Opportunities to modulate extracellular matrix secretion and assembly for long term health
Lead Research Organisation:
University of Manchester
Department Name: School of Biological Sciences
Abstract
Collagen is the most abundant structural protein in the body, making up 1/3 of our mass. It is formed into centimetre-long fibrils. This organisation gives collagen-rich tissues their differing properties (e.g. flat plywood lattices in stretchable skin and parallel bundles in rope-like tendons). Changes to collagen underpin many of the changes we associate with ageing, such as loss of skin elasticity, poor wound healing, fibrosis, susceptibility to fracture and osteoarthritis. Most people will experience reduced quality of life due to a failure of collagen maintenance. Yet, despite its fundamental importance, we still do not fully understand how synthesis of the precursor procollagen, export from the cell, assembly and maintenance of the collagen network are regulated.
This programme brings together researchers from the Universities of Manchester and Bristol, with complementary expertise in key aspects of collagen biology. We have discovered new mechanisms of collagen secretion, shown that secretion and assembly of the collagen matrix is controlled by the circadian rhythm (the internal clocks in our tissues that cycle in response to day and night patterns of activity and light), and defined how the immune system modulates the repair of a collagen matrix on wounding. Now, we wish to exploit our multidisciplinary skills that include fundamental aspects of cell and tissue biology, integrated experiments using in vitro and in vivo models, circadian biology, mathematical modelling, and novel synthetic scaffolds to answer major questions in matrix biology. Working together, sharing tools, personnel, and expertise we will be able to make more impact than we could individually.
We have 5 specific aims:
1. Use cells and zebrafish to determine how the precursor of collagen, called procollagen, passes through the cell. We will define the role of key protein machineries in the Golgi apparatus (the central sorting station through which everything that is secreted by cells passes).
2. Understand how transport of newly-made collagen is coordinated in space and time. We will determine how the circadian rhythm regulates the formation, holding pattern, and export of collagen.
3. Derive a mathematical framework that links information on how collagen is made to how it is used in the body. This will allow us to predict how changes to any part of the pathway that makes and assembles collagen affects other components, which we can test in cells or animals.
4. Test how the collagen network responds to damage, in injury and ageing, and test how day/night rhythm and our immune system influence this. We will make minor injuries into translucent zebrafish and use fluorescently-labelled collagen to watch how cells respond and how the collagen network is rebuilt.
5. We will produce 3D scaffolds that mimic how old and young tissues perform. We know that tissues become stiffer as we age; using custom built scaffolds we can test how young cells respond to scaffolds that resemble old tissue and vice versa.
This project will also train the next generation of scientists, exposing the early-career researchers to state-of-the-art technology and equipment and to tailored training that will benefit them in their careers. Working together offers enhanced opportunities to engage with industry, clinicians and the wider public to ensure the work has the maximum impact.
As well as furthering our understanding of how the collagen matrix is assembled and regulated, the programme will generate significant new tools that will benefit the wider academic community. These include new reagents that will enable visualisation of how collagen moves through the cell, new tools to define how remodelling of collagen in skin, tendon and bone occurs during development and following injury, and new synthetic scaffolds that could be used industrially or clinically to help in repair of major skin wounds, or tendon and ligament repair following injury.
This programme brings together researchers from the Universities of Manchester and Bristol, with complementary expertise in key aspects of collagen biology. We have discovered new mechanisms of collagen secretion, shown that secretion and assembly of the collagen matrix is controlled by the circadian rhythm (the internal clocks in our tissues that cycle in response to day and night patterns of activity and light), and defined how the immune system modulates the repair of a collagen matrix on wounding. Now, we wish to exploit our multidisciplinary skills that include fundamental aspects of cell and tissue biology, integrated experiments using in vitro and in vivo models, circadian biology, mathematical modelling, and novel synthetic scaffolds to answer major questions in matrix biology. Working together, sharing tools, personnel, and expertise we will be able to make more impact than we could individually.
We have 5 specific aims:
1. Use cells and zebrafish to determine how the precursor of collagen, called procollagen, passes through the cell. We will define the role of key protein machineries in the Golgi apparatus (the central sorting station through which everything that is secreted by cells passes).
2. Understand how transport of newly-made collagen is coordinated in space and time. We will determine how the circadian rhythm regulates the formation, holding pattern, and export of collagen.
3. Derive a mathematical framework that links information on how collagen is made to how it is used in the body. This will allow us to predict how changes to any part of the pathway that makes and assembles collagen affects other components, which we can test in cells or animals.
4. Test how the collagen network responds to damage, in injury and ageing, and test how day/night rhythm and our immune system influence this. We will make minor injuries into translucent zebrafish and use fluorescently-labelled collagen to watch how cells respond and how the collagen network is rebuilt.
5. We will produce 3D scaffolds that mimic how old and young tissues perform. We know that tissues become stiffer as we age; using custom built scaffolds we can test how young cells respond to scaffolds that resemble old tissue and vice versa.
This project will also train the next generation of scientists, exposing the early-career researchers to state-of-the-art technology and equipment and to tailored training that will benefit them in their careers. Working together offers enhanced opportunities to engage with industry, clinicians and the wider public to ensure the work has the maximum impact.
As well as furthering our understanding of how the collagen matrix is assembled and regulated, the programme will generate significant new tools that will benefit the wider academic community. These include new reagents that will enable visualisation of how collagen moves through the cell, new tools to define how remodelling of collagen in skin, tendon and bone occurs during development and following injury, and new synthetic scaffolds that could be used industrially or clinically to help in repair of major skin wounds, or tendon and ligament repair following injury.
Technical Summary
Vertebrates contain 30% collagen, which occurs in the extracellular matrix mostly as fibrous networks and provides the principal supporting structures of tissues. The importance of collagen is exemplified in conditions where too little collagen leads to tissue frailty, e.g. poor wound repair and musculoskeletal diseases, which together affect 1-in-4 people in the UK. Conversely, excess collagen causes incurable fibrosis, which compromises organ function and is associated with 45% of deaths including cardiovascular disease and cancer. Effective treatments for these collagen-related conditions would have major health and socioeconomic impact.
Much of our current understanding of collagen comes from studies of the extracellular fibrils. These insoluble structures are highly ordered, contain associated components, and are centimeters in length and teradaltons in mass. Their scale and complexity make them refractory to conventional structural, molecular, and biochemical studies. Our vision is that studying newly discovered intracellular regulatory processes that control fibril formation will generate new insight into what underpins the loss of control, that contributes to so many facets of tissue pathology and disease.
To make this possible, work in our labs in Manchester and Bristol has led to technological innovations in making fluorescent collagens, imaging fibrils in wounds and at the plasma membrane, developing 3D cell culture models, and the first mathematical model of intracellular collagen trafficking. Together these will help us to test new hypotheses. We have also shown that collagen assembly is under circadian clock control. Achieving our vision relies on each member of our multidisciplinary team contributing to complementary aspects of this common research goal. We anticipate that our collective fresh approach will generate paradigm shifting discoveries that will have lasting benefit for fundamental discovery science, bioindustry and biomedicine.
Much of our current understanding of collagen comes from studies of the extracellular fibrils. These insoluble structures are highly ordered, contain associated components, and are centimeters in length and teradaltons in mass. Their scale and complexity make them refractory to conventional structural, molecular, and biochemical studies. Our vision is that studying newly discovered intracellular regulatory processes that control fibril formation will generate new insight into what underpins the loss of control, that contributes to so many facets of tissue pathology and disease.
To make this possible, work in our labs in Manchester and Bristol has led to technological innovations in making fluorescent collagens, imaging fibrils in wounds and at the plasma membrane, developing 3D cell culture models, and the first mathematical model of intracellular collagen trafficking. Together these will help us to test new hypotheses. We have also shown that collagen assembly is under circadian clock control. Achieving our vision relies on each member of our multidisciplinary team contributing to complementary aspects of this common research goal. We anticipate that our collective fresh approach will generate paradigm shifting discoveries that will have lasting benefit for fundamental discovery science, bioindustry and biomedicine.
Planned Impact
Collagen is the most abundant protein in mammalian systems and forms the primary source of tensile strength in connective tissues such as bone, cartilage, and tendons. This application seeks to address the fundamental biology of cell and tissue function by developing our understanding of the way in which cells make and shape their extracellular matrix (ECM).
Who might benefit and how?
Clinicians - Dysregulation of collagen is the hallmark of some of the most debilitating features of normal ageing and life-threatening diseases; insufficient collagen can abrogate the mechanical properties of tissues and is associated with poor wound repair (which costs the NHS £2.5 billion p.a.), as well as osteoarthritis (8 million sufferers in the UK (Versus Arthritis UK website)) and tendinopathy (1-in-4 over 40 y.o.) for which there are no effective treatments. Conversely, fibrosis - the dysregulated accumulation of collagen in place of functional tissue - is associated with 45% of all deaths (including cardiovascular disease and cancer). Progress in treating these diseases has been hindered because of poor understanding of how cells synthesise, maintain, and repair collagen-rich tissues. A deep understanding of the fundamental basic science of collagen homeostasis is an elusive cornerstone of biology. Our work could identify new targets for clinical genetics, extending to analysis of patient cohorts (such as ALSPAC) to derive new insight into onset and progression of bone and joint degeneration during ageing. Our systems to perturb and model the systems, notably in wound situations have significant potential for those working in these areas, both for acute wound treatment and in relation to fibrosis.
Industry - There is great interest in the possibility to subvert existing cellular pathways for therapeutic benefit. We have clear plans in place for direct engagement, but many others will derive value from our work in relation to engineering of cells and tissues for therapeutic benefit, for the production and refinement of synthetic scaffolds, and from our mathematical modelling work which we anticipate would be readily adaptable for related applications.
The general public - In addition to the broad benefits that understanding fundamental bioscience brings in the longer term (32x gross value added per public spend), this work addresses directly key areas of health that have the potential to impact both on acute genetic diseases as well as long term health of the general population. The potential for our work in terms of tissue repair and regeneration presents one opportunity to engage through our fundamental discovery science. Our image and movie data are also extremely useful for high impact public engagement through displays and exhibitions.
Bioscience researchers - This project includes considerable opportunity to train the researchers involved in areas that go beyond the day-to-day research methodology. We have strong track records in facilitating the placement of staff in areas outside our core research activity including in intellectual property management, public engagement, clinical trials, and research policy and management. This demonstrates that the environment provided by our labs as well, as our two Universities more widely, is highly conducive to career development of our staff beyond academic, basic science research alone and thus contributes to the economic development of the nation. Our programme is very data intensive - notably from imaging, proteomics, and genomics work - and the management and analysis of such large (terabyte) datasets is applicable to many areas of professional life. Combined with mathematical modelling, our work provides a showcase opportunity for integration of multiple technologies and approaches to address a fundamental and highly significant problem in the biosciences. We hope this will be relevant and of great interest to many.
Who might benefit and how?
Clinicians - Dysregulation of collagen is the hallmark of some of the most debilitating features of normal ageing and life-threatening diseases; insufficient collagen can abrogate the mechanical properties of tissues and is associated with poor wound repair (which costs the NHS £2.5 billion p.a.), as well as osteoarthritis (8 million sufferers in the UK (Versus Arthritis UK website)) and tendinopathy (1-in-4 over 40 y.o.) for which there are no effective treatments. Conversely, fibrosis - the dysregulated accumulation of collagen in place of functional tissue - is associated with 45% of all deaths (including cardiovascular disease and cancer). Progress in treating these diseases has been hindered because of poor understanding of how cells synthesise, maintain, and repair collagen-rich tissues. A deep understanding of the fundamental basic science of collagen homeostasis is an elusive cornerstone of biology. Our work could identify new targets for clinical genetics, extending to analysis of patient cohorts (such as ALSPAC) to derive new insight into onset and progression of bone and joint degeneration during ageing. Our systems to perturb and model the systems, notably in wound situations have significant potential for those working in these areas, both for acute wound treatment and in relation to fibrosis.
Industry - There is great interest in the possibility to subvert existing cellular pathways for therapeutic benefit. We have clear plans in place for direct engagement, but many others will derive value from our work in relation to engineering of cells and tissues for therapeutic benefit, for the production and refinement of synthetic scaffolds, and from our mathematical modelling work which we anticipate would be readily adaptable for related applications.
The general public - In addition to the broad benefits that understanding fundamental bioscience brings in the longer term (32x gross value added per public spend), this work addresses directly key areas of health that have the potential to impact both on acute genetic diseases as well as long term health of the general population. The potential for our work in terms of tissue repair and regeneration presents one opportunity to engage through our fundamental discovery science. Our image and movie data are also extremely useful for high impact public engagement through displays and exhibitions.
Bioscience researchers - This project includes considerable opportunity to train the researchers involved in areas that go beyond the day-to-day research methodology. We have strong track records in facilitating the placement of staff in areas outside our core research activity including in intellectual property management, public engagement, clinical trials, and research policy and management. This demonstrates that the environment provided by our labs as well, as our two Universities more widely, is highly conducive to career development of our staff beyond academic, basic science research alone and thus contributes to the economic development of the nation. Our programme is very data intensive - notably from imaging, proteomics, and genomics work - and the management and analysis of such large (terabyte) datasets is applicable to many areas of professional life. Combined with mathematical modelling, our work provides a showcase opportunity for integration of multiple technologies and approaches to address a fundamental and highly significant problem in the biosciences. We hope this will be relevant and of great interest to many.
Organisations
- University of Manchester (Collaboration, Lead Research Organisation)
- University of Cologne (Collaboration)
- Chinese Academy of Sciences (Collaboration)
- University Hospital Cologne International (Collaboration)
- Goethe University Frankfurt (Collaboration)
- Case Western Reserve University (Collaboration)
- Australian Institute of Tropical Health and Medicine (Collaboration)
- University of Bristol (Collaboration)
Publications
Dudek M
(2023)
Mechanical loading and hyperosmolarity as a daily resetting cue for skeletal circadian clocks.
in Nature communications
Dudek M
(2021)
Circadian time series proteomics reveals daily dynamics in cartilage physiology
in Osteoarthritis and Cartilage
Dudek M
(2023)
The clock transcription factor BMAL1 is a key regulator of extracellular matrix homeostasis and cell fate in the intervertebral disc.
in Matrix biology : journal of the International Society for Matrix Biology
Dudek M
(2023)
The circadian clock and extracellular matrix homeostasis in aging and age-related diseases.
in American journal of physiology. Cell physiology
Etich J
(2023)
TAPT1-at the crossroads of extracellular matrix and signaling in Osteogenesis imperfecta.
in EMBO molecular medicine
Hellicar J
(2022)
Supply chain logistics - the role of the Golgi complex in extracellular matrix production and maintenance.
in Journal of cell science
Jensen OE
(2023)
Couple stresses and discrete potentials in the vertex model of cellular monolayers.
in Biomechanics and modeling in mechanobiology
McCaughey J
(2021)
A general role for TANGO1, encoded by MIA3, in secretory pathway organization and function.
in Journal of cell science
Musiime M
(2021)
Collagen Assembly at the Cell Surface: Dogmas Revisited.
in Cells
Revell C
(2023)
Modeling collagen fibril self-assembly from extracellular medium in embryonic tendon
in Biophysical Journal
Revell CK
(2021)
Collagen fibril assembly: New approaches to unanswered questions.
in Matrix biology plus
Rogers N
(2023)
Tick tock, the cartilage clock.
in Osteoarthritis and cartilage
Stevenson NL
(2021)
Giantin is required for intracellular N-terminal processing of type I procollagen.
in The Journal of cell biology
Vitali T
(2023)
Vimentin intermediate filaments provide structural stability to the mammalian Golgi complex.
in Journal of cell science
Yeung C
(2023)
Mmp14 is required for matrisome homeostasis and circadian rhythm in fibroblasts
in Matrix Biology
Description | Because of the COVID pandemic the start of experiments was significantly delayed, impacting the progress made under the award. However, since then, we have made significant progress and have generated several peer-reviewed research publications relating to different aspects of collagen synthesis, assembly and function, and also its control by the circadian clock. These are detailed in the publications section of Researchfish. In the past year these outputs have disseminated our discoveries on the reciprocal relationship and importance of extracellular matrix regulating the circadian clock and vice versa, the role of the cytoskeleton in controlling Golgi structure, and a paper on the modelling of collagen assembly, which was highlighted by the editors at Nature Cell Biology. We also have a number of studies submitted as preprints, which are currently undergoing review at scientific journals, describing non-canonical procollagen secretion and the role endosomal traffic in matrix homeostasis. Other findings made during the award are being prepared for publication currently, describing the role of golgins in matrix production, the role of the clock in mechanosensing pathways, and how the clock alters collagen deposition during wound healing the role of immune cells in controlling this process. The outputs generated so far on the award have addressed several of the initial objectives, and the studies in preparation also address objectives as initially outlined in the original award. We are continuing to work on the other objectives, with the aim of publishing these studies before the end of the grant at the end of 2025 (the grant was awarded a no-cost extension to run to the end of December 2025). |
Exploitation Route | We expect to find way of modulating matrix expression and synthesis to help in wound healing, in the treatment of fibrosis, and in tissue regeneration. |
Sectors | Healthcare Manufacturing including Industrial Biotechology Pharmaceuticals and Medical Biotechnology |
Description | Boots No.7/BBSRC CTP PhD studentship |
Amount | £130,000 (GBP) |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 08/2023 |
End | 09/2027 |
Description | Investigating circadian regulation of wound repair in vivo and in vitro |
Amount | £31,456 (GBP) |
Funding ID | BB/W018594/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 06/2022 |
End | 06/2025 |
Title | Conditional collagen-I knockout mouse |
Description | We crossed the Col1a1-F/F mouse with the Col1a2-CreERT2 mouse to generate a tamoxifen inducible collagen-I knockout mouse. We have not published this yet but will do so late 2022 when the mouse will be available to collaborators under agreement. |
Type Of Material | Biological samples |
Year Produced | 2022 |
Provided To Others? | No |
Impact | To identify the impact of collagen KO in disease symptom modification. |
Title | Delta19 dom neg clock zebrafish model |
Description | Transgenic zebrafish model (Delta19 dom neg clock) where the clock is disrupted specifically in either macrophages or neutrophils to investigate clock function in inflammatory cells during wound repair. |
Type Of Material | Biological samples |
Year Produced | 2022 |
Provided To Others? | No |
Impact | None yet |
Title | Golgin KO RPE1 cell lines expressing a RUSHable BGNmCh to study secretory traffic |
Description | The RPE1 cell lines are either wild-type or CRISPR knock-out for the golgins GMAP-210 or GOLGA3. They stably express the extracellular matrix protein Biglycan contains tags for visualisation (mCherry) and for synchronised export from the ER (using the RUSH method). |
Type Of Material | Cell line |
Year Produced | 2022 |
Provided To Others? | No |
Impact | None yet. |
Title | MC3T3 cells with COL1A2 KI's |
Description | Mouse osteoblast MC3T3 cells in which the COL1A2 locus has been engineered by CRISPR to knock-in either the HiBit tag, GFP or a dual HiBit/GFP. These cells can be used to study secretory traffic of collagen type I. |
Type Of Material | Cell line |
Year Produced | 2023 |
Provided To Others? | No |
Impact | None yet |
Title | NIH3T3 Dendra2-procollagen |
Description | We have generated a cell line based on NIH3T3 cells in which we used CRISPR-Cas9 to introduce Dendra2 into the endogenous Col1a2 locus. The insertion places Dendra2 (a photoswithable protein) between the signal peptide and the N-propeptide of proa2(I). This cell line enables us to observe the assembly of collagen fibrils in culture. We have a paper under review at the moment describing the use of this cell line to study collagen fibril assembly at the plasma membrane of the cells. The major discovery in this paper is that there are two routes for secretion of collagen: one is for the secretion of soluble procollagen to the ECM and the other directs procollagen and collagen to sites of fibril formation. The identification of two secretion routes is a major step forward in understanding collagen homeostasis in health and disease. |
Type Of Material | Cell line |
Year Produced | 2022 |
Provided To Others? | No |
Impact | We will be able to study the consequences of mutations in collagen genes, mutations in all other matrix genes, the importance of Golgi proteins, and the importance of other secretory pathway proteins on collagen homeostasis. |
Title | NLuc-collagen-I mouse |
Description | We have previously shown that we can introduce nanoluciferase (NLuc) into the Col1a2 locus between the signal peptide and the N-propeptide to produce a fully quantifiable collagen secretion system in cell culture (https://www.mdpi.com/2073-4409/9/9/2070 PMID 32927811). With this system we showed that cells secrete 100,000 procollagen molecules per hour and in a circadian clock-regulated manner. We have now taken this system further and generated the NLuc mouse. The homozygous mouse dies before birth. However, the heterozygous mouse survives with a moderate phenotype (dwarfism). We are preparing a manuscript describing this mouse. This mouse will be made available to collaborators under agreement. |
Type Of Material | Biological samples |
Year Produced | 2022 |
Provided To Others? | No |
Impact | Use this mouse for in vivo testing of small compounds to regulate collagen synthesis e.g. in the treatment of fibrosis. |
Title | SILAC mouse and tissue samples |
Description | Mice were labelled with stable isotopes to allow for quantitative proteomics to assess protein turnover in various tissues. This includes matrix-rich tissues such as tendon, but others will also be analysed. Tissues have been prepared and are undergoing analysis. |
Type Of Material | Biological samples |
Year Produced | 2023 |
Provided To Others? | No |
Impact | None yet |
Title | Vimentin and GORAB KO mouse fibroblasts |
Description | Mouse embryo fibroblasts in which vimentin, GORAB or both proteins were knocked-out using CRISPR-Cas9. |
Type Of Material | Cell line |
Year Produced | 2022 |
Provided To Others? | No |
Impact | A paper that is currently in preparation |
Title | Zebrafish KO lines for Golgi proteins GORAB and GOLGA3 |
Description | Stable knock-out zebrafish lines in which mutations in the GORAB or GOLGA3 locus were generated to abolish protein expression. |
Type Of Material | Biological samples |
Year Produced | 2023 |
Provided To Others? | No |
Impact | None yet |
Title | A general role for MIA3/TANGO1 in secretory pathway organization and function |
Description | Raw data associated with a manuscript describing engineered knockout of Mia3/TANGO1 in human cells. |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | Data used to underpin publication |
URL | https://data.bris.ac.uk/data/dataset/xbao2ekjv5c124o2k0frhq7v6/ |
Title | Mia3 enables efficient secretion by constraining COPII vesicle budding - cell derived matrix |
Description | Proteomics data of cell-derived extracellular matrix Following knockout of Mia3 encoding both TANGO1S and TANGO1L we have analysed the extracellular matrix deposited by these cells using TMT mass spectrometry. |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | Publication and further funding |
URL | https://www.ebi.ac.uk/pride/archive/projects/PXD024214 |
Title | Mia3 enables efficient secretion by constraining COPII vesicle budding - secreted proteome |
Description | Analysis of secreted proteome from cells engineered with knockout of Mia3 gene isoforms encoding TANGO1L and TANGO1S |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | Publication and further funding |
URL | https://www.ebi.ac.uk/pride/archive/projects/PXD024221 |
Title | RNAseq of 6 genome edited human RPE1 cell lines (compared to the parental control) disrupting the MIA3 gene. |
Description | Accession E-MTAB-10503 Study type RNA-seq of total RNA EFO, Cell line - High-throughput sequencing Organism Homo sapiens Description We generated 6 cell lines disrupting the MIA3 gene using CRISPR/Cas9. We have then run RNAseq to compare these 6 lines to the control (Wild-type (WT) parental cell line). The aim of the study was to define changes in the transcriptome following loss of different isoforms of the TANGO1 protein encoded by the Mia3 gene. These data are linked to proteomic data submitted to PRIDE with accession numbers PXD024214 and PXD024221. |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | Yes |
Impact | Publication of the work, future funding. |
URL | https://www.ebi.ac.uk/biostudies/arrayexpress/studies/E-MTAB-10503 |
Description | Collaboration with Ben Faber |
Organisation | University of Bristol |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Information on circadian regulation of matrix-rich tissues |
Collaborator Contribution | BioBank analysis of osteoarthritis |
Impact | None yet |
Start Year | 2023 |
Description | Collaboration with Lei Wang |
Organisation | Chinese Academy of Sciences |
Country | China |
Sector | Public |
PI Contribution | Proteomics data |
Collaborator Contribution | Reagents to study the Golgi protein FAM20C |
Impact | None yet |
Start Year | 2022 |
Description | Collaboration with Plastic Surgery and Skin BioBank |
Organisation | University of Manchester |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Access to patient samples |
Collaborator Contribution | The clinicians are Adam Reid and Jason Wong. It is for provision of patient samples |
Impact | None yet |
Start Year | 2021 |
Description | Collaboration with consultant orthopaedic surgeon (Leela Biant) in Manchester |
Organisation | University of Manchester |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Analysis of cell matrix and circadian clock in patient samples. |
Collaborator Contribution | Provision of patient materials |
Impact | None yet |
Start Year | 2021 |
Description | David Whitmore |
Organisation | Australian Institute of Tropical Health and Medicine |
Country | Australia |
Sector | Public |
PI Contribution | The sLoLa team reached out to Prof Whitmore for advice on circadian biology in zebrafish |
Collaborator Contribution | Prof Whitmore is helping with advice and by providing tools to study the circadian clock in zebrafish |
Impact | None yet |
Start Year | 2021 |
Description | Frankfurt/Cologne clinical genetics |
Organisation | Goethe University Frankfurt |
Country | Germany |
Sector | Academic/University |
PI Contribution | Collaboration with clinical genetics colleagues where we examined the formation and function of primary cilia and he deposition of extracellular matrix in patient cells from a newly identified case. |
Collaborator Contribution | The partners identified this patient and characterized the clinical changes as well as working with us on phenotyping cells from the individual. |
Impact | Manuscript submitted |
Start Year | 2021 |
Description | Frankfurt/Cologne clinical genetics |
Organisation | University Hospital Cologne International |
Country | Germany |
Sector | Hospitals |
PI Contribution | Collaboration with clinical genetics colleagues where we examined the formation and function of primary cilia and he deposition of extracellular matrix in patient cells from a newly identified case. |
Collaborator Contribution | The partners identified this patient and characterized the clinical changes as well as working with us on phenotyping cells from the individual. |
Impact | Manuscript submitted |
Start Year | 2021 |
Description | Frankfurt/Cologne clinical genetics |
Organisation | University of Cologne |
Department | Center for Biochemistry |
Country | Germany |
Sector | Academic/University |
PI Contribution | Collaboration with clinical genetics colleagues where we examined the formation and function of primary cilia and he deposition of extracellular matrix in patient cells from a newly identified case. |
Collaborator Contribution | The partners identified this patient and characterized the clinical changes as well as working with us on phenotyping cells from the individual. |
Impact | Manuscript submitted |
Start Year | 2021 |
Description | Frankfurt/Cologne clinical genetics |
Organisation | University of Cologne |
Country | Germany |
Sector | Academic/University |
PI Contribution | Collaboration with clinical genetics colleagues where we examined the formation and function of primary cilia and he deposition of extracellular matrix in patient cells from a newly identified case. |
Collaborator Contribution | The partners identified this patient and characterized the clinical changes as well as working with us on phenotyping cells from the individual. |
Impact | Manuscript submitted |
Start Year | 2021 |
Description | Joan Chang |
Organisation | University of Manchester |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | The sLoLa team liaises closely with Joan, who is an active member of the group, although not funded directly by the award. |
Collaborator Contribution | Joan contributes extensive knowledge of matrix cell biology and is working on similar topic to the sLoLa. |
Impact | None yet |
Start Year | 2021 |
Description | Rachel Lennon |
Organisation | University of Manchester |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Sharing tissues from the SILAC mouse to study kidney extracellular matrix |
Collaborator Contribution | Contribution of mouse tissues and proteomics expertise |
Impact | None yet |
Start Year | 2022 |
Description | Ruth Mitchell |
Organisation | University of Bristol |
Department | Medical School |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We are working with Dr Mitchell to study population genetics in the context of protein trafficking in the secretory pathway |
Collaborator Contribution | Dr Mitchell is analysing population genetics to look for associations between physical traits and defects in the secretory pathway. |
Impact | None yet |
Start Year | 2021 |
Description | Suneel Apte |
Organisation | Case Western Reserve University |
Country | United States |
Sector | Academic/University |
PI Contribution | Mass spec analysis of connective tissue |
Collaborator Contribution | ECM degradomics expertise |
Impact | None so far |
Start Year | 2023 |
Description | Article published in the Mirror newspaper |
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 | Article published in the Mirror newspaper on benefits of exercising at different times. Based upon recent publication in Nature Comms. https://www.mirror.co.uk/lifestyle/health/exercising-right-time-each-day-31879016 |
Year(s) Of Engagement Activity | 2023 |
Description | Exhibit at University of Manchester 2022 Community Festival |
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 | Joe Swift developed and presented an exhibit (posters and hands-on activities), 'Why are bones strong and brains squishy?', at the University of Manchester 2022 Community Festival. The exhibition has been attended by hundreds of children (typically aged 4-11) and their parents. The exhibit explained the central role of biophysics in understanding how our bodies work. |
Year(s) Of Engagement Activity | 2022 |
Description | ISAB meeting |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | There was an in-person/hybrid meeting between sLoLa team and ISAB, held in Bristol in January 2023. There were presentations, discussions, and feedback was provided by the ISAB. Elly Tyacke from the BBSRC also attended the first day of the meeting. |
Year(s) Of Engagement Activity | 2023 |
Description | On-line public engagement video- cell factory |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Schools |
Results and Impact | This was an on-line video for the Biodiscovery 2021 even during British Science Week, entitled 'From Proteins to People: the Factory of the Cell'. It was targeted at secondary school pupils. I was hard to gauge the impact of the exercise. |
Year(s) Of Engagement Activity | 2021 |
Description | Press release on clock regulation, matrix and beauty sleep |
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 | Press release from the UoM on a study where it was shown that the circadian clock regulates collagen production, which is important for skin and bone health. This suggests that sleep could improve skin (and possibly bone), hence the beauty sleep connotation. |
Year(s) Of Engagement Activity | 2021 |
URL | https://www.manchester.ac.uk/discover/news/beauty-sleep-could-be-real-say-body-clock-biologists/ |
Description | Qing-Jun Meng provided expert comments on news article in Nature |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Expert comments that were included in a magazine news article |
Year(s) Of Engagement Activity | 2022 |
Description | Qing-Jun Meng talked about his research into body clocks and breast cancer drugs on BBC Radio Scotland on 6 October 2022. |
Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Radio interview discussing science done in the Meng lab |
Year(s) Of Engagement Activity | 2022 |
Description | Qing-Jun Meng was featured on BBC Radio Manchester and UK Health Radio talking about chronotherapy and cancer. |
Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Radio broadcasts discussing work in the Meng lab |
Year(s) Of Engagement Activity | 2022 |
Description | Talk at New Scientist conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Invited speaker at the New Scientist's Instant Expert: The Genetics Revolution, Recent Advances in Genetic Manipulation - from the bench to bedside. Held on Saturday 9 March, 10am - 5pm at Conway Hall, 25 Red Lion Square, London, WC1R 4RL |
Year(s) Of Engagement Activity | 2023 |
Description | University 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 | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | Press release on benefits of exercise at different times. Based upon output published in Nature Comms. https://www.manchester.ac.uk/discover/news/exercise-at-consistent-times-could-help-re-align-your-body-clocks-for-better-skeletal-health-and-performance-scientists-suggest/ |
Year(s) Of Engagement Activity | 2023 |
Description | We the Curious 2022 public engagement event |
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 | Public engagement event held at Open City Lab. Title - Circadian rhythms and matrix secretion. Aimed at schools and kids with their carers. |
Year(s) Of Engagement Activity | 2022 |
Description | We the curious YouTube videos on sleep |
Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | YouTube videos on research into sleep performed by the research team. Aimed at the general public. It is associated with a pending exhibition at We The Curious science centre. Video 1 is entitled 'How is Your Sleep?' and the 2nd video is on 'What part of sleep is the research exploring?' https://www.youtube.com/watch?v=-kAiX6r5lWQ https://www.youtube.com/watch?v=0jq2EHUvzbg |
Year(s) Of Engagement Activity | 2023 |
Description | sLoLa ISAB |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | The sLoLa award started in January 2021 immediately before the first lockdown at the start of the COVID-19 pandemic. Therefore we have had very little opportunity for outreach or to meet other scientists. We did, however, organise a meeting with our scientific advisory board via zoom.us in June 2020, we had a virtual away day with our groups from Bristol and Manchester in September 2020, a virtual retreat in September 2021, and a 'get-together' in December 2021. |
Year(s) Of Engagement Activity | 2020,2021 |
Description | sLoLa ISAB meeting |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | There was an in-person/hybrid meeting between sLoLa team and ISAB, held in Manchester in January 2024. There were presentations, discussions, and feedback was provided by the ISAB. |
Year(s) Of Engagement Activity | 2024 |