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Projects / Programmes source: ARIS

Lysosomal fusion

Research activity

Code Science Field Subfield
3.03.00  Medical sciences  Neurobiology   

Code Science Field
B470  Biomedical sciences  Physiology 
Keywords
lysosomal fusion, quantitative 3D colocalization, confocal microscopy, hybridoma cells
Evaluation (rules)
source: COBISS
Researchers (5)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  23345  PhD Mateja Gabrijel  Pharmacy  Researcher  2007 - 2009  47 
2.  15666  PhD Marko Kreft  Neurobiology  Researcher  2007 - 2009  684 
3.  21390  PhD Maja Potokar  Medical sciences  Researcher  2007 - 2009  161 
4.  31572  PhD Saša Trkov Bobnar  Microbiology and immunology  Researcher  2009  56 
5.  03702  PhD Robert Zorec  Neurobiology  Head  2007 - 2009  802 
Organisations (1)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0381  University of Ljubljana, Faculty of Medicine  Ljubljana  1627066  48,195 
Abstract
Lysosomes are subcellular organelles playing a myriad of cell functions, including antigen presentation to the immune system. It is believed that in malignant cells the latter process is impaired, since cancer cells are »invisible« for the immune system surveillance. How to reestablish the recognition of cell tumor antigens by the immune system is a key challenge in the development of new treatments to cure various cancer diseases. The aim of the proposed project is to study the properties of lysosomal fusion arising from heterologous cells. This knowledge is instrumental for the development and production of efficient cell based cancer vaccines. Dendritic cell based vaccines are considered as a promising strategy to stimulate host immunity to recognize and eliminate malignant cells. The most promising design of dendritic cell based vaccines are hybridomas, that are produced by the fusion of dendritic and tumor cells. The potential advantage that distinguishes this approach from other dendritic cell strategies is that hybridomas present known and unknown tumor antigens on their surface in context with costimulatory molecules and MHC molecules class II and I that arise from dendritic cells. Antigen presentation in such a way results in the induction of a correspondingly balanced cytotoxic and T-helper cell responses. The activation of T helper cells is crucial for effective and durable antitumor immunity. Clinical trials have demonstrated that hybridomas are able to stimulate tumor specific immunity, however only a subset of patients experienced disease regression or stabilization. There are many reasons underlying the low efficiency of hybridoma tumor vaccines. The immunogenicity of hybridoma tumor vaccine depends on the amount of hybridoma cells and on their quality: i.e. the tumor antigens represented on the surface of hybridomas. However, to understand the latter process we critically require an insight into the role of lysosomes in hybridoma cell production. If in a hybridoma cell, generated by fusion of two donor cells, is supposed to present antigens of both cells on the common cell hybridoma surface, then fusion of lysosomes is anticipated, but has not been determined yet. Therefore, the aim of the proposed project is to establish whether in hybridoma cells, consisting of heterologous cells, such as dendritic and tumour cells, lysosomal fusion occurs. To this end we will introduce approaches to label, monitor and analyse single lysosomes by laser confocal microscopy and quantitative image analysis. We strongly believe that this study, if funded, will provide a completely new insight into the understanding of the grossly understudied lysosomal fusion arising from heterologous cells, crucial for the development of cell based anti-tumor vaccines.
Significance for science
Cancer is the second leading cause of death in most Western countries in the second half of the 20th century, being exceeded only by deaths from heart disease. However, many forms of cancer can be cured by traditional methods: surgery, chemotherapy and radiotherapy. However, pften it is impossible to eradicate every single one of them. If even a few cancerous cells remain, they can proliferate, which causes a remission of the disease. The improved understanding of cellular biology has led to a number of new, adjuvant treatments for cancer. One of the most promising is cellular immunotherapy. The main goal of the basic research in cellular immunotherapy is the development of methods to stimulate the body's immune response in order to defend itself against malignant tumors. Therefore, it is of key importance to exactly understand the dynamic and basic interactions of organelles involved in antigen presenting pathway of immune cells. The overall goal of this basic research was to achieve the fundamental knowledge that can be translated into clinical applications.
Significance for the country
Cancer is one of the major public health issues and challenges in Europe as well as in Slovenia. It affects the entire population as it has a significant impact on the quality of life of patients and their family members, while the extremely high healthcare expenditures related to this represents a burden for the public health care. Therefore, early detection and effective treatment of cancer are of utmost importance. The added value of this project is expressed by introducing innovative procedures based on own research results obtained in human cell treatment: with the objective of providing new effective treatment of cancer. The project is very important for Slovenia’s progress also in terms of developing research staff in the biotechnology branch, which by implementing high value-added projects contributes to the prosperity of the Slovenian society.
Most important scientific results Annual report 2008, final report, complete report on dLib.si
Most important socioeconomically and culturally relevant results Annual report 2008, final report, complete report on dLib.si
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