Alpha-synuclein and its interplay with metals in Parkinson's disease 1=Chemical reaction dynamics and mechanisms 2=Healthcare technologies
Lead Research Organisation:
University of Warwick
Department Name: Sch of Engineering
Abstract
This project will extend and apply recent analytical advances in the characterization of transition metals and peptides in-vitro and in human tissue, to advance understanding of Parkinson's disease pathology [Everett et al, Nanoscale, 2018; Lermyte et al, Cells, 2019, Brooks et al, Angewandte Chemie, 2020]. The project builds directly on Bellingeri's findings in her MChem final year project work in 2018/19 [Lermyte et al, Cells 2019 and conference presentations at ASMS 2019 and BMSS 2019], and will involve collaboration between the Trace Metals in Medicine Laboratory in the School of Engineering, Warwick Chemistry, Keele University, and proposed experimental work at the Diamond Light Source synchrotron. The specific aim of this project is to determine the properties of the aggregating protein a-synuclein, especially its metal binding properties, in-vitro and where it forms aggregates in the human brain. This work will address key gaps in current understanding of the role of this protein central to Parkinson's disease pathology, provide new information about the contrast in magnetic resonance imaging arises from these aggregates, and inform therapeutic strategies with metal chelating drugs currently in clinical trials. REFERENCES [Brooks 2020] J. Brooks, J. Everett, F. Lermyte, V. Tjendana Tjhin, S. Banerjee, P.J. Sadler, P.B. O'Connor, C. Morris, N. Telling and J.F. Collingwood, Label-Free Nanoimaging of Neuromelanin in the Brain by Soft X-ray Spectromicroscopy. Angewandte Chemie International Edition. 2020 May 14; 59(29):11984-11991. [Lermyte 2019] Frederik Lermyte, James Everett, Jake Brooks, Francesca Bellingeri, Kharmen Billimoria, Peter J. Sadler, Peter B. O'Connor, Neil D. Telling, Joanna Collingwood, 'Emerging approaches to investigate the influence of transition metals in the proteinopathies', Cells 2019 Oct 10;8(10)PubMed PMID: 31658742; [Everett 2018] James Everett, Joanna F. Collingwood [corresponding author], Vindy Tjendana-Tjhin, Jake Brooks, Frederik Lermyte, Germán Plascencia-Villa, Ian Hands-Portman, Jon Dobson, George Perry and Neil D. Telling, 'Nanoscale synchrotron X-ray speciation of ferrous iron and calcium compounds in amyloid plaque cores from Alzheimer's disease subjects', Nanoscale, 2018 v10, p11782-11796, https://doi.org/10.1039/C7NR06794A
Organisations
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| EP/T51794X/1 | 01/10/2020 | 30/09/2025 | |||
| 2401573 | Studentship | EP/T51794X/1 | 05/10/2020 | 30/09/2024 | Francesca BELLINGERI |
| Description | 41st BMSS Annual Meeting, 2021, Sheffield, UK |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Postgraduate students |
| Results and Impact | Oral presentation entitled "Human islet amyloid polypeptide (hIAPP) and and metal: an investigation into the effect of metal binding on aggregation of the hIAPP protein", involving multiple engagements with other researchers and discussion of questions. |
| Year(s) Of Engagement Activity | 2021 |
| Description | 42nd BMSS Annual Meeting, 2022, Manchester, UK |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Postgraduate students |
| Results and Impact | Oral presentation entitled " Aggregation of Human islet amyloid polypeptide (hIAPP): an investigation into the effect of metal binding on early-stage oligomerisation" to attendees of the annual British Mass Spectrometry Society including discussions surrounding the research topic |
| Year(s) Of Engagement Activity | 2022 |
| Description | ASMS Annual Conference on Mass Spectrometry and Allied Topics, 2022, Minneapolis, USA |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | Poster presentation entitled "Aggregation of Human islet amyloid polypeptide (hIAPP): an investigation into the effect of metal binding on early-stage oligomerisation" given to large international audience over multiple days. Discussions and questions were continuous throughout the time at this conference and lots of new research connections made. |
| Year(s) Of Engagement Activity | 2022 |
| Description | European Fourier Transform Mass Spectrometry Workshop, 2022, Lisbon, Portugal |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | Oral presentation entitled "Our Metal Brain: Amyloid protein aggregation and metal binding" given at an international conference with attendees from around the world. After the oral presentation there were audience questions. |
| Year(s) Of Engagement Activity | 2022 |
| Description | International Conference on Alzheimer's and Parkinson's Diseases, 2022, Barcelona, Spain |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | Oral presentation entitled "Human islet amyloid polypeptide (hIAPP) and metal binding: an investigation into amyloid protein aggregation in the presence of metal ions" given to international audience researching neurodegenerative diseases across multiple disciplines. This gave opportunity to network with others in the field and discuss new methods. |
| Year(s) Of Engagement Activity | 2022 |
| Description | International Mass Spectrometry Conference, 2022, Maastricht, Netherlands |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | Poster presentation entitled "Aggregation of Human islet amyloid polypeptide (hIAPP): an investigation into the effect of metal binding on early-stage oligomerisation" delivered to international audience over a 2 day span with multiple discussions and conversations surrounding the research |
| Year(s) Of Engagement Activity | 2022 |