Towards a unifying theory of Parkinson's disease: Investigation of the biochemical and genetic role of Rab GTPases

Lead Research Organisation: University of Dundee
Department Name: School of Life Sciences

Abstract

Mutations in the LRRK2 and PINK1 genes can be inherited in patients with familial forms of Parkinson's. LRRK2 and PINK1 function as a special class of enzymes known as protein kinases whose job is to label target proteins with a chemical phosphate group (in a process known as phosphorylation). Our laboratories have previously made significant advances in understanding the function of LRRK2 and PINK1 and recently identified that these enzymes target a different class of enzymes known as Rab GTPases. We now wish to better understand how LRRK2 and PINK1 controls Rabs and how mutations in these enzymes impact on Rab functioning in cells. Towards this goal we aim to identify the key Rabs controlled by LRRK2 and PINK1 and discover the molecules that Rabs bind to in order to execute downstream communications in the cell. To complement our analysis we will collaborate with genetics researchers to determine if Rabs themselves are mutated in families with Parkinson's. This project will lead to a fundamental understanding of the cellular pathways controlled by LRRK2 and PINK1 and improve our understanding of the critical pathways affected in Parkinson's.

Technical Summary

This proposal builds on our recent exciting discovery that the LRRK2 and PINK1 kinases implicated in Parkinson's, regulate the phosphorylation and activity of Rab GTPases. LRRK2 directly phosphorylates numerous Rab isoforms on a conserved Thr/Ser residue
that lies at the centre of its effector binding motif (Thr72-Rab8A), inhibiting association with known effectors GDIs and Rabin-8 that are required for Rab8A activation. Activation of PINK1 induces phosphorylation of a distinct C-terminal residue of Rab isoforms (Ser111-Rab8A) through an as yet unknown intermediate kinase, which inhibits association with Rabin-8. Our findings therefore provide an opportunity to investigate novel biological roles for LRRK2 and PINK1 and the mechanisms implicated in Parkinson's. We will identify the key Rab isoforms that are phosphorylated by LRRK2 and PINK1 in brain and iPSC derived neurons (Alessi/Muqit/Gasser-labs). We will work on
delineating how Rab phosphorylation influences downstream signalling pathways (Alessi/Muqit-labs). Finally, we will investigate whether genetic variation in Rab GTPases and their effectors and interactors are linked to Parkinson's susceptibility (Gasser-lab). The results and reagents generated in this study together with the integration of biochemical, clinical and genetic analysis will make a major contribution to the assessment of Rab phosphorylation as central mediators of neurodegeneration.

Planned Impact

Our proposal aims to determine fundamental new knowledge on the mechanisms that underlie neurodegeneration in Parkinson's disease (PD). This is of crucial importance since PD remains incurable and moreover, none of the currently available treatments influence disease progression. We wish to understand the role of a novel signal transduction pathway that we recently uncovered in which we discovered that Rab GTPases, are the downstream target of the protein kinases LRRK2 and PINK1. Both these kinases are encoded by genes that are mutated in Parkinson's highlighting the critical role of this pathway in neuronal survival. All significant discoveries in this proposal will be published in open access journals to ensure the greatest reach and impact of the work and should significantly advance knowledge in the Parkinson's field. Our proposal also employs state-of-the-art methodologies and high quality biochemical tools to study these pathways. These methodologies and tools will be extremely useful to many labs in the field for future work.

This proposal has significant potential in the development of a novel biomarker of PD. We are generating monoclonal antibodies against phosphorylated (activated) forms of Rab enzymes and will be testing their sensitivity and specificity in Parkinson's brains and patient derived cell lines. If successful these antibodies would be a significant boost for biotechnology companies developing biomarkers and could have immediate benefit to researchers conducting clinical trials of potential anti-PD therapies.

The proposal also has potential to advance new therapeutic strategies for PD, which will be of significant benefit to pharmaceutical companies. Our labs have a major advantage in engaging with the pharmaceutical industry since the MRC Protein Phosphorylation and Ubiquitylation Unit is integrated into the Division of Signal Transduction Therapy (DSTT), the largest UK academic-industry collaboration involving six of the world's largest pharmaceutical companies namely AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Janssen Pharmaceutica, Pfizer and Merck KGaA. All new data arising from my work is made available to these companies prior to publication to enable them to consider the potential of the research for drug discovery. In addition we meet with company representatives three times per year, which gives my work significant exposure and maximises the possibilities for drug discovery and development by one of these companies.

Overall we strongly believe that this proposal under our direction will lead to significant progress in understanding Parkinson's and ultimately this will lead to improvements in human health.
 
Description Assessment of LRRK2 activity in G2385R carriers
Amount £57,771 (GBP)
Organisation Michael J Fox Foundation 
Sector Charity/Non Profit
Country United States
Start 08/2018 
End 07/2019
 
Description Chemical Screen to identify PPM1H activator
Amount £306,000 (GBP)
Organisation Michael J Fox Foundation 
Sector Charity/Non Profit
Country United States
Start 11/2019 
End 12/2020
 
Description Equipment grant
Amount £260,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start  
 
Description Equipment grant
Amount £40,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start  
 
Description Equipment grant
Amount £625,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start  
 
Description Genome wide screens to uncover novel upstream regulators of LRRK2
Amount £305,944 (GBP)
Organisation Michael J Fox Foundation 
Sector Charity/Non Profit
Country United States
Start  
 
Description J MacDonald Menzies
Amount £177,000 (GBP)
Organisation J Macdonald Menzies Charitable Trust 
Sector Charity/Non Profit
Country United Kingdom
Start  
 
Description Lanston Award
Amount £17,582 (GBP)
Organisation Michael J Fox Foundation 
Sector Charity/Non Profit
Country United States
Start 01/2018 
End 12/2019
 
Description MRC Project grant
Amount £389,075 (GBP)
Organisation Network of Centres of Excellence in Neurodegeneration (COEN) 
Sector Public
Country United Kingdom
Start  
 
Description Project grant
Amount £97,000 (GBP)
Organisation Michael J Fox Foundation 
Sector Charity/Non Profit
Country United States
Start  
 
Description Project grant
Amount £122,000 (GBP)
Organisation Michael J Fox Foundation 
Sector Charity/Non Profit
Country United States
Start  
 
Description Project grant
Amount £63,000 (GBP)
Organisation Michael J Fox Foundation 
Sector Charity/Non Profit
Country United States
Start  
 
Description Project grant
Amount £23,000 (GBP)
Organisation Michael J Fox Foundation 
Sector Charity/Non Profit
Country United States
Start  
 
Description Project grant
Amount £93,000 (GBP)
Organisation Michael J Fox Foundation 
Sector Charity/Non Profit
Country United States
Start  
 
Description QQ Renewal
Amount £25,590,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start  
 
Description Rab LEAPs Renewal
Amount £332,000 (GBP)
Organisation Michael J Fox Foundation 
Sector Charity/Non Profit
Country United States
Start 08/2018 
End 07/2020
 
Description Renewal of Division of Signal Transduction Therapy Unit
Amount £7,200,000 (GBP)
Organisation Dundee Signal Transduction Therapy (DSTT) Consortium 
Sector Academic/University
Country United Kingdom
Start  
 
Description Studentship
Amount £92,000 (GBP)
Organisation Parkinson's UK 
Sector Charity/Non Profit
Country United Kingdom
Start  
 
Description Tools Development
Amount £83,244 (GBP)
Organisation Michael J Fox Foundation 
Sector Charity/Non Profit
Country United States
Start 10/2018 
End 09/2020
 
Description Tools and Animal Models
Amount £54,902 (GBP)
Organisation Michael J Fox Foundation 
Sector Charity/Non Profit
Country United States
Start 07/2018 
End 12/2019
 
Title Development of novel state of the art phospho-specific Rabbit monoclonal antibodies to studdy LRRK2 mediated phosphorylation of Rab proteins in Parkinson's disease 
Description Mutations that activate the LRRK2 (leucine-rich repeat protein kinase 2) protein kinase predispose to Parkinson's disease, suggesting that LRRK2 inhibitors might have therapeutic benefit. Our recent work has revealed that LRRK2 phosphorylates a subgroup of 14 Rab proteins, including Rab10, at a specific residue located at the centre of its effector-binding switch-II motif. In the present study, we analyse the selectivity and sensitivity of polyclonal and monoclonal phospho-specific antibodies raised against nine different LRRK2-phosphorylated Rab proteins (Rab3A/3B/3C/3D, Rab5A/5B/5C, Rab8A/8B, Rab10, Rab12, Rab29[T71], Rab29[S72], Rab35 and Rab43). We identify rabbit monoclonal phospho-specific antibodies (MJFF-pRAB10) that are exquisitely selective for LRRK2-phosphorylated Rab10, detecting endogenous phosphorylated Rab10 in all analysed cell lines and tissues, including human brain cingulate cortex. We demonstrate that the MJFF-pRAB10 antibodies can be deployed to assess enhanced Rab10 phosphorylation resulting from pathogenic (R1441C/G or G2019S) LRRK2 knock-in mutations as well as the impact of LRRK2 inhibitor treatment. We also identify rabbit monoclonal antibodies displaying broad specificity (MJFF-pRAB8) that can be utilised to assess LRRK2-controlled phosphorylation of a range of endogenous Rab proteins, including Rab8A, Rab10 and Rab35. The antibodies described in the present study will help with the assessment of LRRK2 activity and examination of which Rab proteins are phosphorylated in vivo These antibodies could also be used to assess the impact of LRRK2 inhibitors in future clinical trials. 
Type Of Material Technology assay or reagent 
Year Produced 2017 
Provided To Others? Yes  
Impact All companies and researchers investigating LRRK2 are now using our technology. A company called Denali has just launched the first clinical trials for LRRK2 inhibitors and are using our reagents for their monitoring efficacy of LRRK2 inhibitors. Many other companies are likely to follow suit 
 
Description DSTT renewal 2016 
Organisation Boehringer Ingelheim
Country Germany 
Sector Private 
PI Contribution Boehringer-Ingelheim, GlaxoSmithKline and Merck-Serono - each company pays £600000 per annum over the four year period. The aim of the collaboration is to help the pharmaceutical companies accelerate the development of drugs that inhibit protein and lipid kinases and phosphatases with therapeutic potential for the treatment of disease.
Collaborator Contribution The MRC-PPU benefits in many ways as a result of the DSTT research collaboration.
Impact uring the collaboration, the Unit has helped to launch and/or accelerate many drug discovery programmes, some of which have entered human clinical trials. The collaboration led the Unit to develop the technology of protein kinase profiling which has developed into an industry worth over £100 million per annum. It also led to the creation of the European Division of Upstate Incorporated in Dundee which currently employs about 50 people. The Unit's first publication on protein kinase profiling was named in 2009 by the Institute for Scientific Information, Philadelphia as Europe's most cited paper in the field of Cel Biology from 1996-2007, with over 2,200 citations. During the collaboration, the Unit has filed 36 patents and 30 licenses have been taken up by the pharmaceutical industry. The DSTT is widely regarded as a model of how academia and industry should interact for which it received a Queen's Anniversary Award for Higher Education which was presented by the Queen and Duke of Edinburgh at Buckingham Palace in February 2006. GlaxoSmithKline have announced that their BRAF protein kinase inhibitor Dabrafenib (Tafinlar), has been approved by both the European Commission and the United States Food and Drug Administration for the treatment of unresectable or metastatic melanoma associated with the BRAF V600E mutation. Unresectable melanoma is that which cannot be removed by surgery, while metastatic melanoma is that which has spread to other parts of the body. The new drug was developed employing BRAF enzymes generated by researchers in the Division of Signal Transduction Therapy (DSTT) in the College of Life Sciences at Dundee.
Start Year 2016
 
Description DSTT renewal 2016 
Organisation GlaxoSmithKline (GSK)
Country Global 
Sector Private 
PI Contribution Boehringer-Ingelheim, GlaxoSmithKline and Merck-Serono - each company pays £600000 per annum over the four year period. The aim of the collaboration is to help the pharmaceutical companies accelerate the development of drugs that inhibit protein and lipid kinases and phosphatases with therapeutic potential for the treatment of disease.
Collaborator Contribution The MRC-PPU benefits in many ways as a result of the DSTT research collaboration.
Impact uring the collaboration, the Unit has helped to launch and/or accelerate many drug discovery programmes, some of which have entered human clinical trials. The collaboration led the Unit to develop the technology of protein kinase profiling which has developed into an industry worth over £100 million per annum. It also led to the creation of the European Division of Upstate Incorporated in Dundee which currently employs about 50 people. The Unit's first publication on protein kinase profiling was named in 2009 by the Institute for Scientific Information, Philadelphia as Europe's most cited paper in the field of Cel Biology from 1996-2007, with over 2,200 citations. During the collaboration, the Unit has filed 36 patents and 30 licenses have been taken up by the pharmaceutical industry. The DSTT is widely regarded as a model of how academia and industry should interact for which it received a Queen's Anniversary Award for Higher Education which was presented by the Queen and Duke of Edinburgh at Buckingham Palace in February 2006. GlaxoSmithKline have announced that their BRAF protein kinase inhibitor Dabrafenib (Tafinlar), has been approved by both the European Commission and the United States Food and Drug Administration for the treatment of unresectable or metastatic melanoma associated with the BRAF V600E mutation. Unresectable melanoma is that which cannot be removed by surgery, while metastatic melanoma is that which has spread to other parts of the body. The new drug was developed employing BRAF enzymes generated by researchers in the Division of Signal Transduction Therapy (DSTT) in the College of Life Sciences at Dundee.
Start Year 2016
 
Description DSTT renewal 2016 
Organisation Merck
Department Merck Serono Ltd
Country United Kingdom 
Sector Private 
PI Contribution Boehringer-Ingelheim, GlaxoSmithKline and Merck-Serono - each company pays £600000 per annum over the four year period. The aim of the collaboration is to help the pharmaceutical companies accelerate the development of drugs that inhibit protein and lipid kinases and phosphatases with therapeutic potential for the treatment of disease.
Collaborator Contribution The MRC-PPU benefits in many ways as a result of the DSTT research collaboration.
Impact uring the collaboration, the Unit has helped to launch and/or accelerate many drug discovery programmes, some of which have entered human clinical trials. The collaboration led the Unit to develop the technology of protein kinase profiling which has developed into an industry worth over £100 million per annum. It also led to the creation of the European Division of Upstate Incorporated in Dundee which currently employs about 50 people. The Unit's first publication on protein kinase profiling was named in 2009 by the Institute for Scientific Information, Philadelphia as Europe's most cited paper in the field of Cel Biology from 1996-2007, with over 2,200 citations. During the collaboration, the Unit has filed 36 patents and 30 licenses have been taken up by the pharmaceutical industry. The DSTT is widely regarded as a model of how academia and industry should interact for which it received a Queen's Anniversary Award for Higher Education which was presented by the Queen and Duke of Edinburgh at Buckingham Palace in February 2006. GlaxoSmithKline have announced that their BRAF protein kinase inhibitor Dabrafenib (Tafinlar), has been approved by both the European Commission and the United States Food and Drug Administration for the treatment of unresectable or metastatic melanoma associated with the BRAF V600E mutation. Unresectable melanoma is that which cannot be removed by surgery, while metastatic melanoma is that which has spread to other parts of the body. The new drug was developed employing BRAF enzymes generated by researchers in the Division of Signal Transduction Therapy (DSTT) in the College of Life Sciences at Dundee.
Start Year 2016
 
Description Michael J. Fox Foundation for Parkinson's Research (MJFF) Dundee Drug Discovery Unit collaborative Chemical Screens Project Grant to identify enhancer of PPM1H 
Organisation Michael J Fox Foundation
Country United States 
Sector Charity/Non Profit 
PI Contribution We identified a new protein phosphatase termed PPM1H that our work suggests that plays a key role in counteracting LRRK2 kinase activity. Our work suggests that enhancers of PPM1H activity could therefore have therapeutic benefit for Parkinson's disease. This collaborative project enables us to undertake a screen to identify such compounds.
Collaborator Contribution MJFF have provided the funding, the Dundee Drug discovery Unit are doing the enhancer screen and my lab is providing all reagents and knowledge needed to undertake the screen and will lead with the biological effects that the identified chemical activators have
Impact We have identified some enhancer compounds that we are currently characterising
Start Year 2019
 
Description Michael J. Fox Foundation for Parkinson's Research (MJFF) Dundee Drug Discovery Unit collaborative Chemical Screens Project Grant to identify enhancer of PPM1H 
Organisation University of Dundee
Department Drug Discovery Unit
Country United Kingdom 
Sector Academic/University 
PI Contribution We identified a new protein phosphatase termed PPM1H that our work suggests that plays a key role in counteracting LRRK2 kinase activity. Our work suggests that enhancers of PPM1H activity could therefore have therapeutic benefit for Parkinson's disease. This collaborative project enables us to undertake a screen to identify such compounds.
Collaborator Contribution MJFF have provided the funding, the Dundee Drug discovery Unit are doing the enhancer screen and my lab is providing all reagents and knowledge needed to undertake the screen and will lead with the biological effects that the identified chemical activators have
Impact We have identified some enhancer compounds that we are currently characterising
Start Year 2019
 
Description Role of LRRK2 phosphorylating Rab GTPase in Parkinson's 
Organisation Max Planck Society
Department Max Planck Martinsried
Country Germany 
Sector Academic/University 
PI Contribution I was the PI of a major MJFF collaboration that lead to the discovery that LRRK2 Parkinson's kinase's phosphorylates and inhibits multiple Rab GTPases. This was very exciting as this was the first physiological substrate for LRRK2 to be identified. Our laboratory coordinated the project and laed on many of the key experiments in this project
Collaborator Contribution The group of Matthias Mann undertook all the mass spectrometer experiments in this project and Susan Pfeffer's laboratory is undertaking the cell biology analysis
Impact Grant Income that funds research of two postdoctoral researchers in my lab
Start Year 2015
 
Description Role of LRRK2 phosphorylating Rab GTPase in Parkinson's 
Organisation Stanford University
Department Department of Biochemistry
Country United States 
Sector Academic/University 
PI Contribution I was the PI of a major MJFF collaboration that lead to the discovery that LRRK2 Parkinson's kinase's phosphorylates and inhibits multiple Rab GTPases. This was very exciting as this was the first physiological substrate for LRRK2 to be identified. Our laboratory coordinated the project and laed on many of the key experiments in this project
Collaborator Contribution The group of Matthias Mann undertook all the mass spectrometer experiments in this project and Susan Pfeffer's laboratory is undertaking the cell biology analysis
Impact Grant Income that funds research of two postdoctoral researchers in my lab
Start Year 2015
 
Description 20 Year Celebration of the DSTT 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Other audiences
Results and Impact During an event at Dundee's recently opened V&A museum to celebrate the 20 year anniversary of the DSTT I gave an interview with STV news.
Year(s) Of Engagement Activity 2018
 
Description 7 2017 CDKL5 Forum Meeting - Boston, November 29-30 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Stimulate research and understanding into CDKL5 deficiency disease and stimulate new treatments to be developed
Year(s) Of Engagement Activity 2017
 
Description Attendance at the Scottish Parliament - MRC 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Policymakers/politicians
Results and Impact Myself, Professor John Rouse and Dr Paul Davies attended an event in the Scottish Parliament on 6th February to support the Medical Research Council's investment in science in Scotland and to present the work that we are doing in the MRC-PPU to MSPs.
Year(s) Of Engagement Activity 2019
 
Description Discovery may help derail Parkinson's 'runaway train 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The press release that describes the discovery of a new enzyme called PPM1H that inhibits the LRRK2 pathway. Our data suggest that is we could get enhancers of PPM1H catalytic activity this could represent a new strategy to better treat Parkinson's disease in the future
Year(s) Of Engagement Activity 2019
URL https://www.dundee.ac.uk/news/2019/discovery-may-help-derail-parkinsons-runaway-train.php
 
Description Discussion with Health reporter from Bloomberg News 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact I spend 1 hour on 8th July 2019 talking with Bloomberg News journalist Robert Langreth about the LRRk2 pathway and Parkinson's disease
Year(s) Of Engagement Activity 2019
 
Description Dolly scientist backs research drive to tackle Parkinson's disease - University of Dundee Press release 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact Professor Sir Ian Wilmut - who led the team that created Dolly the sheep - has backed an initiative to tackle Parkinson's disease, after being diagnosed with the condition.

The eminent scientist announced his diagnosis today - World Parkinson's Day - ahead of the launch of a major research programme that will see experts at the Universities of Edinburgh and Dundee join forces in the quest to better understand the disease. They will set up infrastructure to enable the first trials in Scotland in a generation for therapies that aim to slow down Parkinson's disease progression.

The new Dundee-Edinburgh Parkinson's Research Initiative aims to probe the causes of disease and translate scientific discoveries into new therapies. The ultimate goal is to find new approaches to predict and prevent Parkinson's, and to facilitate clinical testing of therapies aimed at slowing or reversing disease progression.

Professor Dario Alessi, of the University of Dundee, said, "All attempts to slow the progression of Parkinson's have thus far failed. Surprisingly today's most widely utilised Parkinson's drug levodopa was first used in the clinic in 1967.

"In recent years, our knowledge of the genetics and biology underlining Parkinson's disease has exploded. I feel optimistic and it is not unrealistic that with a coordinated research effort, major strides towards better treating Parkinson's disease can be made."

Parkinson's disease is a progressive condition caused by damage to specific cells in the brain. It affects movement and is often associated with involuntary shaking. Therapies that reduce symptoms can help to prolong quality of life, but currently there are no treatments to slow or halt the progression of the disease.

At present, Scottish patients seeking to take part in clinical trials of treatments that could delay disease progression are required to travel to centres in England or Wales, or even abroad.

Professor Wilmut said, "Initiatives of this kind are very effective not only because they bring more people together, but because they will include people with different experience and expertise. It was from such a rich seedbed that Dolly developed and we can hope for similar benefits in this project."

Dolly the sheep was created at The Roslin Institute in 1996 by a multidisciplinary research team led by Professor Wilmut. She was the first clone of an animal from an adult cell and her birth turned scientific thinking on its head.

It showed that cells from anywhere in the body could be made to behave like a newly fertilised egg - something that scientists had thought was impossible.

This breakthrough paved the way for others to develop a method of using adult cells to produce reprogrammable cells that could develop into any kind of tissue in the body - so called induced pluripotent stem cells, or iPSCs.

These cells hold great promise as therapies because of their potential to repair damaged tissues. The first clinical trials of iPSCs for Parkinson's disease are to begin in Japan later this year.

Dr Tilo Kunath, of Edinburgh's Medical Research Council Centre for Regenerative Medicine, said, "People with Parkinson's urgently require access to earlier and more accurate diagnosis, better prediction of how their disease will progress, and most importantly, the opportunity to participate in clinical trials of new treatments. This new research partnership aims to make these hopes a reality for people in Scotland."

There are more than 12,000 people living with Parkinson's disease in Scotland. Across the UK, the number is expect to double in the next 50 years as the population grows and people live longer.

The Dundee-Edinburgh Parkinson's Research Initiative will be formally launched at a public event at the Royal College of Physicians of Edinburgh on Friday 13 April.
Year(s) Of Engagement Activity 2018
 
Description Dundee Research Interest Group (DRIG) 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Patients, carers and/or patient groups
Results and Impact Myself and several members of my lab, including Dr Esther Sammler and Dr Paul Davies participated in a Parkinson's patients event organised by the Dundee Research Interest Group (DRIG) within the SLS on 18th January 2019.
Year(s) Of Engagement Activity 2019
 
Description Edinburgh Parkinson's seminar that was delivered by Giovanni Mallucci 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact PRC PPU Unit co-sponsored the Edinburgh Parkinson's seminar that was delivered by Giovanni Mallucci in which 300 patients and family members attended. Professor Dario Alessi gave the vote of thanks at the end of the seminar.
Year(s) Of Engagement Activity 2018
 
Description Interview to discuss LRRK2 and Parkinson's Disease 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Interview with "Tomorrow Edition" to discuss Parkinson's disease and LRRK2.
Year(s) Of Engagement Activity 2018
URL https://tmrwedition.com/2018/09/18/interview-with-biochemist-and-lrrk2-expert-prof-dario-alessi/
 
Description MRC Festical of Medical Research Inside Out Science Open Day 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact MRC Festival of Medical Research Inside Out Science Open day involved researchers from the MRC Protein Phosphorylation and Ubiquitylation Unit (MRC PPU) and MRC Doctoral Training Programme students (from the Schools of Life Sciences and Medicine at the University of Dundee). The MRC Festival aimed to inform, inspire and stimulate thinking about medical research. Our event was held within the School of Life Sciences and involved seven table top engagement activities, five ten-minute accessible science talks given by PhD students and early career researchers, three lab tours and three videos about the scientific work of the Unit on loop with visitors. There were two new activities called Chromatography and Stem Cell Game trialled that were developed by MRC PPU staff and students plus previously developed activities. Prior to the open day event, a primary six class at Glebelands Primary School attended a 90 minute session to give valuable feedback on talks and new activities.

Members from my lab who participated were;
Elena Purlyte - PhD Student
Alexia Kalogeropoulou - PhD Student
Jordana Freemantle - PhD Student

Overall, 129 members of public (generally family groups) were reached with 103 people visiting on the day, a further 24 Primary Six pupils and their two teachers who gave feedback on the new talks and activities ahead of the event.
The event met a number of the objectives and key messages from the 2018 - 2023 MRC Protein phosphorylation and ubiquitination Public Engagement and Communications Plan which were:

Communications Objectives
1) Generate interest in science as a career path for young people in Dundee to reveal opportunities and make science accessible.
2) Share the unit's research expertise with non-scientific communities to raise awareness of the importance of basic research in understanding health and disease.

Key Messages
1) Basic research is vital - before we can develop new medicines we first need to understand how the body works in health and disease.
2) MRC PPU is an outstanding environment to pursue phosphorylation or ubiquitylation research.
3) As scientists we value new ideas and are open to sharing our work with all who have an interest in it.

Feedback
The visitors to the event were a mixture of ages which included family groups (children under 16 years) and adults up to 70 years of age. Feedback indicated that they enjoyed themselves overall and said they would come to a similar event again. Highlights included a game developed on the topic of Stem Cells and the laboratory tours. Around a third of visitors polled had not attended a University of Dundee event before indicating we were reaching new audiences.
The talks in particular stimulated a number of questions from the audience such as:
• How long does it take for a cell to divide?
• What would happen if you lost all your amino acids?
• Is it only older people who get Parkinson's?
• What is it about not being obese that helps protect you from Alzheimer's?
• What does wildtype mean?

Participants reported having a positive experience, they all said they'd do it again and that they'd recommend a colleague take part too.
Year(s) Of Engagement Activity 2016,2018
 
Description Meeting with Juvenescence Ltd & AI - California Life Sciences company 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I met with Charles Roberts, the Chief Data Science Advisor of the Juvenescence Ltd & AI a California Life Science company. He is an entrepreneur who has founded numerous companies. I told him about our Units research and he was particularly interested in the work we are doing on Parkinson's disease
Year(s) Of Engagement Activity 2019
 
Description Parkinson's Patient/Parkinson's Uk organised event 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Gave a talk on LRRK2 in Parkinson's at a Parkinson's Patient/Parkinson's Uk organised event.
Year(s) Of Engagement Activity 2018
 
Description Parkinson's UK Supporters Event 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Discussing mine and the units research and projects to Parkinson's supporters at the Parkinson's UK Supporters Event on 2nd July 2018
Year(s) Of Engagement Activity 2018
 
Description Parkinsons Fund-raisoing 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact On Wedensday 30th November I spent 1 hour talking with James Moreland and Romualda Zabityte who work for the Enotrac company about our research on LRRK2 and Parkinson's disease. Colleagues of James Moreland have undertaken a cycling race from lands end to john ogroats to raise over £5000 for our LRRK2 research. there efforts are recorded on this blog
Year(s) Of Engagement Activity 2019
URL https://www.enotrac.com/en/news/meldungen/ENOTRAC-completed-a-1000-miles-cycle-journey-across-the-UK...
 
Description Patient visit and generous donation by Kiltwalk fundraiser Moira Cardosi towards Parkinson's disease research 
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 Patients, carers and/or patient groups
Results and Impact Moira Cardosi, Barbara Lynch and Liz Haughey visited the MRC Protein Phosphorylation Unit to meet with myself and other members of the team to hear about our exciting research into Parkinson's disease. They also presented us with a cheque in excess of £3,000 - funds that Moira Cardosi had raised during the 2019 Kiltwalk in memory of Mrs Lynch's late husband who had suffered from the condition. During a tour of the MRC PPU laboratory our visitors also gained a first-hand impression of our work and why we believe that better understanding the causes of Parkinson's disease will eventually lead to finding a cure.
Year(s) Of Engagement Activity 2020
URL https://www.ppu.mrc.ac.uk/news/generous-donation-kiltwalk-fundraiser-moira-cardosi-towards-parkinson...
 
Description Patient/fundraiser visit Pierre and Christine Descouts 
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 Patients, carers and/or patient groups
Results and Impact On Friday 17th January, 2020, I met with and talked to patient/fundraiser Pierre and Christine Descouts where we discussed the research in our Unit and showed them around the laboratories. Pierre and Christine Descouts (pdescouts@hotmail.co.uk) made a personal donation of £10,000 towards Parkinson's research to the unit.
Year(s) Of Engagement Activity 2020
URL https://www.ppu.mrc.ac.uk/news/generous-ps10000-donation-christine-and-pierre-descouts-towards-esthe...
 
Description Pioneer of Digital Blood Glucose Meter Technology visits MRC-PPU 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Professor Ian Shanks FRS and his daughter Dr Emma Shanks visited the MRC Protein Phosphorylation and Ubiquitylation Unit (PPU) on January 23rd to hear about the research being undertaken at the PPU. Ian Shanks is a pioneer of liquid crystal display (LCD) and adapted this to develop the first digital blood glucose sensor in the 1980s which has transformed the management of diabetes and benefitted millions of patients worldwide.

During their visit, they met with Dario Alessi and Miratul Muqit to hear about the latest research developments into better understanding Parkinson's disease and Philip Cohen who undertook seminal work in diabetes research to elucidate the function of insulin and delineate its signalling pathway. Finally they met with Mike Ferguson to hear how about the work of the Drug Discovery Unit and the university's links to industry.
Year(s) Of Engagement Activity 2020
URL https://www.ppu.mrc.ac.uk/news/pioneer-digital-blood-glucose-meter-technology-visits-mrc-ppu
 
Description Press Release regarding Parkinson's story 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact National media releases include; Daily Telegraph, Time, Daily Mail, Times and the Daly Telegraph
Year(s) Of Engagement Activity 2019
 
Description Radio interview with Tay fm 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Media (as a channel to the public)
Results and Impact Conducted a Radio interview with local station Tay FM to discuss the recent press release by University of Dundee, titled "Dolly scientist backs research drive to tackle Parkinson's disease"
Year(s) Of Engagement Activity 2018
 
Description School Visit 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Post doc in lab helps out at local secondary school, 10 days a year, in giving a Science lesson
Year(s) Of Engagement Activity 2015,2016
 
Description Solicitors Dinner - 31st October 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Industry/Business
Results and Impact Myself and members of my lab, Pawel Lis and Kerryn Berndsen, showed solicitors around our lab and discussed the research that we were doing on Parkinson's disease. I participated in a video that was made to describe our Parkinson's research and attended a dinner with the solicitors that also included people with Parkinson's to explain to them our research and why it was important.
Year(s) Of Engagement Activity 2019
 
Description The Great Scottish run - Glasgow, 10k 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact Myself and other members of the MRC PPU participated in the Glasgow 10K race as part of Marc van Grieken's "Shaky Team from Shaky Tou. This was to rais awareness of Parkinsons disease.
Year(s) Of Engagement Activity 2019
URL https://www.ppu.mrc.ac.uk/news/great-scottish-run-mrc-ppu-support-marc-van-griekens-fundraising-effo...
 
Description Visit from Annie MacLeod, Scotland Director for Parkinson's UKs 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Industry/Business
Results and Impact Annie MacLeod, Scotland Director for Parkinson's UK visit our lab on Thursday 7th March. The purpose of Annie's visit was to find out more about our research. Annie also had a tour of our labs as well as meeting with myself, Miratul Muqit and Esther Sammler.
Year(s) Of Engagement Activity 2019
 
Description Visit from the Scottish Chinese consulate to the MRC PPU 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact In December 2019 I welcomed Consul General Mr Qiang Ma, as well as Mr Wei Zen and Mr Wenbin Xiao, of the Consulate General of the People's Republic of China in Edinburgh to the MRC PPU where I gave them a tour of our unit and talked to them about the Chinese collaborations that our Unit has and the increasing number of Chinese staff working in our Unit. They also got the chance to meet with many Chinese MRC PPU researchers.
Year(s) Of Engagement Activity 2019
URL https://twitter.com/mrcppu/status/1207971823176032256