Investigation of alpha-synuclein pathogenic mechanisms with human stem cells and neurons

Lead Research Organisation: University of Edinburgh
Department Name: Sch of Biological Sciences

Abstract

Parkinson's disease (PD) is a progressive degenerative disorder of the brain. A mixture of environmental and genetic triggers are thought to cause the sporadic forms of this condition. A common link between all cases of PD is the unusual and damaging behaviour of a protein known as alpha-synuclein. This protein is present in neurons of all people, and is usually benign. However, in people with Parkinson's and some forms of dementia, alpha-synuclein takes on unusual shapes and becomes toxic to neurons, eventually killing them. A second unpleasant property of this protein is that it is thought to travel through the brain spreading disease. This behaviour may be similar to how prion protein from infected beef can spread from gut neurons into the spinal cord, and eventually into the brain causing severe neurological problems. We propose to use live human neurons to model the disease-causing behaviour of alpha-synuclein in the laboratory. We have recently published induced pluripotent stem cells (iPSCs) from a patient with 4 copies of the gene encoding alpha-synuclein, instead of the normal two copies. This patient and about half the members of her family get a severe, early-onset form of PD with dementia. The neurons made from PD iPSCs produce twice as much alpha-synuclein protein as control neurons from an unaffected 1st-degree relative of this patient. The PD and healthy neurons will be used in comparative studies to investigate any problems caused by over-production of alpha-synuclein. In parallel work, human embryonic stem cells (hESCs) were genetically modified to over-produce alpha-synuclein at a wide range from 2-fold to 6-fold above normal levels. Both iPSCs and hESCs will be used to investigate the unusual behaviour of alpha-synuclein including its neurotoxic properties. If reproducible, disease-causing behaviour is observed, these cells will be ideal for modeling PD and understanding how alpha-synuclein kills neurons. This system will be used for screening drugs that could stop the harmful behaviour of alpha-synuclein. Several pilot screens of a select number of compounds will be performed to determine the feasibility of this approach. Potent drugs that prevent the misfolding and pathological behaviour of alpha-synuclein will change the face of PD and dementia treatment by stopping or severely retarding the progression of the disease.

Technical Summary

Parkinson's disease (PD) is a progressive neurodegenerative disorder with no known cure. A prevailing model of PD progression suggests that the small pre-synaptic protein alpha-Synuclein (aSyn) misfolds and forms aggregates the cause neuronal dysfunction and death. Futhermore, these misfolded aggregates are proposed to travel through the brain in a prion-like manner. The exact mechanism of how aSyn causes neuronal death is not known, but significant evidence suggests it directly compromises mitochondrial function. Neuroprotective compounds that prevent or reduce aSyn toxicity halt or slow the progression of PD. Using iPSC lines from a patient with alpha-synuclein triplication, and hESCs engineered to overexpress aSyn, I propose to establish a robust, semi-automated fluorescence-based system to read-out alpha-synuclein phenotypes.

Planned Impact

Neuroscience and stem cell researchers: The work proposed in this project will investigate the pathogenic behaviour of a central protein at the root of Parkinson's. This will be looked at for the first time in authentic human Parkinson's neurons. The cell lines (iPSC and hESC) generated as part of this study will be of extreme interest to other academics wishing to studying this condition in the lab. All cell lines will be shared post-publication, and some cell lines will be shared pre-publication.

Local research community: There are several labs in the MRC CRM and the Centre for Neuroregeneration interested in using human pluripotent stem cells to model diseases. I have shared by iPSC and neural induction protocols with Prof Ian Wilmut and Prof Siddharthan Chandran, and will continue to share expertise with labs doing similar work.

Wider academic community: I will publish all findings in peer-reviewed journals in an open-access format, and make all protocols available through my website. I will also present my work an scientific conferences with a diverse audience, including the 3rd World Parkinson Congress. My work may influence the way scientists in other neurodegenerative fields, such as Alzheimer's, approach disease modelling and drug screening.

Junior Researchers: Over the course of the proposed grant, several undergraduate honours students and PhD students will be involved with several aspects. Most of the preliminary data in this proposal has been generated by PhD students.

Biotech/pharma industry: My major goal it to established a high-content screening platform to identify novel drugs or novel activities of known drugs. If the platform proves robust I would anticipate considerable interest from companies endeavouring to discover new treatments for intractable conditions, such as Parkinson's. Furthermore, companies such as Antoxis, that design drugs, but do not have the capability to screen them will also be keenly interested in collaborating.

General Public: My recent published work on Parkinson's iPSCs was covered by BBC news (on-line), The Scotsman, The Times, The Daily Telegraph, and most importantly, The Metro. I also participated in a 40-min discussion on the BBC World Service (www.bbc.co.uk/programmes/p00jnf02). I have also accepted an invitation to The Vatican to present my work at a "Responsible Stem Cell Research" conference in April 2012. They are very keen that am doing stem cell research without destroying embryos. There is a strong personal interest in my research by people with Parkinson's and their family and carers. I present my research to people with Parkinson's on a regular basis (~9 times in 2011 so far). I also host a special interest group of people with Parkinson's that are keenly interested in basic research. We have meet twice at the MRC CRM this year, with a third meeting scheduled in December, 2011. The main purpose of the group is to raise awareness of Parkinson's research and increase participation of patients in research studies and clinical trials.

Medicine: In the long-term my work may directly or indirectly lead to disease-modifying drugs for Parkinson's. This would have a very large impact on the way this condition is treated, and on the quality of life of people living with Parkinson's. The methodology used in this proposal may also be applicable to other neurodegenerative diseases that have misfolded proteins driving it. For example, Tau for Alzheimer's and TDP-43 for motor neurone disease

Publications

10 25 50

 
Description Carnegie PhD Scholarship
Amount £62,696 (GBP)
Organisation Carnegie Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2014 
End 09/2017
 
Description Developing an assay to measure neuron-to-neuron spread of alpha-synuclein on a microfluidcs platform
Amount £164,603 (GBP)
Funding ID BIOSCIE2009 
Organisation UCB Pharma 
Sector Private
Country United Kingdom
Start 03/2019 
End 03/2020
 
Description UCB Industrial partnership
Amount £244,031 (GBP)
Funding ID Not known 
Organisation UCB Pharma 
Sector Private
Country United Kingdom
Start 03/2016 
End 02/2018
 
Description Wellcome Trust Clinical PhD Fellowship
Amount £231,504 (GBP)
Funding ID 203646/Z/16/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2016 
End 08/2019
 
Title Alpha-synuclein knock-out human embryonic stem cells 
Description We used CRISPR/Cas9 to knock-out the Parkinson's-related gene, alpha-synuclein (aSyn), in RC17 human embryonic stem cells. We generated a number of cell lines that are aSyn-null and confirmed thet are protein-null by western blotting. We have published the lines in the following paper: Chen Y, Dolt KS, Kriek M, Baker T, Downey P, Drummond NJ, Canham MA, Natalwala A, Rosser S, Kunath T. Engineering synucleinopathy-resistant human dopaminergic neurons by CRISPR-mediated deletion of the SNCA gene. Eur J Neurosci. 2019 Feb;49(4):510-524. doi: 10.1111/ejn.14286. 
Type Of Material Cell line 
Year Produced 2019 
Provided To Others? Yes  
Impact These lines have so far been shared with Dr David Beckham at UC Denver under MTA for a collarative project, and Dr Malin Parmar at Lund University. 
URL https://onlinelibrary.wiley.com/doi/full/10.1111/ejn.14286
 
Title G51D SNCA human iPS cell lines 
Description A set of six human induced pluripotent stem cell lines were derived from a mother-daughter pair. Three cell lines with the G51D SNCA heterozygous mutation were derived from the daughter, and three control iPSC lines were derived from the mother who did not carry this mutation. 
Type Of Material Cell line 
Year Produced 2015 
Provided To Others? Yes  
Impact These cell lines have been deposited into the European Bank of induced Stem Cells (EBiSC) and they have further distributed to research group who are interested in modelling Parkinson's and dementia with Lewy bodies. 
 
Title Protocol of cryopreservation of human dopaminergic neural cells 
Description We have released a highly optimised method for cryopreservation of human dopaminergic neural cells differentiated from human embryonic stem cells and human induced pluripotent stem cells 
Type Of Material Technology assay or reagent 
Year Produced 2020 
Provided To Others? Yes  
Impact The methods and manuscript are recently released (12th February 2020), and impact is not known yet. However, these methods have been instrumental for a number of collaborations, including Dr Eilis Dowd at National University of Ireland, Galway, and Prf J. David Beckham at University of Colorado 
URL https://www.biorxiv.org/content/10.1101/2020.02.11.944272v1
 
Title Transgenic human ES cell lines 
Description A collection of 12 clonal transgenic human embryonic stem cell were generated that express differing levels of the Parkinson's-related gene, SNCA, which encodes for the alpha-synuclein protein 
Type Of Material Cell line 
Provided To Others? No  
Impact The collection of lines was used a preliminary data for an MRC Project grant application entitled "Investigation of alpha-synuclein pathogenic mechanisms with human stem cells and neurons" This was awarded and started 1st November, 2012 
 
Title Triplication SNCA and control iPS cell lines 
Description Collection of iPS cell lines derived in my laboratory from a patient with familial Parkinson's caused by triplication of the SNCA gene which encodes the alpha-synuclein protein. Control iPS cell lines were also established from a non-affected first-degree relative of this patient. 
Type Of Material Cell line 
Year Produced 2013 
Provided To Others? Yes  
Impact These cell lines were the foundation of my Nature Communications paper (Devine et al 2011). These cell lines have been shipped to three laboratories, but publications have not resulted yet. 
 
Description Antoxis 
Organisation Antoxis Limited
Country United Kingdom 
Sector Private 
PI Contribution Testing Antoxis novel compound in cell-based model of oxidative stress and Parkinson's disease. The work is the basis of an industrial SULSA PhD student and will be part of her PhD thesis and one future publication.
Collaborator Contribution Provided a novel anti-oxidant compound and expert advice on experimental design.
Impact This is multi-disciplinary, as the student is doing experiments in biology and chemistry. She is also using electron paramagnetic resonance (EPR) in collaboration with the School of Chemistry, as part of her work. The student has completed her PhD work, and the paper is under review at Scientific Reports. The title is "A novel mitochondrial enriched antioxidant protects neurons against acute oxidative stress". The authors are: Nicola J. Drummond, Nick O. Davies, Janet E. Lovett, Mark R. Miller, Graeme Cook, Thomas Becker, Catherina G. Becker, Donald B. McPhail, Tilo Kunath
Start Year 2011
 
Description Antoxis 
Organisation Scottish Universities Life Sciences Alliance
Country United Kingdom 
Sector Academic/University 
PI Contribution Testing Antoxis novel compound in cell-based model of oxidative stress and Parkinson's disease. The work is the basis of an industrial SULSA PhD student and will be part of her PhD thesis and one future publication.
Collaborator Contribution Provided a novel anti-oxidant compound and expert advice on experimental design.
Impact This is multi-disciplinary, as the student is doing experiments in biology and chemistry. She is also using electron paramagnetic resonance (EPR) in collaboration with the School of Chemistry, as part of her work. The student has completed her PhD work, and the paper is under review at Scientific Reports. The title is "A novel mitochondrial enriched antioxidant protects neurons against acute oxidative stress". The authors are: Nicola J. Drummond, Nick O. Davies, Janet E. Lovett, Mark R. Miller, Graeme Cook, Thomas Becker, Catherina G. Becker, Donald B. McPhail, Tilo Kunath
Start Year 2011
 
Description UCB 
Organisation UCB Pharma
Department UCB Celltech
Country United Kingdom 
Sector Private 
PI Contribution This research is part of a BBSRC CASE PhD studentship in collaboration with Dr. Alison Hulme at the School of Chemistry. Custom-designed helical forms of alpha-synuclein are being generated by the student. These will be examined for their ability to prevent pathogenic, beta-sheet, folding of alpha-synuclein.
Collaborator Contribution Providing protein production and expert experimental advice. UCB is also offering to generate antibodies to novel conformers of alpha-synuclein generated by the PhD student.
Impact This project involves both chemistry and biology. Recombinant protein production and chemical synthesis of helical peptides, as well as biophysical characterization of the compounds.
Start Year 2012
 
Description Alliance Of Scottish Parkinson's Nurse Specialist Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Health professionals
Results and Impact I presented current research in my lab funded by Parkinson's UK, The Cure Parkinson's Trust, and the MRC. I had 4-5 insightful questions after my talk.

I received very detailed feedback from the audience including scores out of 10, and lots of written feedback. More than half the scores were 8/10, 9/10, or 10/10. Some comments were 1. A bit over my head but incredibly interesting and encouraging that they are still searching for a cure. He was very enthusiastic about his subject and extremely knowledgeable. 2. Excellent talk but more scientific than my brain could cope with. 3. Interesting but not clinical enough. 4. Very knowledgeable speaker with an obvious huge breadth of information to deliver.
Year(s) Of Engagement Activity 2014
 
Description BBC World Service interview on The Forum 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact I was part of a 3 person panel discussing Universal Rights. The other panel members were Baroness Mary Warnock and Dr Kaushik Basu, Senior Vice President and Chief Economist of the World Bank.
http://www.bbc.co.uk/programmes/p00jnf02

Unsure.
Year(s) Of Engagement Activity 2011
 
Description BNA Festival 2015 Talk 1 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation keynote/invited speaker
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact On 13th April, I presented a seminar in the "Human stem cell models of neurodegenerative disease" session of the BNA 2015 Festival in Edinburgh.

Renewed collaboration with Dr Selina Wray which has led to a grant application the Wellcome Trust with Dr Michele Zagnoni (University of Strathclyde).
Year(s) Of Engagement Activity 2015
URL http://www.bna2015.org/programme/details/?session=11523&theme=G
 
Description BNA Festival 2015 Talk 2 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation keynote/invited speaker
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact On 14th April I presented at talk entitled "Differentiation of clinical grade human pluripotent stem cells into midbrain dopaminergic neurons" in the "Modelling human disease in a dish: implications for understanding neurodegeneration and for development of novel therapies" session at the BNA 2015 Festival

Reinforced collaboration with Prof Meng Li and Prof Malin Parmar
Year(s) Of Engagement Activity 2015
URL http://www.bna2015.org/programme/details/?session=11534&theme=B
 
Description BioDundee Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation keynote/invited speaker
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact On 2nd June, 2015 I presented a lecture at the BioDundee conference in Dundee and entertained questions afterwards. The audience was a mix of academia, industry, and government individuals

Not aware of any impact.
Year(s) Of Engagement Activity 2015
URL http://www.biodundee.co.uk/events/3143/BioDundee+Conference+2015/
 
Description British Science Festival - Bradford 2015 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact On 9th September, 2015, I was part of a panel discussion on the topic of getting old - "Who wants to live forever?". Prof Anthea Tinker, sociologist from KCL, James Stark, medical historian from University of Leeds, and myself consisted of the panel.

There was a tremendous amount of discussion after our short talks.
There were also some on-line press about the event that would somewhat inaccurate!
http://www.express.co.uk/news/science/604082/Vitamins-waste-of-time-fasting-live-longer
Year(s) Of Engagement Activity 2015
URL http://www.britishscienceassociation.org/Blog/new-thinking-about-getting-older
 
Description Cafe Scientifique Dunkeld 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact On 9th December, 2014 I presented by research on Parkinson's to the Dunkeld branch of Cafe Scientifique. It was followed by 30min of very stimulating discussion from the attendees.

Attendees commented after the event that I certainly removed some of the confusion around stem cells in their minds, and they were more in favour of stem cell research after my talk and discussions.
Year(s) Of Engagement Activity 2014
URL http://tulliemet-perthshire.org.uk/main/index.php/cafesci
 
Description Cafe Scientifique Edinburgh 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact My Cafe Scientifique talk on 14th July 2014 in Edinburgh promoted over 40min of additional discussion.

The organiser recieved an email from a participant stated it was one of the most engaging Cafe Scientifique he had attended.
Year(s) Of Engagement Activity 2014
 
Description Cardiff seminar 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Local
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact I presented my current research to a group of 40-50 basic and clinician scientists at Cardiff University.

I have positive feedback on my lecture from my host Dr. William Davies. I also had useful post-seminar discussions with Prof Anne Rosser about scientific direction.
Year(s) Of Engagement Activity 2013
 
Description Co-host 2015 Edinburgh Parkinson's Lecture - Patrick Brundin 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach Regional
Primary Audience Supporters
Results and Impact On 22nd April, I co-hosted Patrik Brundin's Edinburgh Parkinson's Lecture with Prof Ken Bowler. I also organised a showcase of Edinburgh researchers for Arthur Roach and Patrik Brundin to hear about. They included Prof Manfred Auer, Prof Kathryn Ball, Dr Thomas Becker, Dr Alison Hulme, Dr Maria Doitsidou, Dr Lysimachos Zografos of Parkure Ltd, and myself.

Lots of ideas were exchanged and led to a collaboration between Patrik Brundin and Dr Zografos, and initiated a collaboration with Dr Doitsidou and myself.
Year(s) Of Engagement Activity 2015
URL http://www.edinburghparkinsons.org/edinburgh-parkinsons-lecture-2015/
 
Description Congress on the Italian (ABCD) Association of Cell Biology and Differentiation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation keynote/invited speaker
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Invited speaker at conference and excellent questions after mu presentation

Renewed collaboration with Dr Luciano Conti at the University of Trento
Year(s) Of Engagement Activity 2015
URL http://abcd2015.azuleon.org/welcome.php
 
Description Dalriada Conversations 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact On 25th November 2016, I gave a 40 minute talk on stem cells and potential applications for Parkinson's disease. This was followed by 60min of questions and discussions. Prof Ken Bowler (Edinburgh branch of Parkinson's UK) is one of the co-organisers of Dalriada Conversations and set up the invitation to speak. Nick Stroud, another co-organiser, sent me a card in the post dated 26th November that read "Dear Tilo, Just a wee note to thank you very much for giving up your evening to come and have a chat with us in Portobello. Your work is fascinating, and you have a very engaging way of talking about it. And even though you made it sound really challenging work, right at the frontiers of human knowledge, I think you spared us several layers of just how complicated and minutely detailed this work is! We all appreciated this from a very personal point of view, as well: it's good to know that our dear Ken has so much talent on his side. I'm sorry we kept you from your family, so appreciate your visit even more. And we certainly all wish you the very best with your continuing research. Thank you!! Nick Stroud"

At the end of the discussions I met the mother of researcher at UCL that has recently spun out a company that works on molecules that may have therapeutic potental for Parkinson's. I gave the woman my contact details, and asked for he daughter to get in contact with me.

On 8th December, 2015 I received an email from Dr Jemma Gatliff introducing herself as the daughter of the woman I meet at Dalriada Conversations on 25th November. She is the CEO and co-founder of Keregen Therapeutics, a spin-out compnay of UCL that has developed small molecule activators of NRF2, a transcription factor that activates antioxidant defense pathways. Her company is a OneStart 2015 finalist for Europe, which picks the top 10 start-up companies in the life sciences and healthcare sector for that year.
Dr Gatliff and I had our first in-person meeting on 28th December, 2015 at our institute MRC Centre for Regenerative Medicine, to share our respective knowledge and data. We also discussed how we could work together and options for potential funding. The next meeting be in her labs in London.
Year(s) Of Engagement Activity 2015
 
Description Edinburgh Enlightenment lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact On 31st March, 2012 I gave a public lecture on my research at the Edinburgh International Science Festival. This was part of a series of diverse lectures, and the audience size was about 100.

Very stimulating discussions, and interesting interactions between the different speakers.
Year(s) Of Engagement Activity 2012
 
Description Edinburgh Fringe Festival 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact John MacPhee and I put on a single show on 6th August 2017 as part of the Cabaret of Dangerous Ideas (CODI) series in the Edinburgh Fringe Festival. Over 110 tickets were sold, and we were the 3rd largest audience for the CODI series. Lots of very interesting discussion occurred during the event and afterwards, and we have been invited for a repeat performance on 14th February 2018 to the Edinburgh Branch of Parkinson's UK.
Year(s) Of Engagement Activity 2017
URL https://edinburghfestival.list.co.uk/event/775782-eradicate-parkinsons/
 
Description Edinburgh Parkinson's Lecture 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Participants in your research and patient groups
Results and Impact I have co-organised all the Edinburgh Parkinson's Lecture with Parkinson's UK (Ken Bowler) and the Scottish Parkinson's Nurses Association. It was presented by Prof Roger Barker (2012), Prof Ray Chaudhuri (2013), and Prof Anthony Schapira (2104) at the Royal College of Physicians to over 300 people on each occasion. The audience consisted of people with Parkinson's, their partners/relatives, caregivers, and scientists.

These presentations have major impacts to the Parkinson's patients in attendance and their loved ones. The weblink highlights for the 2013 lecture notes a quote from Shona Lawson (Support Worker from West Lothian). A patient in her area told her that lecture gave her the confidence to pick up the phone to my nurse and ask for some non-motor issues to be addressed.
Year(s) Of Engagement Activity 2012,2013,2014
URL http://www.edinburghparkinsons.org/the-edinburgh-parkinsons-lecture-2013-2/
 
Description Gavin Hastings and Warren Gatland visit to research lab 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact On 8th March, 2017 I hosted a lab visit for Gavin Hastings (Scottish International Rugby player) and Warren Gatland (coach of the British and Irish Lions Rugby team). The visit was to learn more about a cell therapy for Parkinson's (projected funded by the MRC), raise awareness for Parkinson's and to support the charity The Cure Parkinson's Trust. A BBC television crew filmed the event and it appeared on the 6 o'clock news on 8th March, 2017.
Other on-line print and video (YouTube) was also used to capture the event.
Year(s) Of Engagement Activity 2017
URL https://www.youtube.com/watch?v=tvPDFibrDAo&t=1s
 
Description Host Lay reviewer training for Parkinson's UK 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Supporters
Results and Impact On 26th August, 2015, I hosted a lay reviewer training day in our institute MRC Centre for Regenerative Medicine. The main organiser was Isabelle Abbey-Vital. There was lots of interesting discussions through-out the day. I presented the perpective of a researcher submitting grants to Parkinson's UK, and also as a reviewer for Parkinson's UK, and other agencies.

Reviewers were thoroughly trained and I expect most are now reviewing grants for Parkinson's UK now.
Year(s) Of Engagement Activity 2015
 
Description Host Parkinson's Research Interest Group-Counsel 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? Yes
Type Of Presentation Workshop Facilitator
Geographic Reach Regional
Primary Audience Participants in your research and patient groups
Results and Impact This Edinburgh Research Interest Group meeting took place on Saturday, 8th February, 2014 at the MRC Centre for Regenerative Medicine. The invited speaker was Dr. Carl Counsel from Aberdeen speaking about his project "What changes happen over time for people with Parkinson's and their carers?" I co-hosted and facilitated this meeting with Prof Ken Bowler, the Chair of this Research Interest Group. The audience consisted of 32 people, including about people with Parkinson's and their partners. The seminar and questions was followed by an informal lunch and general discussions.

The feedback from the patients and partners/carers was extremely positive. We received a realistic picture of the true prognosis of a Parkinson's diagnosis. The group was also strengthened in their resolve to change NHS practices in the Lothian area to improve care especially in the later stages of this condition.
Year(s) Of Engagement Activity 2014
URL http://www.edinburghparkinsons.org/talk-dr-carl-counsell/
 
Description Innovate UK/NC3Rs consortia building workshops for Non-Animal Technologies 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact On 19th February, 2015 I attend a workshop on Innovate UK/NC3Rs consortia building workshops for Non-Animal Technologies and also presented a brief presentation.

Afterwards I have some interaction with Dr Ben Cantwell of Kromek Group regarding phenotypic screening.
Year(s) Of Engagement Activity 2015
 
Description Institute site visit by Arbroath branch of PUK 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Type Of Presentation Workshop Facilitator
Geographic Reach Regional
Primary Audience Participants in your research and patient groups
Results and Impact On 9th April, 2012 I hosted 4 members of Arbroath branch of PUK. I present some my research to them, and also gave them a tour of the institute.

Very positive feedback from this visit.
Year(s) Of Engagement Activity 2012
 
Description Institute site visit from East Lothian Branch of Parkinson's UK 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Type Of Presentation Workshop Facilitator
Geographic Reach Regional
Primary Audience Participants in your research and patient groups
Results and Impact On 20th February, 2012 I hosted members of the East Lothian branch of Parkinson's UK. I presented my research to them and also gave them a tour of our institute.

Excellent feedback from the branch members and they donated £4512 to Parkinson's UK towards my project (F-0902).
Year(s) Of Engagement Activity 2012
 
Description Invited external speaker at NUI Galway 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach Regional
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Several questions after the seminar and several one-to-one meetings within the REMEDI institute.

In-depth discussions and emails with Prof Mary Murphy regarding one of the differentially-expressed genes I presented during my seminar.
Year(s) Of Engagement Activity 2015
URL http://www.remedi.ie/news/invited-speaker-dr-tilo-kunath
 
Description Menzies Trust 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Type Of Presentation Workshop Facilitator
Geographic Reach National
Primary Audience Supporters
Results and Impact Hosted a visit of two representatives from the J Macdonal Menzies Trust at the MRC Centre for Regenerative Medicine on Friday, 20th September, 2013.

Two representatives from the J Macdonal Menzies Trust have made sizable donations to Parkinson's UK it specifically support my lab.
Year(s) Of Engagement Activity 2013
 
Description Organiser and host of Edinburgh Research Interest Group on 12th January 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact I invited a researcher, Dr Thanasis Tsanas, to speak with Parkinson's patients and carers, and nurse specialists at the Edinburgh Research Interest Group at my workplace - the MRC Centre for Regenerative Medicine at the University of Edinburgh. The intended purpose was to inform PD patients living in Lothian of the research going on in Dr Tsanas' group. His PhD student, Anne Steinberg, also spoke and advertised that she is recruiting patients to participate in a research study.
A number of people expressed interest in participating in Anne's study. And one individual, Alison Williams, is already in email communication with Dr Tsanas to run a pilot version of the pilot and refine aspects of it.
Year(s) Of Engagement Activity 2019
URL https://www.edinburghparkinsons.org/research-interest-group/
 
Description Parkinson's UK Edinburgh Research Interest Group 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Supporters
Results and Impact Hosting of an installment of the ERIG presented by Dr. Maria Doitsidou. Her talk sparked lots of discussion and questions afterwards.

Dr Doitsidou and I are now in discussions about two collaborative grant applications to be submitted in 2016. The first is a Wellcome Trust Seed award, and the second for an MRC NMHB project grant, with Dr. Doitsidou as lead PI for both applications.
Year(s) Of Engagement Activity 2015
 
Description Parkinson's UK branch visit - Aberdeen 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Participants in your research and patient groups
Results and Impact On 13th April, 2011 I visited the Aberdeen branch of Parkinson's UK to present my research.

Stimulating discussions and positive feedback.
Year(s) Of Engagement Activity 2011
 
Description Parkinson's UK branch visit - Edinburgh 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Participants in your research and patient groups
Results and Impact On 11th April I gave a presentation of my research in Edinburgh, and my host was Dr. Patrick Mark. Patients, family and carers were in attendance and my post-doctoral fellow Dr. Fatima Cavaleri joined me.

I had a very enthusiastic reception and excellent feedback, and they donated £110,474 to Parkinson's UK towards my project (F-0902).
Year(s) Of Engagement Activity 2012
 
Description Parkinson's UK branch visit - Falkirk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact On 16th September, 2014 I spoke to over 50 people with Parkinson's and their families about the latest research in my lab funded by Parkinson's UK, the Cure Parkinson's Trust, and the MRC. A considerable amount of questions were asked after my talk, and later one-to-one.

The organisers informed me they were very pleased with my talk, and will continue to raise funds towards my project.
Year(s) Of Engagement Activity 2014
 
Description Parkinson's UK branch visit - Inverness 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Participants in your research and patient groups
Results and Impact On 3rd September, 2011 I traveled to Inverness to present my research to the Inverness Young Parkinson's group.

Very positive feedback and discussions.
Year(s) Of Engagement Activity 2011
 
Description Parkinson's UK branch visit - North Glasgow 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Participants in your research and patient groups
Results and Impact On 11th January, 2012 I traveled to Glasgow and gave a presentation to the North Glasgow Branch and representatives of the Glasgow Free Masons.

My talk was very well received and was linked to a donation of £28,700 from the Glasgow Free Masons and £4000 from the North Glasgow branch to Parkinson's UK towards my project (F-0902).
Year(s) Of Engagement Activity 2012
 
Description Parkinsons UK branch visit - Stewartry Support Group 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact On 14th April, 2012 I traveled to Castle Douglas, Scotland to give a presentation about my research and meet Parkinson's patients and their families. About 30 people were in attendance.

Feedback from my presentation was very positive, and they donated £2,000 to Parkinson's UK in November 2012 towards my project (F-0902).
Year(s) Of Engagement Activity 2012
 
Description Presentation at Parkinson's UK Reseach Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact The talk was presented by Dr. Maurice Canham, the post-doctoral lead on the human embryonic stem cell (hESC) transplantation project. Discussion was generated around the unique position of the UK because of the large number of clinical-grade hESC lines available.

A notable impact was discussion with Matthew Durdy, the Chief Business Officier for Cell Therapy Catapult. We have initiated discussions around cryopreservation of cells for clinical translation, and we plan to work together on this project
Year(s) Of Engagement Activity 2014
URL http://www.parkinsons.org.uk/content/parkinsons-uk-research-conference
 
Description Roslin Institute Seminar 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact I presented a seminar of my current research to 50-60 basic and veterinary scientists on 20th November, 2013 at The Roslin Institute.

I had very stimulating discussions after my seminar, including an excellent experimental suggestion from a PhD student. I am now implementing the idea into one of my projects.
Year(s) Of Engagement Activity 2013
 
Description Scottish Parliament 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Type Of Presentation Poster Presentation
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact 16 MSPs attended including the Public Health Minister for Scotland. Other Parkinson's researchers and patients and carers also attended.

I made a connection with a scientist in Dundee that will lead to a visit from one of his new recruits to my lab. I also discussed with a clinican scientist in Glasgow about accessing his patient cohorts for a new biomarker study in my lab.
Year(s) Of Engagement Activity 2013
 
Description The Stem Cell Podcast Ep. 59 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Participants in your research and patient groups
Results and Impact On 4th December, 2015 I discussed the issue of clinical-grade human embryonic stem cells (hESCs) for therapeutic applications for Parkinson's with The Stem Cell Podcast hosts Dr Christopher Fasano and Dr Yosif Ganat. This is in relation to our recently published paper in Scientific Reports entitled "The molecular karyotype of 25 clinical-grade hESC lines."
The podcast went live on 8th December, 2015 and I subsequently received emails from researchers complimenting me on the discussing, including from the Pasteur Institute.

On 24th December, I received an email from Shaun Teacher regarding The Stem Cell Podcast, which he listened to. He works for BioTime, Inc, a California-based company that has the commerical rights for clinical-grade human embryonic stem cell (hESC) lines established by Jeremy Crook in Singapore. We are in discussions now about how my academic work and their commercial work can work together to bring these cell lines into industrial us in the United States.
Year(s) Of Engagement Activity 2015
URL http://stemcellpodcast.com/ep-59-clinical-grade-featuring-dr-tilo-kunath
 
Description Tsukuba PhD week 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Type Of Presentation Workshop Facilitator
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact I hosted 10 PhD student from the University of Tsukuba, Japan during the week of 16th-20th September, 2013. This was called the Edinubrgh-Tsukuba Summer School. Organised presentations of the PhD students and also members of MRC CRM and from other parts of the University of Edinburgh.

A notable and unexpected result of this hosting was an offer from the University of Tsukuba to generate a genetically mutant mouse of my mice free-of-charge.I have provided them with details to make a Parkinson's model, and they will have made the animals in late 2013, and they will ship mutant sperm to us in March 2014.
Year(s) Of Engagement Activity 2013
 
Description University of Toronto Symposium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation keynote/invited speaker
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact On 10th April I presented a lecture at the 20th Anniversary Symposium of the Collaborative Program in Developmental Biology at the University of Toronto.

Not aware of any impact.
Year(s) Of Engagement Activity 2015
URL http://www.moleculargenetics.utoronto.ca/announcements/2015/7/29/cpdb-20th-anniversary-symposium
 
Description WPC 2013 Montreal Workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Local
Primary Audience Participants in your research and patient groups
Results and Impact On 30th November, 2013 the Edinburgh Branch of Parkinson's UK hosted a workshop to present and discuss what happened at the World Parkinson's Congress in Montreal (1-4 October, 2014). A post-doc in my lab, Dr. Fella Hammachi, presented a summary of several talks she attended at this conference.

The reception from Fella's presentation was overwhelmingly positive. An email I received from Ken Bowler dated 30th Nov, 2013 stated "I am writing to you to express our sincere thanks to you for arranging for Fella to speak at the Symposium today. She was really excellent and that view seems to be pretty widespread. For me, she hit exactly the right level."
Year(s) Of Engagement Activity 2013
URL http://www.edinburghparkinsons.org/wpc-symposium/
 
Description West Lothian Parkinson's UK site visit 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Supporters
Results and Impact On 24th June I hosted a site visit the my laboratory at the MRC Centre for Regenerative Medicine for the West Lothian branch of Parkinson's UK. It consisted of a talk and discussion about my research followed by a tour of the facilities.

There was lots of discussion on the day and they have donated funds to Parkinson's UK on behalf of my project.
Year(s) Of Engagement Activity 2015