a single cell resolution and where important cellular characteristics, like ion channels and metabolic activity can be assessed together with the secretory competence. We expect that the use of wild type, metabolically compromised rodent models, gene ablated animals and human samples will give us key information of the defects causing an endocrine disease, like diabetes mellitus and help us develop new methods prevention, diagnostics and treatment. We innovatively optimized approaches for the use of fluorescent markers of dynamic changes in cytosolic calcium concentration and membrane potential. Using an interdisciplinary approach we shall upgrade original experimental data with modern approaches of complex network theory, microfluidics, Big Data analysis and in vitro models of complex tissues.
Significance for the country
Endocrine disorders, like diabetes mellitus (DM), are widely spread in the developed world, where the Republic of Slovenia is no exception. Approximately 6% of the European population and more than 200 million people worldwide are afflicted by DM and due to its rising prevalence in developed as well as in developing countries this disease poses an ever greater public health problem (Pickup & Williams, 2003). The etiology of DM is only insufficiently understood but it is considered to be a polygenic and multifactorial disease that usually appears in middle age and is exacerbated by obesity. Due to epidemic dimensions of the disease and the way how it is diagnosed and treated at the moment it presents a serious threat for the public health system. Alternative and cost effective diagnosis and therapy of endocrine disease, like diabetes mellitus will be of significant advantage to unburden the public health system.
Most important scientific results
Annual report
2015,
2016,
2017,
final report
Most important socioeconomically and culturally relevant results
Annual report
2015,
2016,
2017,
final report
