Projects / Programmes
January 1, 2004
- December 31, 2008
| Code |
Science |
Field |
Subfield |
| 3.03.00 |
Medical sciences |
Neurobiology |
|
| 4.06.00 |
Biotechnical sciences |
Biotechnology |
|
| 2.06.00 |
Engineering sciences and technologies |
Systems and cybernetics |
|
| Code |
Science |
Field |
| B470 |
Biomedical sciences |
Physiology |
cell physiology, cell engineering, adipocytes, pituitary cells, cell culture, clonal cells, insulin, secretion, prolactin, pituitary hormones, mitochondria, lactotrophs, exocytosis, endocytosis, calcium homeostasis, membrane capacitance, electrophysiology, confocal microscopy, immunohybridoma, cell fusion, biomedical instrumentation
Researchers (17)
Organisations (2)
Abstract
Chemical messengers and hormones are stored in cells in membrane bound vesicles. The contents of vesicles is released into the extracellular medium upon the fusion of the vesicle membrane with the plasma membrane, a process termed exocytosis. In many cells a stimulus is required to trigger exocytosis (regulated exocytosis), while in others exocytosis proceeds in a continuous fashion (constitutive exocytosis).
Practically all cells in human body perform a form of exocytosis. In some cells, such as neurons and endocrine cells, this process is particularly specialized. However, it is also present in adipocytes, cardiomiocytes, immune cells, photoreceptors, glial cells, plant cells and other cell types. Although exocytosis is an ubiquitous process of all eukaryotic cells, the molecular mechanisms regulating it are still unclear. In the last decade many proteins have been discovered to play a role in exocytosis, but the exact order and nature of their interactions underlying regulated exocytosis is unclear. On one side it has been hypothesized that a common molecular mechanism is essential for regulated exocytosis, but the interaction of other molecules with the essential set of molecules contribute to specific functional requirements. On the other side it has been proposed that regulated exocytosis is explained by a sequential molecular model, which states that all vesicles in a cell must undergo a sequence of events in order to fuse with plasma membrane.
To test these hypotheses, we study secretory activity in a number of model cell types, especially in pituitary cells from the anterior and intermediate lobes, which secrete prolactin, beta-endorphin and alpha-melanocyte stimulating hormone. These hormones are involved in the bodily response to stress, regulate the immune system, body temperature, body weight and other functions. In adition to this we also study the physiology of mitochondria, secretory activity of single astrocytes, adipocytes, skeletal muscle fibres and other cells.
Membrane fusion is an important process also in cell maturation, such as in the formation of skeletal muscle fibres. It also represents a key step in the production of hybrid cells used in the production of monoclonal antibodies and for the preparation of hybrid cells in immunotherapy of cancer. In these applications membranes of two adjacent cells fuse to form one cell-hybrid. In case of immunotherapy the fusion of dendritic cells with tumor cells enables the hybrid to retain properties of antigen presenting cells, but is presenting tumour antigens to other immune cells at the same time.
The aim of the "Cell Physiology" programme is therefore on one side to understand the fundamental properties of membrane fusion under physiological and pathological conditions, and on the other side to utilize this knowledge in developing hybrid cells and cell therapy related products.
Significance for science
We believe that the work conducted is significant on several different levels. First, it is interesting in its own right, providing new information about ubiquitous biological processes - exocytosis, vesicle traffic, cytosolic homeostasis of second messengers and metabolites - that at present are not well understood. Second, these are model systems for the study of ‘functional genomics and proteomics’. That is, for most complex biological processes involving the specific interactions of dozens of different genes and proteins, it is not possible to monitor the process in real-time in living organisms. For this one has to use single cells and multiple techniques used individually or simultaneously in combination to address questions related to the properties of functional modules contributing to the function of cells and organisms as a whole. Unitary exocytic events in lactotrophs, however, can be studied in this way. Understanding vesicle dynamics prior and after exocytosis can also be studied in single cells such as astrocytes, which are increasingly viewed as essential elements in information processing in the central nervous system in health and disease. The cytosolic events involving second messengers and metabolites that are associated with vesicle traffic are poorly understood and optical techniques in combination with fluorescent molecular probes provide an approach that promises new important directions to be opened in the future. In combination with tissue slices the function of single cells can be placed in the framework of a cell association. Finally, it seems reasonable to hope that this work, while not targeted to any particular disease, will be useful for helping to preserve and promote human health. Anterior pituitary hormones control important bodily functions including growth, development, reproduction, and responses to stress The release of hormones is controlled by factors released from innervating neurons (pars intermedia), or by circulating hypothalamic factors which via their interaction with specific surface membrane receptors and subsequent activation of intracellular signalling mechanisms control exocytosis. Thus a key to understanding neuroendocrine integration is to understand the mechanisms that control exocytosis. Astrocytes play important roles in the CNS function that have only recently been described, much of this has to be thanked to single cell studies in particular. Addressing the role of regulated exocytosis in cells playing a role in metabolic syndrome and diabetes, will potentially generate new vistas that will help formulate new paradigms for diagnostic/therapeutic approaches. Therefore, the conducted research does not only examine fundamental physiological/biophysical aspects of exocytosis, vesicle traffic, cytosolic signaling with second messengers and metabolites, but additionally reveals new aspects of physiological regulation of hormone and neurotransmitter release, vesicle traffic and cytosolic homeostasis in terms of conditions related to neurodegeneration, brain trauma, metabolic syndrome and diabetes.
Significance for the country
Cell Physiology represents an essential discipline for the development of new therapeutic and diagnostic methods in modern molecular medicine. Therefore, the strategy to support fundamental research and applied research at cellular level represents a strategy to deliver and support a much more rapid development of the whole society, including that in Slovenia. Fundamental research is essential for the education of future experts and also lay public. The latter needs to be educated in term of understanding the new developments in cell biology and molecular medicine. For example: the promissing new discoveries in stem cell research, subcellular physiology, cell engineering, cell transplantation, the biology and mechanisms of diseases, the mechanisms of treatment, and others need to be presented to the public. Furthermore, problem solving of universal problems at the highest possible methodological level is increasing the visibility, credibility and competence of the whole society. Expertise in the field of Cell Physiology, which has a tradition of several decades in Slovenia, promisses to support more rapid development for Slovenia, contributing significance for global efforts with the family of other nations.
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