Development of a research centre for functional and genomic analysis of special cells at the University of Pécs (Q3923195): Difference between revisions
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Tasks to be implemented in the course of the project: Small-scale specialised cells play a critical role in many diseases, such as cancer stem cells or stem cells in the progression of cancer processes. Cytostatic therapy in surviving cancer cells is known to increase the expression of cancer stem cell transcription factors, which play a decisive role in the development of cytostatic resistance, metastases and reduced treatment effectiveness. Therefore, the development of cancer stem cells or cells similar to stem cells has a major impact on patients’ chances of survival. However, there are technical barriers to the study of these small numbers of special cells if the detection of small quantities requires a special set of devices. On the other hand, the relevant studies also require the availability of a dedicated system of equipment, the quality control of sterile conditions and transport routes. This justifies the need to set up a specialised research centre at the PTE to separate these small numbers of special cells and subsequently learn about their properties. The effect of mitochondrim on the expression of stem cell markers. The high purity separation of cancer stem cells or stem cell-like cells is performed by the Flow-citometer, cell sorter system, the metabolic studies are performed with Seahorse and the analysis of isolated small amounts of existing cells is performed under sterile conditions (e.g. examination of changes in long-term mitochondrial function) using the fluorescent microscope (ImageXpress Micro XLS High Content Screening system) connected to the CO2 thermostat. Microparticles and plasma membrane fragments released from cancer cells as a result of cytostatic therapy are associated with cell death and cell transformations, which provide new information on the cell death effects of cytostatics. These studies reveal the role of mitochondium in reprogramming cytostatic-induced cancer stem cells or stem cell-like cells and contribute to understanding mitochondrial regulation possibilities. The effect of changes in mitochondrium function on changes in the expression profile of cancer stem cells or stem cells. Reproducible RNA and DNA isolation from modest cells are performed by the AS4500 Maxwell RSC System DNA RNA isolation automatic system and the quality analysis of RNA is performed using the Agilent 2100 Bioanalyser special equipment for the mRNA profile. The mRNA profile is measured either by the Illumina MiniSeq system or by the Affimetrix array system, the validation of results is the effect of the reprogramming of cancer cells into stem cells. In addition, these improvements make it possible to analyse changes in expression profiles, which can provide information on how to remove the expression profile typical of cancer stem cells. In addition, we will investigate the development of mutations induced by cytostatic therapy, a process that is of paramount importance in tumor and transmission formation, which is tested with the 384 hole qPCR system. Based on these data, we can determine mitochondrial transmission paths that lead to mitochondial regulation of gene expressions. The possibility of controlling mitochondrial states and membrane potential with synthetic small molecules. Several publications have shown that mitochondria also play an important role in maintaining the stem cell character of cancer cells, thus raising the possibility that changing the mitochondrial membrane potential through molecules directed into mitochondrium could change the stem cell character of cancer cells. In our previous studies, it has already been indicated that molecules directed into mitochondrium have a positive effect on cancer cells, namely shifting signalling processes towards cell death. These data indicate the potential role of mitochondrium-directed molecules in the elimination of cytostatic resistance, such as phosphonium salts associated with N-oxylpyrrolidine. In this area, we have research experience that will enable us to successfully attempt the synthesis of new types of conjugates containing both structural elements. These studies may show the chemical potential through which cancer cells can be destroyed before the cancer develops into stem cells. Further development of synthetic chemical potential, synthesis of molecules directed into mitochondrium. The target compounds that cause the destabilisation of mitochondrium include several functionalised carboxylic acidamides, lactams, aldehyde, small molar mass kiral compounds, chiral building blocks, the synthesis of which can be achieved in advance. Tapa acquired in the field of the synthesis of heterocyclic compounds for decades (English) | |||||||||||||||
| Property / summary: Tasks to be implemented in the course of the project: Small-scale specialised cells play a critical role in many diseases, such as cancer stem cells or stem cells in the progression of cancer processes. Cytostatic therapy in surviving cancer cells is known to increase the expression of cancer stem cell transcription factors, which play a decisive role in the development of cytostatic resistance, metastases and reduced treatment effectiveness. Therefore, the development of cancer stem cells or cells similar to stem cells has a major impact on patients’ chances of survival. However, there are technical barriers to the study of these small numbers of special cells if the detection of small quantities requires a special set of devices. On the other hand, the relevant studies also require the availability of a dedicated system of equipment, the quality control of sterile conditions and transport routes. This justifies the need to set up a specialised research centre at the PTE to separate these small numbers of special cells and subsequently learn about their properties. The effect of mitochondrim on the expression of stem cell markers. The high purity separation of cancer stem cells or stem cell-like cells is performed by the Flow-citometer, cell sorter system, the metabolic studies are performed with Seahorse and the analysis of isolated small amounts of existing cells is performed under sterile conditions (e.g. examination of changes in long-term mitochondrial function) using the fluorescent microscope (ImageXpress Micro XLS High Content Screening system) connected to the CO2 thermostat. Microparticles and plasma membrane fragments released from cancer cells as a result of cytostatic therapy are associated with cell death and cell transformations, which provide new information on the cell death effects of cytostatics. These studies reveal the role of mitochondium in reprogramming cytostatic-induced cancer stem cells or stem cell-like cells and contribute to understanding mitochondrial regulation possibilities. The effect of changes in mitochondrium function on changes in the expression profile of cancer stem cells or stem cells. Reproducible RNA and DNA isolation from modest cells are performed by the AS4500 Maxwell RSC System DNA RNA isolation automatic system and the quality analysis of RNA is performed using the Agilent 2100 Bioanalyser special equipment for the mRNA profile. The mRNA profile is measured either by the Illumina MiniSeq system or by the Affimetrix array system, the validation of results is the effect of the reprogramming of cancer cells into stem cells. In addition, these improvements make it possible to analyse changes in expression profiles, which can provide information on how to remove the expression profile typical of cancer stem cells. In addition, we will investigate the development of mutations induced by cytostatic therapy, a process that is of paramount importance in tumor and transmission formation, which is tested with the 384 hole qPCR system. Based on these data, we can determine mitochondrial transmission paths that lead to mitochondial regulation of gene expressions. The possibility of controlling mitochondrial states and membrane potential with synthetic small molecules. Several publications have shown that mitochondria also play an important role in maintaining the stem cell character of cancer cells, thus raising the possibility that changing the mitochondrial membrane potential through molecules directed into mitochondrium could change the stem cell character of cancer cells. In our previous studies, it has already been indicated that molecules directed into mitochondrium have a positive effect on cancer cells, namely shifting signalling processes towards cell death. These data indicate the potential role of mitochondrium-directed molecules in the elimination of cytostatic resistance, such as phosphonium salts associated with N-oxylpyrrolidine. In this area, we have research experience that will enable us to successfully attempt the synthesis of new types of conjugates containing both structural elements. These studies may show the chemical potential through which cancer cells can be destroyed before the cancer develops into stem cells. Further development of synthetic chemical potential, synthesis of molecules directed into mitochondrium. The target compounds that cause the destabilisation of mitochondrium include several functionalised carboxylic acidamides, lactams, aldehyde, small molar mass kiral compounds, chiral building blocks, the synthesis of which can be achieved in advance. Tapa acquired in the field of the synthesis of heterocyclic compounds for decades (English) / rank | |||||||||||||||
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| Property / summary: Tasks to be implemented in the course of the project: Small-scale specialised cells play a critical role in many diseases, such as cancer stem cells or stem cells in the progression of cancer processes. Cytostatic therapy in surviving cancer cells is known to increase the expression of cancer stem cell transcription factors, which play a decisive role in the development of cytostatic resistance, metastases and reduced treatment effectiveness. Therefore, the development of cancer stem cells or cells similar to stem cells has a major impact on patients’ chances of survival. However, there are technical barriers to the study of these small numbers of special cells if the detection of small quantities requires a special set of devices. On the other hand, the relevant studies also require the availability of a dedicated system of equipment, the quality control of sterile conditions and transport routes. This justifies the need to set up a specialised research centre at the PTE to separate these small numbers of special cells and subsequently learn about their properties. The effect of mitochondrim on the expression of stem cell markers. The high purity separation of cancer stem cells or stem cell-like cells is performed by the Flow-citometer, cell sorter system, the metabolic studies are performed with Seahorse and the analysis of isolated small amounts of existing cells is performed under sterile conditions (e.g. examination of changes in long-term mitochondrial function) using the fluorescent microscope (ImageXpress Micro XLS High Content Screening system) connected to the CO2 thermostat. Microparticles and plasma membrane fragments released from cancer cells as a result of cytostatic therapy are associated with cell death and cell transformations, which provide new information on the cell death effects of cytostatics. These studies reveal the role of mitochondium in reprogramming cytostatic-induced cancer stem cells or stem cell-like cells and contribute to understanding mitochondrial regulation possibilities. The effect of changes in mitochondrium function on changes in the expression profile of cancer stem cells or stem cells. Reproducible RNA and DNA isolation from modest cells are performed by the AS4500 Maxwell RSC System DNA RNA isolation automatic system and the quality analysis of RNA is performed using the Agilent 2100 Bioanalyser special equipment for the mRNA profile. The mRNA profile is measured either by the Illumina MiniSeq system or by the Affimetrix array system, the validation of results is the effect of the reprogramming of cancer cells into stem cells. In addition, these improvements make it possible to analyse changes in expression profiles, which can provide information on how to remove the expression profile typical of cancer stem cells. In addition, we will investigate the development of mutations induced by cytostatic therapy, a process that is of paramount importance in tumor and transmission formation, which is tested with the 384 hole qPCR system. Based on these data, we can determine mitochondrial transmission paths that lead to mitochondial regulation of gene expressions. The possibility of controlling mitochondrial states and membrane potential with synthetic small molecules. Several publications have shown that mitochondria also play an important role in maintaining the stem cell character of cancer cells, thus raising the possibility that changing the mitochondrial membrane potential through molecules directed into mitochondrium could change the stem cell character of cancer cells. In our previous studies, it has already been indicated that molecules directed into mitochondrium have a positive effect on cancer cells, namely shifting signalling processes towards cell death. These data indicate the potential role of mitochondrium-directed molecules in the elimination of cytostatic resistance, such as phosphonium salts associated with N-oxylpyrrolidine. In this area, we have research experience that will enable us to successfully attempt the synthesis of new types of conjugates containing both structural elements. These studies may show the chemical potential through which cancer cells can be destroyed before the cancer develops into stem cells. Further development of synthetic chemical potential, synthesis of molecules directed into mitochondrium. The target compounds that cause the destabilisation of mitochondrium include several functionalised carboxylic acidamides, lactams, aldehyde, small molar mass kiral compounds, chiral building blocks, the synthesis of which can be achieved in advance. Tapa acquired in the field of the synthesis of heterocyclic compounds for decades (English) / qualifier | |||||||||||||||
point in time: 8 February 2022
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Revision as of 17:46, 8 February 2022
Project Q3923195 in Hungary
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | Development of a research centre for functional and genomic analysis of special cells at the University of Pécs |
Project Q3923195 in Hungary |
Statements
737,586,000 forint
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2,016,283.972 Euro
0.0027336256 Euro
15 December 2021
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737,586,000.0 forint
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100.0 percent
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1 March 2017
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22 September 2020
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PÉCSI TUDOMÁNYEGYETEM
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46°4'35.72"N, 18°13'40.94"E
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A projekt során megvalósítani kívánt feladatok: A kis mennyiségben előforduló speciális sejtek sok betegségben játszanak kritikus szerepet, mint a rákos folyamatok progressziójában a rák őssejtek, vagy őssejthez hasonló sejtek. Az ismert, hogy a citosztatikus kezelés a túlélő rák sejtekben megnöveli a rák őssejtek transzkripciós faktorainak a kifejeződését, amelyek meghatározó szerepet játszanak a citosztatikus rezisztencia kialakulásában, metasztázisok képződésében és a kezelés hatékonyságának lecsökkenésében. Ezért a rák őssejtek, vagy őssejthez hasonló sejtek kialakulása nagy hatással van a betegek túlélési esélyeire. Ugyanakkor e kis számban előforduló speciális sejtek tanulmányozása technikai akadályokba ütközik, amennyiben a kis mennyiségek kimutatása speciális eszközparkot igényel. Másfelől, a vonatkozó vizsgálatok azt is megkövetelik, hogy dedikált eszközrendszeren, a steril körülmények és szállítási útvonalak minőségellenőrzött biztosítása is rendelkezésre álljon. Ez indokolja annak a szükségességét, hogy egy olyan specializált kutatóközpont létrehozására van szükség a PTE-n, amely ezeknek a kis számban előforduló speciális sejteknek az elválasztását, és ezt követően tulajdonságaik megismerését lehetővé teszi. A mitokondrim állapotának a hatása az őssejt markerek kifejeződésére. A rák őssejtek, vagy őssejthez hasonló sejtek nagytisztaságú elválasztása a Flow-citométer, sejt szorter rendszerrel történik, a metabolikus vizsgálatokat a Seahorse készülékkel hajtjuk végre és az izolált kis mennyiségben meglévő sejtek analízisét steril körülmények közt (pl. hosszú távú mitokondriális funkció változásának vizsgálata) a CO2 termosztáthoz kapcsolt fluoreszcens mikroszkóp (ImageXpress Micro XLS High Content Screening rendszer)-el végezzük. A citostatikus kezelés hatására a rák sejtekből kiszabaduló mikropartikulumok és plazma membrán fragmentumok összefüggésben vannak a sejthalállal és a sejtek transzformációival mely adatok alapján új információt kapunk a citosztatikumok sejthalált okozó hatásairól. Ezek a vizsgálatok feltárják a mitokondium szerepét a citosztatikum indukálta rák őssejtek, vagy őssejthez hasonló sejtek reprogramozásáról és hozzá járulnak a mitokondriális regulációs lehetőségek megismeréséhez. A mitokondrium funkció változásának a hatása a rák őssejtek, vagy őssejthez hasonló sejtek expressziós profiljának a változásához. A szerény mennyiségben lévő sejtekből reprodukálható RNS és DNS izolálás az AS4500 Maxwell RSC System DNS RNS izoláló automata rendszerrel történik és RNS minőség analízisét az Agilent 2100 Bioanalyzer speciális berendezéssel végezzük el a mRNS profilt. Az mRNS profilt vagy az Illumina MiniSeq rendszerrrel mérjük meg, vagy az Affimetrix array rendszerével, az eredmények validálása a membrán rendszer állapotának hatása a rák sejtek őssejtté történő reprogramozásának. Ezen felül ezek a fejlesztések teszik lehetővé az expressziós profilok változásának analízisét, amellyel információt kaphatunk arra vonatkozóan, hogyan tudjuk eltüntetni a rákos őssejtekre jellemző expressziós profilt. Továbbá, vizsgálni fogjuk a citosztatikus kezelés által indukált mutációk kialakulását, amely folyamat kiemelt fontosságú a tumor és áttételképződésben, ennek vizsgálata a 384 lyukú qPCR rendszerrel történik. Ezen adatok alapján határozhatjuk meg a mitokondriális jelátviteli utakat melyek elvezetnek a génexpressziók mitokondiális szabályozásához. A mitokondriális állapotok és a membrán potenciál szabályozásának lehetősége szintetikus kismolekulákkal. Számos publikáció igazolta, hogy mitokondriumok is fontos szerepet játszanak a rák sejtek őssejt jellegének („stemness”) fenntartásában, így felvetődik az a lehetőség, hogy a mitokondriális membrán potenciál megváltoztatása a mitokondriumba irányított molekulákon keresztül megváltoztathatná a ráksejtek őssejt jellegét. Korábban végzett vizsgálatainkban már jelezték, hogy a mitokondriumba irányított molekulák kedvezően hatnak a rák sejtekre, nevezetesen a sejthalál irányába tolják el a jelátviteli folyamatokat. Ezek az adatok jelzik a mitokondriumba irányított molekuláknak a lehetséges szerepét a citosztatikum rezisztencia megszüntetésében, így az N-oxil-pirrolidin-hoz kapcsolt foszfóniumsók esetében. Ezen a területen rendelkezünk olyan kutatási tapasztalatokkal, amelyek birtokában sikerrel kísérelhetjük meg az új típusú, minkét szerkezeti elemet tartalmazó konjugátumok szintézisét. Ezen vizsgálatok kimutathatják azokat a kémiai lehetőségeket, melyeken keresztül a rák sejtek elpusztíthatók a rák őssejté alakulása előtt. A szintetikus kémiai lehetőségek tovább fejlesztése, mitokondriumba irányított molekulák szintézise. A mitokondrium destabilizációját okozó célvegyületek között több funkcionalizált karbonsavamid, laktám, aldehid, kis moláris tömegű királis vegyület, királis építőelem szerepel, amelyek szintézise az előkísérletek ismeretében megvalósítható. A munkacsoport több évtizedes, heterociklusos vegyületek szintézise területén szerzett tapa (Hungarian)
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Tasks to be implemented in the course of the project: Small-scale specialised cells play a critical role in many diseases, such as cancer stem cells or stem cells in the progression of cancer processes. Cytostatic therapy in surviving cancer cells is known to increase the expression of cancer stem cell transcription factors, which play a decisive role in the development of cytostatic resistance, metastases and reduced treatment effectiveness. Therefore, the development of cancer stem cells or cells similar to stem cells has a major impact on patients’ chances of survival. However, there are technical barriers to the study of these small numbers of special cells if the detection of small quantities requires a special set of devices. On the other hand, the relevant studies also require the availability of a dedicated system of equipment, the quality control of sterile conditions and transport routes. This justifies the need to set up a specialised research centre at the PTE to separate these small numbers of special cells and subsequently learn about their properties. The effect of mitochondrim on the expression of stem cell markers. The high purity separation of cancer stem cells or stem cell-like cells is performed by the Flow-citometer, cell sorter system, the metabolic studies are performed with Seahorse and the analysis of isolated small amounts of existing cells is performed under sterile conditions (e.g. examination of changes in long-term mitochondrial function) using the fluorescent microscope (ImageXpress Micro XLS High Content Screening system) connected to the CO2 thermostat. Microparticles and plasma membrane fragments released from cancer cells as a result of cytostatic therapy are associated with cell death and cell transformations, which provide new information on the cell death effects of cytostatics. These studies reveal the role of mitochondium in reprogramming cytostatic-induced cancer stem cells or stem cell-like cells and contribute to understanding mitochondrial regulation possibilities. The effect of changes in mitochondrium function on changes in the expression profile of cancer stem cells or stem cells. Reproducible RNA and DNA isolation from modest cells are performed by the AS4500 Maxwell RSC System DNA RNA isolation automatic system and the quality analysis of RNA is performed using the Agilent 2100 Bioanalyser special equipment for the mRNA profile. The mRNA profile is measured either by the Illumina MiniSeq system or by the Affimetrix array system, the validation of results is the effect of the reprogramming of cancer cells into stem cells. In addition, these improvements make it possible to analyse changes in expression profiles, which can provide information on how to remove the expression profile typical of cancer stem cells. In addition, we will investigate the development of mutations induced by cytostatic therapy, a process that is of paramount importance in tumor and transmission formation, which is tested with the 384 hole qPCR system. Based on these data, we can determine mitochondrial transmission paths that lead to mitochondial regulation of gene expressions. The possibility of controlling mitochondrial states and membrane potential with synthetic small molecules. Several publications have shown that mitochondria also play an important role in maintaining the stem cell character of cancer cells, thus raising the possibility that changing the mitochondrial membrane potential through molecules directed into mitochondrium could change the stem cell character of cancer cells. In our previous studies, it has already been indicated that molecules directed into mitochondrium have a positive effect on cancer cells, namely shifting signalling processes towards cell death. These data indicate the potential role of mitochondrium-directed molecules in the elimination of cytostatic resistance, such as phosphonium salts associated with N-oxylpyrrolidine. In this area, we have research experience that will enable us to successfully attempt the synthesis of new types of conjugates containing both structural elements. These studies may show the chemical potential through which cancer cells can be destroyed before the cancer develops into stem cells. Further development of synthetic chemical potential, synthesis of molecules directed into mitochondrium. The target compounds that cause the destabilisation of mitochondrium include several functionalised carboxylic acidamides, lactams, aldehyde, small molar mass kiral compounds, chiral building blocks, the synthesis of which can be achieved in advance. Tapa acquired in the field of the synthesis of heterocyclic compounds for decades (English)
8 February 2022
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Pécs, Baranya
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Identifiers
GINOP-2.3.3-15-2016-00025
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