Cookies help us deliver our services. By using our services, you agree to our use of cookies. More information

Difference between revisions of "User talk:Tindle Lisa/My sandbox Support page v2"

From Bioblast
 
(16 intermediate revisions by 2 users not shown)
Line 1: Line 1:
{{Template:OROBOROS header page name}}
{{Template:OROBOROS support page name}}


<big><big>'''"A reprogramming-based strategy for drug repositioning in patients with mitochondrial DNA-associated Leigh syndrome (MILS)"'''</big></big>
:::::::::::: <big>''Currently Asked Questions - »'''[[O2k-Open Support alert]]'''« </big>  


<!--        TODAY'S FEATURED CONTENT        -->
{| role="presentation" id="mp-upper" style="width: 100%; margin-top:4px; border-spacing: 0px;"
<!--        1ST BOX | CURRENT WEEK AGENDA - LEFT        -->
| id="mp-left" class="MainPageBG" style="width:75%; border:1px solid #99b4ed; padding:0; background:#f0f5ff; vertical-align:top; color:#000;"|
<div id="mp-tfa-h2" style="margin:0.5em; background:#2856ba; font-family:inherit; font-size:120%; font-weight:bold; border:1px solid #a3bfb1; color:#ffffff; padding:0.2em 0.4em;"></div>
<div id="mp-tfa" style="padding:0.1em 0.6em;">
__TOC__
== O2k-Open Support resources ==
[[File:Expand.png|right|45px |Click to expand or collaps]]
<div class="toccolours mw-collapsible mw-collapsed">
'''Startup information'''


__TOC__
<div class="mw-collapsible-content">
 
 
:::: Each O2k-Package includes a remote installation and startup support session with an Oroboros expert, which can be scheduled during any time within the O2k-Warranty period (max. 2 years)
:::::» '''[https://www.oroboros.at/index.php/support-session-request-form/ Register for your session]'''
 
:::::» [[Installation and startup support session self-study material]]
:::: Upon special request and subject to an additional fee, Oroboros Instruments offers a start-up visit by a scientific application specialist.
:::::» [[O2k on-site training]]


:::: Additional reading
:::::» [[MiPNet20.04 O2k-checklist| Getting started with an O2k-experiment]]
:::::» O2k-Workshop self-study material: [https://wiki.oroboros.at/index.php/Virtual_O2k-Workshop_self-study_material#O2k-Basic O2k-Basic]
</div>
</div>


== "Project Name": "Funding Scheme" ==
[[File:Expand.png|right|45px |Click to expand or collaps]]
::::*  EJP RD JTC 2020: "PRE-CLINICAL RESEARCH TO DEVELOP EFFECTIVE THERAPIES FOR RARE DISEASES” - Project EJPRD20-010
<div class="toccolours mw-collapsible mw-collapsed">
::::* '''Duration''': 36 months
'''Quality control'''
::::* '''Start''': 
::::* '''Web''':


== About CureMILS ==
<div class="mw-collapsible-content">
:::: Led by Prof. Dr. Alessandro Prigione of the Heinrich Heine University, the CureMILS project aims to employ a novel approach to enable drug discovery of MILS.


===Aims===
[[File:MitoFit-QCS.jpg|right|400px|MitoFit-QCS]]
:::: The project aims to use iPSCs and reprogramming-drived drug discovery for finding therapies against MILS. A personalized medicine approach will be applied and compound screenings on patient-derived neural cells will be carried out. Brain organoids and multi-omics analysis will be used for validations.
:::: Many commonly raised issues of O2k-technical support are solved in the newest version of [[DatLab]].      
:::::: 1. Establishment of PDE5 inhibitors as reference drugs for MILS
:::::: 2. Large-scale screen of marketed compounds in MILS neural cells
:::::: 3. Validations of hit compounds in MILS neural cells
:::::: 4. Validations of hit compounds in neural cells carrying LS-associated Complex I mutations
:::::: 5. Computational analysis of MILS neural cells and treatments


===Objectives===
:::: The '''O<sub>2</sub> sensor and O2k chamber tests''' are important to eliminate instrumental artefacts (instrumental quality control, QC), distinguished from assay QC addressing problems of [[solution protocols]] (preparation of chemicals), [[sample]] preparation protocols (such as [[mitochondrial preparations]]), and [[SUIT protocols]].
:::: '''WP1''' - [[Prigione Alessandro| Dr. Alessandro Prigione]], Heinrich Heine University
::::# Clean O2k-chambers and contamination-free incubation medium are required.  
:::: The goal of WP1 is to collect all the experimental, clinical, and regulatory information required to develop an ODD plan for the PDE5i sildenafil.
::::# Analysis of DatLab files recorded in instrumental QC tests is essential.       
::::* Confirmation of the PDE5i effects in all MILS-NPCs
::::# Biological experiments are not suitable for trouble shooting.
::::* Actions of PDE5i on mitochondrial polarization in MILS-NPCs


::::* Mitochondrial mechanisms of action of PDE5i in MILS-NPCs
:::: '''1. O<sub>2</sub> sensor test'''
:::: The [[OroboPOS|OroboPOS]] (polarographic oxygen sensor) requires regular service at intervals - these may be more than 1 year. SOPs are available to determine if a sensor service is required at an earlier or later date:
::::» O<sub>2</sub> sensor test: [[Oxygen_sensor_test |'''QC1: Oxygen sensor test''']]     


::::*  Engage with regulatory and patenting experts
:::: '''2. O2k-chamber test'''
:::: If all quality control criteria of the O<sub>2</sub> sensor test are met, the operator can be assured that the quality of the sensor signal is acceptable. Next, the quality of the O2k-chamber assembly has to be tested, described in detail:
::::» O2k-chamber test: [[Oxygen flux - instrumental background |'''QC2: Instrumental O<sub>2</sub> background test''']]     


:::: '''WP2''' - Ole Pless, Fraunhofer IME
</div>
:::: The goal of WP2 is to carry out a phenotypic compound screening in MILS-NPCs to identify marketed compounds than can be suggested to be repositioned for MILS.
</div>
[[File:Expand.png|right|45px |Click to expand or collaps]]
<div class="toccolours mw-collapsible mw-collapsed">
'''Advanced topics'''
<div class="mw-collapsible-content">
::» O2k-Workshop self-study material: [https://wiki.oroboros.at/index.php/Virtual_O2k-Workshop_self-study_material#O2k-Advanced O2k-Applications: Simultaneous determination of O2 and H2O2 fluxes]


::::*  Primary screen and hit identification
:: You may also find the answers to more advanced topics using the navigation menu above or simply by using the Bioblast search function.:  
{|
|
| &nbsp;&nbsp;&nbsp;
| &nbsp;&nbsp;&nbsp;
| [[Image:O2k-Hardware icon.jpg|50px|link=https://wiki.oroboros.at/index.php/MitoPedia:_O2k_hardware |MitoPedia: O2k hardware]]
| &nbsp;&nbsp;&nbsp;
| &nbsp;&nbsp;&nbsp;
| [[Image:DatLab icon.jpg|50px|link=https://wiki.oroboros.at/index.php/MitoPedia:_DatLab |MitoPedia: DatLab]]
| &nbsp;&nbsp;&nbsp;
| &nbsp;&nbsp;&nbsp;
| [[Image:SUIT icon.jpg|50px|link=https://wiki.oroboros.at/index.php/MitoPedia:_SUIT |MitoPedia: SUIT]]
| &nbsp;&nbsp;&nbsp;
| &nbsp;&nbsp;&nbsp;
| [[Image:O2k-Protocols.jpg|50px|link=http://wiki.oroboros.at/index.php/O2k-Procedures |O2k-Procedures]]
| &nbsp;&nbsp;&nbsp;
| &nbsp;&nbsp;&nbsp;
| [[Image:O2k-Manual.jpg|50px|link=http://wiki.oroboros.at/index.php/O2k-Manual|O2k-Manual]]
| &nbsp;&nbsp;&nbsp;
| &nbsp;&nbsp;&nbsp;
| [[Image:PlayVideo.jpg|50px|link=http://wiki.oroboros.at/index.php/O2k-Videosupport |O2k-Videosupport]]
| &nbsp;&nbsp;&nbsp;
| &nbsp;&nbsp;&nbsp;


::::* Hit confirmation and prioritization
| [[Image:O2k-GlossaryFaq icon.jpg|50px|link=https://wiki.oroboros.at/index.php/MitoPedia:_O2k-Open_Support |MitoPedia: O2k-Open Support]]
| &nbsp;&nbsp;&nbsp;
| &nbsp;&nbsp;&nbsp;


::::* Hit validations in different MILS-NPCs
|}
::::::# '''MitoPedia: O2k''': find information quickly with MitoPedia, with lists of key words and links to relevant pages.
::::::## [[MitoPedia: O2k hardware]]
::::::## [[MitoPedia: DatLab]]
::::::## [[MitoPedia:_SUIT ]]
::::::# [[O2k-Procedures]]: explain various applications of the O2k with O2k-Demo experiments
::::::# [[O2k-Manual]]: topic specific manuals with step by step help
::::::# [[O2k-Videosupport]]: provides valuable assistance, complementary to the O2k-Manual
::::::# [[MitoPedia: O2k-Open Support|O2k-Glossary]]: full list of key words and links to relevant pages.


:::: '''WP3''' - Dr. Werner Koopman, University of Luxembourg
</div>
:::: The goal of WP3 is to elucidate the mitochondrial and functional effects of PDE5i and top-10 compounds in MILS neural cells (including neural progenitors, post-mitotic neurons, and brain organoids) and to assess their blood-brain barrier (BBB) permeability.
</div>
::::* Effects of compounds on mitochondrial profiling of MILS-NPCs
== Ask an O2k-Expert and the O2k-Open Support agreement ==
::::* Effects of compounds on NAD metabolites in MILS-NPCs
::::* Effects of compounds in MILS neurons
::::* Effects of compounds in MILS brain organoids
::::* Patient-specific BBB permeability of repurposable compounds


:::: '''WP4''' - Dr. Frank Edenhofer,University of Innsbruck
:::: We give you the tools to be self-sufficient, but sometimes you need expert advice or help solving a technical problem. The Oroboros experts will be happy to help in using our O2k-Open Support system. » [https://www.oroboros.at/index.php/o2k-technical-support '''Contact Support''']     
:::: The goal of WP4 is to determine whether the repurposable compounds (PDE5i and the top-10 compounds) may be effective not only in MILS neural cells carrying MT-ATP6 mutations but also in neural cells carrying other LS-associated mtDNA mutations in Complex I (MT-ND3 gene).  
::::» [[O2k-Open Support agreement]]
::::* Direct reprogramming of MILS-iNPCs
::::» [[O2k repair]]
::::* Validations of PDE5i in MILS-iNPCs
::::* Direct reprogramming of Complex I-mutant iNPCs
::::* Comparison of MILS-iNPCs and Complex I-mutant iNPCs
::::* Mitochondrial profiling in treated iNPCs


:::: '''WP5''' - Dr. Antonio del Sol, University of Luxembourg
:::: The goal of WP5 is to generate omics analysis of MILS neural cells, and to develop a model of the disease and of the suggested treatments.
::::* Proteomics and metabolomics of MILS neural cells
::::* Transcriptomics and epigenomics of MILS neural cells
::::* Network-based model of MILS in human neural cells
::::* Proteomics and metabolomics of treated MILS neural cells
::::* Transcriptomics and epigenomics of treated MILS neural cells
::::* Network-based model of repurposable compounds
== Coordinator==
::::*  [[Prigione Alessandro| Alessandro Prigione, MD, PhD]] - Department of General Pediatrics, Neonatology, and Pediatric Cardiology at Heinrich Heine University, DE - https://www.neurosciences-duesseldorf.de/principal-investigators-and-junior-researchers/alessandro-prigione OR https://www.hhu.de/en/


[[File:O2k-Network.png|left|100px|O2k-Network|link=O2k-Network]]
== The O2k-Network: An additional resource ==


:::: The Oroboros O2k-Network serves to connect and support: Contact for advice on applications of the O2k and high-resolution respirometry - the global network in mitochondrial physiology.      
== Network ==
===Participants/Beneficiaries===
::::* [https://www.ime.fraunhofer.de/en/Research_Divisions/business_fields_TM/screeningport.html Fraunhofer IME, Department ScreeningPort], DE
::::* [https://www.uibk.ac.at/molbiol/index.html.en Institute for Molecular Biology, University of Innsbruck], AT
::::* [https://www.radboudumc.nl/en/research/departments/biochemistry Radboud University Medical Center, Biochemistry], NL
::::* [https://www.helsinki.fi/en/researchgroups/stem-cells-and-metabolism-research-program University of Helsinki, Research Program of Stem Cells and Metabolism], FI
::::* [http://www.ighz.edu.pl/en/ Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences, Department of Molecular Biology], PL
::::* [https://www.ddsp.univr.it/?ent=home&page=dipartimento&lang=en Verona University, Department of Diagnostics and Public Health], IT
::::* [https://wwwen.uni.lu/lcsb Luxembourg Centre for Systems Biomedicine (LCSB) University of Luxembourg], LU


::::* [https://www.mitopatients.org/ International Mito Patients (IMP)]
::::: '''»''' The O2k-Network Labs: [[O2k-Network|» O2k-Network]]      
=== Collaborators ===
::::* [https://neuropaediatrie.charite.de/ Charité University, Clinic for Pediatrics and Neurology], DE


::::* [https://www.uniklinik-duesseldorf.de/en/department-of-general-paediatrics Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Heinrich Heine University], DE
::::: '''»''' [[O2k-Network_discussion_forum|O2k-Network discussion forum]]      


::::* [https://www.oroboros.at/ Oroboros Instruments GmbH], AT
:::: '''»''' [[Oroboros Laboratories|Oroboros O2k-Laboratory]] - open for innovation and cooperation.
:::: '''»''' [[Oroboros_Science_Scholarship|Oroboros Science Scholarships]] - are offered for focused research projects on mitochondrial physiology and high-resolution respirometry     


::::* [https://www.istituto-besta.it/ Foundation IRCCS Neurological Institute C. Besta, Unit of Molecular Neurogenetics], IT
[[Category:O2k-Open Support]]


::::* [http://eng.biometra.unimi.it/ecm/home University of Milan, Department of Medical Biotechnology and Translational Medicine], IT


::::* [https://www.molgen.mpg.de/2168/en Max Planck Institute for Molecular Genetics], DE
::::* [http://mitonet.org/en/ Deutsches MITONET e.V., Friedrich-Baur-Institut], DE


<br />
</div>


== Oroboros project involvement ==
| style="border:1px solid transparent;"|
:::: Oroboros is a collaborator on the project providing infrastructure and expertise required to conduct respirometric measurements for the project.


<!--        2ND BOX | IN FOCUS - RIGHT        -->
| id="mp-right" class="MainPageBG" style="width:25%; border:1px solid #cedff2; padding:0; background:#f5faff; vertical-align:top;"|


== CureMILS events ==
<div id="mp-tfa-h2" style="margin:0.5em; background:#2856ba; font-family:inherit; font-size:120%; font-weight:bold; border:1px solid #a3bfb1; color:#ffffff; padding:0.2em 0.1em;"></div>




{{#ask:[[Category:Publications]] [[Additional label::CureMILS]]
<div id="mp-itn" style="padding:0.1em 0.6em;">
|?Was published in year=When
[[File:O2k-support system.jpg|center|350px|Oroboros support system]]</div>
|?Has title=Where
|format=broadtable
|limit=5000
|offset=0
|sort=Was published in year
|order=ascending
}}




== CureMILS publications ==


== CureMILS  dissemination ==


==Links==
===Social Media===
===Research Networks===


== References ==
== Additional information ==
== Support ==
The EJP RD initiative has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement N°825575. EJP RD is coordinated by INSERM, France.
[[File:Flag yellow low.jpg|left|100px]]


<br/>
<!--        NEXTGEN-O2K BANNER        -->
<br/>
<div style="margin:0.5em; background:#cedff2; font-family:inherit; font-size:120%; font-weight:bold; border:1px solid #a3b0bf; color:#000; padding:0.2em 0.1em;">Funding acknowledgments</div>
<br/>
<div id="mp-itn" style="padding:0.1em 0.1em;">[[File:Template NextGen-O2k.jpg|center|350px|NextGen-O2k]]</div>
* [https://www.ejprarediseases.org/index.php/funded-projects-2020/ Funded projects]
|}
<br />
</div>

Latest revision as of 13:59, 29 July 2021


                  

O2k-Open Support

User talk:Tindle Lisa/My sandbox Support page v2

Currently Asked Questions - »O2k-Open Support alert« 


Retrieved from "https://wiki.oroboros.at/index.php?title=User_talk:Tindle_Lisa/My_sandbox_Support_page_v2&oldid=219395"
Powered by MediaWiki
Powered by Semantic MediaWiki