CHANGE - Cellular Homeostasis And aGeing in Connective TissuE Disease (parent application EP/X031721/1)
Lead Research Organisation:
Newcastle University
Department Name: Biosciences Institute
Abstract
The increased longevity in developed countries not necessarily goes hand in hand with amelioration of health and quality of life.
Musculoskeletal, cardiovascular and neurodegenerative failure are not only hallmarks of the physical and cognitive decline in elderly
people, but also represent common traits in several early-onset hereditary connective tissue (CT) disorders. These disorders represent
a unique tool for the molecular investigation of such age-related pathologies due to the specific genetic disturbance of cellular
homeostasis. The scientific objectives of CHANGE are: (i) to investigate CT disorders to identify key pathways responsible for agerelated
decline of physiological functions, being aware of gender differences (ii) to learn more about the interdependency of these
pathways leading to stereotypic cellular responses including cellular senescence. This knowledge will pave the way for developing
innovative treatment strategies for common diseases and frailty associated with ageing. To this end, we will train and establish a
network of 10 highly-skilled early stage researchers (ESRs) equipped with scientific expertise, transferable skills and societal and
environment awareness as a foundation for their future careers. To succeed, CHANGE has built a unique and multidisciplinary
network of 7 renowned academic partners and 5 companies (including 2 non-academics as associated partners) working together to
train 10 young scientists. The ESR network will address the basic biology of ageing from an interdisciplinary perspective, by deeply
investigating CT diseases to uncover the pillars of ageing and its multi-systemic signatures. Altogether, CHANGE will provide an
integrative map of cellular/extracellular consequences of age-related changes in cartilage, bone, muscle and vasculature as
consequences to precocious disease exposure.
Musculoskeletal, cardiovascular and neurodegenerative failure are not only hallmarks of the physical and cognitive decline in elderly
people, but also represent common traits in several early-onset hereditary connective tissue (CT) disorders. These disorders represent
a unique tool for the molecular investigation of such age-related pathologies due to the specific genetic disturbance of cellular
homeostasis. The scientific objectives of CHANGE are: (i) to investigate CT disorders to identify key pathways responsible for agerelated
decline of physiological functions, being aware of gender differences (ii) to learn more about the interdependency of these
pathways leading to stereotypic cellular responses including cellular senescence. This knowledge will pave the way for developing
innovative treatment strategies for common diseases and frailty associated with ageing. To this end, we will train and establish a
network of 10 highly-skilled early stage researchers (ESRs) equipped with scientific expertise, transferable skills and societal and
environment awareness as a foundation for their future careers. To succeed, CHANGE has built a unique and multidisciplinary
network of 7 renowned academic partners and 5 companies (including 2 non-academics as associated partners) working together to
train 10 young scientists. The ESR network will address the basic biology of ageing from an interdisciplinary perspective, by deeply
investigating CT diseases to uncover the pillars of ageing and its multi-systemic signatures. Altogether, CHANGE will provide an
integrative map of cellular/extracellular consequences of age-related changes in cartilage, bone, muscle and vasculature as
consequences to precocious disease exposure.
People |
ORCID iD |
| Katarzyna Pirog (Principal Investigator) |
| Title | Black Box 3 |
| Description | Black Box is a project that originated as a collaboration between CNoS at Northumbria University (Dr Lousie Mackenzie) and Institute of Genetic Medicine at Newcastle University (Dr Katarzyna Pirog). Initially a pop-up cinema at the Institute of Genetic Medicine, sparking discussions on genetic and rare disease research, Black Box morphed into Black Box 2 which featured at the Edinburgh Science festival in 2022 and now Black Box 3, sponsored by CNoS and Northumbria University Department of Applied Sciences, a new permanent gallery space on the 4th Floor of Ellison Lab, Northumbria University. Dr Pirog is on the steering committee for the project. Converting the space of two former display cabinets into a gallery and screen-based platform, BLACK BOX3 showcases contemporary creative works at the intersection of art and science. |
| Type Of Art | Artistic/Creative Exhibition |
| Year Produced | 2023 |
| Impact | The Black Box project opened a much needed discussion between the artists and scientists and developed a creative and inclusive space for exploring and discussing ethical issues and personal experiences and perceptions of genetic and rare disease research. |
| URL | https://hosting.northumbria.ac.uk/culturalnegotiationofscience/?page_id=3000 |
| Description | Membership in the Neuromuscular disease, rare diseases and mitochondrial dysfunction theme of the NIHR BRC at Newcastle |
| Geographic Reach | Local/Municipal/Regional |
| Policy Influence Type | Influenced training of practitioners or researchers |
| URL | https://www.newcastlebrc.nihr.ac.uk/ |
| Description | Membership in the Rare Disease NUCore (Newcastle University Centre of Research Excellence) |
| Geographic Reach | National |
| Policy Influence Type | Influenced training of practitioners or researchers |
| URL | https://www.ncl.ac.uk/rare-diseases/ |
| Description | Healthy and dysplastic cell |
| Amount | £2,770 (GBP) |
| Organisation | Newcastle upon Tyne Hospitals NHS Charity |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 05/2022 |
| End | 05/2024 |
| Description | Collaboration with Dr Ana Ferreira-Duarte (Newcastle University) to perform mechanical testing of tissues from transgenic mice |
| Organisation | Newcastle University |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | In this collaboration, we are providing samples of mouse tendons and ligaments, that will be characterised using the testing methods established in Dr Ferreira-Duarte laboratory. We will use these methods to establish the mechanical changes in our knock-out and knock-in tissues to establish a broader baseline of mechanical properties of ageing joints and tissues as they progress through osteoarthritis and/or healthy ageing. |
| Collaborator Contribution | Dr Ferreira-Duarte is an expert in material sciences. Her expertise in characterisation of mechanical properties of materials will be utilised in this project to detect the mechanical changes in the mouse tendons and ligaments, that may in turn impact on the osteoarthritis progression in these models. |
| Impact | This is a multidisciplinary collaboration, bringing together a material scientists (tissue engineer) and a biologist. Dr Ferreira-Duarte is an expert in material science and in testing mechanical properties of tendons and ligaments, using the tensile testing methods that Dr Ferreira-Duarte is an expert in. |
| Start Year | 2022 |
| Description | ECMage, Extracellular Matrix Ageing Network |
| Organisation | University of Liverpool |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | ECMage is a research network that will address the key priorities in extracellular matrix (ECM) ageing across the life course. The network will define key questions and address specific challenges in defining and developing suitable in vitro models to study ECM ageing across the life course. Aspects of interest will include (but are not restricted to) ECM turnover, omics analyses, genetic drivers of variability, chronobiology, inflammation and computational modelling. The proposed network will have a diverse membership in terms of career stage and expertise and aims to foster interdisciplinary collaboration through networking events and costed opportunities for pump-prime funding. Our contribution to the network is the expertise in mouse genetics and phenotyping of mouse models of musculoskeletal conditions, knowledge of mechanosensing pathways and the ways to study the impact of ECM changes on chondrocyte biology, including the 3D models of cartilage developed during our NC3Rs funded project, our DMT and JGWP funded investigation of the role of asporin in healthy musculoskeletal ageing and in osteoarthritis progression, and the investigation of musculoskeletal ageing in the animal model of SEMD-JL2 under MSCA DN CHANGE. |
| Collaborator Contribution | The ECMage research network comprises experts in the ECM turnover, omics analyses, genetic drivers of variability, chronobiology, inflammation and computational modelling, amongst others. It links scientists from Liverpool, Newcastle, Glasgow, Manchester and Nottingham Universities, all with unique expertise in ageing research. We have already detected changes in genes involved with chronobiology and ECM turnover in our models, and we will use this collaboration to further understand these and their contribution to healthy ageing using samples from our animal models as well as our tissue engineering models. |
| Impact | There are no outputs yet |
| Start Year | 2022 |
| Description | EU Horizon Europe MSCA CHANGE Doctoral Network (grant number 101072766) |
| Organisation | University of Pavia |
| Country | Italy |
| Sector | Academic/University |
| PI Contribution | CHANGE is a HORIZON-MSCA-2021-DN-01-01 led by the University of Pavia. The project officially started in September 2022. As part of the consortium activities we will be training PhD students from the consortium in 3D culture of musculoskeletal cells using our model developed in this project as one of the tools to reduce and replace the animal use in musculoskeletal research. Together with prof Michael Briggs at Newcastle University, we have been named as work package leads for WP1 Cartilage diseases in ageing, and WP6 Engagement and dissemination, and I will use these channels as well to increase the uptake of the method developed in this project. |
| Collaborator Contribution | Whilst we provide the in vitro model of developing cartilage to validate the in vivo data and implement the 3Rs, we will also send our PhD student to the University of Pavia to learn about the use of Zebrafish models to replace mouse models of developing cartilage. Moreover, one of the partners of the consortium, LifeTech (www.lifetecgroup.com) have developed an in vitro model of the osteochondral plugs that allows compression of the constructs, and will be an excellent addition to our model in terms of replacing animal use and developing new knowledge on mechanosensing in musculoskeletal tissues. |
| Impact | The official kick-off meeting for the consortium will be in April 2023. So far the collaboration resulted in the creation of the website and in recruitment of 12 doctoral candidates for the consortium. |
| Start Year | 2022 |
| Description | Research visit by Roufaida Bouchenafa (PhD student) at University of Padova |
| Organisation | University of Padova |
| Country | Italy |
| Sector | Academic/University |
| PI Contribution | Newcastle University provided the samples necessary for this collaboration. Newcastle researcher (Doctoral Candidate in the CHANGE MSCA network) harvested the tissues in Newcastle, and visited Padova for 1 month and performed the experiments in Prof Paolo Bonaldo laboratory. |
| Collaborator Contribution | University of Padova (Bonaldo lab) provided training and reagents necessary for the histological, morphological and transcriptomic analysis of the young and aged muscle phenotype in the SEMD-JL2 mice. |
| Impact | no outputs yet |
| Start Year | 2022 |
| Description | Genetics Matters - a public engagement event, February 2023 |
| 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 | Public/other audiences |
| Results and Impact | Genetics Matters is an annual event organised by K Pirog as part of the International Rare Disease Day. It is the main dissemination and engagement channel for genetic research at Newcastle University and attracts 100 participants (public, patients, patient organisations, schools) annually. During the event we discuss outputs of our work with the patients and the public. After this year's event, we have had several requests for lab visits and placements. |
| Year(s) Of Engagement Activity | 2023 |
| URL | https://www.rarediseaseday.org/event/genetics-matters/ |
| Description | Genetics Matters public and patient engagement conference as part of International Rare Disease Day 2024 |
| 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 | As part of the International Rare Disease, Dr Pirog at Newcastle University organises "Genetics Matters", a public and patient engagement event designed to raise awareness of rare diseases and rare disease research and as a platform for the rare disease community to create new links and interactions, participate in rare disease research and find support and guidance in their diagnostic journey. Genetics Matters is an annual event that each year attracts 100+ members of general public and 40+ scientists. In 2024 the event was co-organised by Newcastle University Rare Disease Centre for Research Excellence (NUCoRE), together with the NIHR BRC and the NHIP, and took place at the Great Hall of the Discovery Museum. The event was attended by 104 participants (general public, rare disease patients and university and college students) and 40 scientists, and consisted of a panel discussion on the challenges of rare disease communities in the North East which sparked a lively debate. The afternoon was filled with hands on research tables, presentations by rare disease and ageing research teams, and interesting discussion. The event was a great success with positive and enthusiastic feedback from the participants highlighting the need for a rare disease event in the North East. We also received increased interest in research participation, and requests from several local schools for more STEM activities related to rare diseases and ageing. |
| Year(s) Of Engagement Activity | 2024 |
| URL | https://www.rarediseaseday.org/event/genetics-matters-2/ |