Canada Partnering Award: Revealing the biological and molecular functions of organelle contacts in mammalian cells
Lead Research Organisation:
UNIVERSITY OF EXETER
Department Name: Biosciences
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Publications
Carmichael R
(2023)
Organelle Membrane Extensions in Mammalian Cells
in Biology
Costello JL
(2023)
Differential roles for ACBD4 and ACBD5 in peroxisome-ER interactions and lipid metabolism.
in The Journal of biological chemistry
Kors S
(2022)
VAP Proteins - From Organelle Tethers to Pathogenic Host Interactors and Their Role in Neuronal Disease.
in Frontiers in cell and developmental biology
Kors S
(2022)
Multiple Ways to Keep FFAT Under Control!
in Contact (Thousand Oaks (Ventura County, Calif.))
Kors S
(2022)
Controlling contacts-Molecular mechanisms to regulate organelle membrane tethering.
in BioEssays : news and reviews in molecular, cellular and developmental biology
Kumar R
(2024)
The peroxisome: an update on mysteries 3.0
in Histochemistry and Cell Biology
Linke V
(2025)
Integrated proteome and lipidome analyses place OCIAD1 at mitochondria-peroxisome intersection balancing lipid metabolism.
in Journal of cell science
| Description | Peroxisomes (PO) are multifunctional organelles with pivotal cooperative roles in cellular lipid metabolism, redox balance, signalling, and combat of infectious diseases. Essential functional cooperation between specialized organelles is often mediated through inter-organellar membrane contacts. Disruption of organelle contacts has been linked to disease whereas their formation may support the combat of infectious diseases, cellular stress or adaptation of metabolic functions to cellular needs. Therefore, revealing the molecular composition of contact sites, and understanding when contacts are formed, how they are regulated and how they can be modulated, has high potential to contribute to therapeutic approaches for the treatment of pathological conditions associated with neurodegeneration, cellular ageing, infection and impaired lipid homeostasis. Key findings: Our partnership award allowed us to employ a state-of-the art proximity proteomic mass spectrometry assay (Bio-ID) which has been developed by our partner. We successfully use this technology to identify novel binding partners for the novel tether proteins ACBD5/4, which are involved in membrane contact site formation between peroxisomes and the endoplasmic reticulum (ER). The approach revealed novel interaction partners, which are currently verified and characterised. As loss of ACBD5 results in human disease with neurological abnormalities, our findings will be of great importance for the characterisation of ACBD5 function, its pathophysiology and diagnostic approaches. Our approach revealed several lipid binding proteins, and their role in membrane lipid transfer from the ER to peroxisomes was investigated using cellular model systems. Our studies revealed a role for VPS13 proteins in membrane expansion of peroxisomes, which is an important pre-requisite for the multiplication of peroxisomes through membrane growth and division. Our findings shed new light on fundamental mechanisms involved in the formation/biogenesis of peroxisomes. Defects in peroxisome biogenesis result in severe disorders with limited treatment options. A manuscript with our findings is in preparation. In a cooperative approach, we identified the first tether proteins which link peroxisomes to mitochondria. We revealed that, under conditions of mitochondrial oxidative stress, these organelle contacts increase to protect mitochondria from oxidative stress (manuscript submitted). |
| Exploitation Route | Understanding how organelle contacts are formed and regulated, and how they can be modulated, has high potential to contribute to therapeutic approaches for the treatment of pathological conditions associated with impaired lipid and/or redox homeostasis, a hallmark of cellular ageing/age-related disorders including neurodegeneration, which present a major socio-economic burden globally. In addition, we are generating valuable protein-interaction data/depositories with relevance for the scientific community. |
| Sectors | Communities and Social Services/Policy Education Healthcare Pharmaceuticals and Medical Biotechnology |
| Description | Our findings have contributed to characterisation and better understanding of organelle-based/peroxisomal disorders. They revealed the molecular reason for disease and are thus included in the diagnostics of peroxisome-based disorders. We have established close links to the Global Foundation for Peroxisomal Disorders (GFPD), which supports patients and carers dealing with peroxisomal disorders worldwide, in addition to our links to Zellweger UK, a charity supporting patients and carers dealing with peroxisomal disorders in the UK and Ireland, and support their activities. Our findings are also included in education activities to inform the public about modern cell biological/biomedical, discovery-based research and the fundamental rules of life. |
| First Year Of Impact | 2022 |
| Sector | Communities and Social Services/Policy,Education,Healthcare |
| Impact Types | Societal |
| Description | IB syllabus |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Contribution to new or Improved professional practice |
| Description | Understanding the molecular mechanisms of organelle communication in the regulation of cellular lipid metabolism and developmental processes |
| Amount | £638,000 (GBP) |
| Funding ID | BB/W015420/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2022 |
| End | 09/2025 |
| Description | Organelle contacts and oxidative stress |
| Organisation | University of Leuven |
| Country | Belgium |
| Sector | Academic/University |
| PI Contribution | Analysis of the impact of oxidative stress on membrane contacts sites/organelle cooperation in human cells using molecular cell biology and ultrastructural studies/quantitative EM. |
| Collaborator Contribution | The partner generated samples using a sophisticated cell model generated by the partner, which allows generation of H202/oxidative stress in different cellular compartments. |
| Impact | The collaboration generated data for publication and upcoming grant proposals. It contributed to skills training and closer cooperation with the partner. This is a multi-disciplinary cooperation which combines biochemical and cell biological/ultrastructural approaches. |
| Start Year | 2021 |
| Description | Biosciences Research Conference |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Professional Practitioners |
| Results and Impact | Our research team participated in the Biosciences Research Conference (17-18 June 2024) at the University. The conference brought together the diverse and dynamic research that is performed in the Biosciences department. BBSRC-funded researchers were selected for an oral presentation and talked about the ongoing research in our lab or presented posters. A BBSRC-funded PDRA from our team was also a member of the organising committee. Our team (including technicians) participated in a plenary discussion on research culture and recently established research themes. This sparked questions and discussions afterwards, informed others about our BBSRC-funded research and resulted in requests for more information or collaboration. It supported networking activities and contributed to the skills training of the BBSRC-funded team members (e.g., organisation, oral and poster presentation, communication). |
| Year(s) Of Engagement Activity | 2024 |
| Description | Biosciences Research Conference 2022 |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Professional Practitioners |
| Results and Impact | Our research team participated in the Biosciences Research Conference (28-29 June 20220 at the University. The conference brought together the diverse and dynamic research that is done in the Biosciences department. BBSRC-funded researchers were selected for an oral presentation and talked about the ongoing research in our lab or presented posters. A BBSRC-funded PDRA from our team was also a member of the organising committee. This sparked questions and discussions afterwards, informed others about our BBSRC-funded research and resulted in requests for more information or collaboration. It supported networking activities and contributed to the skills training of the BBSRC-funded team members (e.g., organisation, oral and poster presentation, communication). |
| Year(s) Of Engagement Activity | 2022 |
| Description | OEPM2024 |
| 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 co-organised an international scientific meeting with focus on peroxisomes, the 9th Open European Peroxisome Meeting 2024. This bi-annual meeting aims to give young researchers the opportunity to present their work to an international audience. Therefore, all talks are presented exclusively by early-stage researchers. This sparked questions and discussions throughout the meeting, resulted in new research cooperations, networking, internationalisation and integration/recognition of PhD students, postdocs and research technicians. |
| Year(s) Of Engagement Activity | 2024 |
| URL | https://www.oepm2024.com/ |
| Description | Press Release - regulation of organelle contact |
| 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 | Public/other audiences |
| Results and Impact | Press release to inform and increase awareness of new discoveries in molecular cell biology with link to biomedicine/human disease with respect to the regulation of organelle contacts and organelle cooperation. Our study has shed new light on how organelle contacts are regulated at the molecular level. It sparked questions and discussions, increased awareness and interest. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.exeter.ac.uk/research/news/articles/newdiscoveryonregulationo.html |
| Description | Public outreach article 2023 |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | We published an outreach article to inform the public about organelle-based disorders with impact on lipid metabolisma nd neurodegeneration. This was part of our cooperation with the charity Zellweger UK, which supports patients and families with organelle (peroxisome)-based genetic disorders. This increased public interest in our research on organelle function and in our research group, sparked questions and discussions, and informed the public about organelle -based disorders and their link to lipid metabolism and neuropathology. |
| Year(s) Of Engagement Activity | 2023 |
| URL | https://www.openaccessgovernment.org/article/peroxisomes-lipids-and-neurodegeneration-disease/155843... |
| Description | Teaching award event |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Professional Practitioners |
| Results and Impact | Student Guild teaching award event - the PI was shortlisted for a teaching award for inspirational teaching and invited to an award event - reason for shortlisting/recognition was inclusion of BBSRC-funded research in education/teaching which inspired UG students in modules |
| Year(s) Of Engagement Activity | 2024 |
| Description | University of Bielefeld |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Undergraduate students |
| Results and Impact | Approx. 50-100 UG/PG students attended a presentation (invited speaker) on Organelle Cooperation in Health and Disease, which sparked questions and discussions afterwards and supported decision making. |
| Year(s) Of Engagement Activity | 2023 |
| Description | University of Toronto, CAN |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Approx. 40-50 researchers attended a presentation (invited speaker) on Organelle Interplay and Dynamics in human Health and Disease, which sparked questions and discussions afterwards and supported decision making. A research cooperation was strengthened, data discussed and plans made for further activities. |
| Year(s) Of Engagement Activity | 2023 |
| Description | University of Washington, Seattle, USA |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Approx. 100 researchers attended a presentation on organelle interplay and membrane dynamics in health and disease at a conference for principal investigators to discuss the advancements and future developments in organelle/peroxisome research. This sparked questions and discussions throughout the meeting and resulted in new research cooperations/grant proposal submission. In addition, a workshop with patients, practitioners and researchers sparked discussions and questions and efforts to tackle peroxisomal disorders. |
| Year(s) Of Engagement Activity | 2023 |
| Description | Zellweger Charity Event 2022 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Undergraduate students |
| Results and Impact | A member of the Zellweger UK charity and parent/carer of a Zellweger patient informed UG/PG students and academic staff about the work and aims of the ZUK charity and the day-to-day life with a Zellweger patient. This patient-centred online session complemented learning activities on the underlying biological science and diagnostics. The session was very well received and sparked questions and discussions afterwards. It greatly increased awareness of organelle/peroxisome-based disorders and our BBSRC funded research. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.zellweger.org.uk/ |
| Description | Zellweger Charity Event 2023 |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Undergraduate students |
| Results and Impact | A member of the Zellweger UK charity and parent/carer of a Zellweger patient informed UG/PG students and academic staff about the work and aims of the ZUK charity and the day-to-day life with a Zellweger patient. This patient-centred online session complemented learning activities on the underlying biological science and diagnostics. The session was very well received and sparked questions and discussions afterwards. It greatly increased awareness of organelle/peroxisome-based disorders and our BBSRC funded research. |
| Year(s) Of Engagement Activity | 2023 |
| URL | https://www.zellweger.org.uk/ |
| Description | Zellweger Charity Event 2024 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Undergraduate students |
| Results and Impact | A member of the Zellweger UK charity and parent/carer of a Zellweger patient informed UG/PG students and academic staff about the work and aims of the ZUK charity and the day-to-day life with a Zellweger patient. This patient-centred online session complemented learning activities on the underlying biological science and diagnostics. The session was very well received and sparked questions and discussions afterwards. It greatly increased awareness of organelle/peroxisome-based disorders and our BBSRC funded research. |
| Year(s) Of Engagement Activity | 2024 |
| URL | https://www.zellweger.org.uk/ |
| Description | work experience placement 2024 (school) |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Schools |
| Results and Impact | A student from a regional school performed a work experience in my research group. The student really enjoyed the project and engaged with UG and PG students at University as well as with academics. The internship contributed to the skills training of the student, who is interested in Biosciences/Medical Biosciences and will support his UK University application. It also informed about our BBSRC funded research in organelle biology and disease. |
| Year(s) Of Engagement Activity | 2024 |