Molecular mechanisms of the targeting of tail-anchored membrane proteins to peroxisomes and mitochondria in mammalian cells
Lead Research Organisation:
University of Exeter
Department Name: Biosciences
Abstract
Eukaryotic cells contain distinct membrane-bound organelles, which compartmentalize specific cellular proteins to fulfil a variety of essential cellular functions. Proper sorting and delivery of organelle-specific proteins is of fundamental importance to maintain organelle functionality and viability of the cell and the organism. Trans-membrane proteins are usually sorted to and inserted into their target membrane during their synthesis. Tail-anchored (TA) proteins represent an interesting exception, as due to their short membrane tail, they must be sorted and inserted after (and not during) their synthesis in the cytoplasm. Unexpectedly, we discovered that a growing number of TA proteins are shared by peroxisomes (PO) and mitochondria (MITO) (e.g. Fis1, Mff or GDAP1, which contribute to organelle division) suggesting a closer functional interrelationship between both organelles. However, other TA proteins are exclusively on PO (e.g. ACBD5, ALDH3A2V), on MITO or on the endoplasmic reticulum (ER). Thus, organelle-specific targeting processes must exist to ensure that the proteins reach the correct cellular compartment to fulfil their proper functions. How this important targeting decision is regulated, what machinery is involved, and if part of the machinery is shared by PO and MITO is largely unknown. At present, only proteins contributing to the ER sorting machinery have been characterized in more detail, whereas knowledge on MITO and PO TA protein targeting remains scarce. TA proteins fulfil a variety of essential organelle and cellular functions requiring membrane anchorage (e.g. organelle division, vesicle fusion, apoptosis, viral defence). PO and MITO are essential for human health and development. They have important metabolic functions in lipid and ROS metabolism, thus influencing neuronal development, lipid homeostasis and ageing.
In this project we will address the molecular mechanism by which TA proteins are sorted and delivered to PO and MITO in mammalian cells. Our preliminary screening experiments, which led to the identification of previously unknown TA proteins on PO, and on both PO and MITO, have generated tools which now enable for the first time to study the organelle-specific targeting. We will assess if Pex19, a PO import receptor, is essential for TA protein targeting to PO. By protein-protein interaction studies and mutational analyses of TA proteins we will determine Pex19 binding to selected TA proteins, thereby defining the Pex19 binding motif. To identify new cytosolic interaction partners of Pex19 involved in TA protein sorting, we will apply a pull-down strategy combined with quantitative mass spectrometry. To assess if proteins of the ER targeting machinery for TA proteins (e.g. Sg2A, Get and heat shock proteins) contribute to PO and MITO targeting we will perform "knock down" studies in cell culture to silence their function and monitor sorting of fluorescent TA proteins. We will reveal if Sg2A functions as a general sorting station for TA proteins. Finally, we aim at identifying novel components of the TA protein import machinery for PO and MITO by applying pull down strategies, a combination of in vitro translation, mass spectrometry, and expression studies in mammalian cell culture.
In summary, we will combine molecular cell biology, biochemical approaches and imaging to elucidate the sorting mechanism and to identify novel factors that support TA protein targeting to PO and MITO. Understanding how the organelle-specific targeting of TA proteins is controlled will be of fundamental biological and medical importance. It has high potential to contribute to the discovery of novel disorders based on mistargeting of TA proteins and new targets to e.g. inhibit virus replication.
In this project we will address the molecular mechanism by which TA proteins are sorted and delivered to PO and MITO in mammalian cells. Our preliminary screening experiments, which led to the identification of previously unknown TA proteins on PO, and on both PO and MITO, have generated tools which now enable for the first time to study the organelle-specific targeting. We will assess if Pex19, a PO import receptor, is essential for TA protein targeting to PO. By protein-protein interaction studies and mutational analyses of TA proteins we will determine Pex19 binding to selected TA proteins, thereby defining the Pex19 binding motif. To identify new cytosolic interaction partners of Pex19 involved in TA protein sorting, we will apply a pull-down strategy combined with quantitative mass spectrometry. To assess if proteins of the ER targeting machinery for TA proteins (e.g. Sg2A, Get and heat shock proteins) contribute to PO and MITO targeting we will perform "knock down" studies in cell culture to silence their function and monitor sorting of fluorescent TA proteins. We will reveal if Sg2A functions as a general sorting station for TA proteins. Finally, we aim at identifying novel components of the TA protein import machinery for PO and MITO by applying pull down strategies, a combination of in vitro translation, mass spectrometry, and expression studies in mammalian cell culture.
In summary, we will combine molecular cell biology, biochemical approaches and imaging to elucidate the sorting mechanism and to identify novel factors that support TA protein targeting to PO and MITO. Understanding how the organelle-specific targeting of TA proteins is controlled will be of fundamental biological and medical importance. It has high potential to contribute to the discovery of novel disorders based on mistargeting of TA proteins and new targets to e.g. inhibit virus replication.
Technical Summary
In this project we will elucidate the molecular mechanism by which tail-anchored (TA) membrane proteins are sorted and delivered to peroxisomes (PO) and mitochondria (MITO) in mammalian cells. We recently showed that PO and MITO share several TA proteins, and have now identified TA proteins which are exclusively targeted to PO. How organelle-specific sorting is mediated, what machinery is involved, and if part of the sorting machinery is shared by PO and MITO is largely unknown. The molecular tools we generated now allow for the first time to address these fundamental questions in detail.
In a first part of the project, the role of Pex19, a shuttle receptor for PO trans-membrane proteins, as an essential factor in PO TA protein targeting will be analyzed. Pex19 binding to selected TA proteins will be monitored in an in vitro translation assay and by immunoprecipitation. We will use mutated versions of TA proteins and bioinformatics to define the Pex19 binding motif. Furthermore, we will use Pex19 as bait to search for additional cytosolic interaction partners in in vitro and in vivo pull down approaches. In a second part, RNAi-mediated silencing is planned to examine if Sg2A and other proteins of the ER targeting machinery (e.g. mammalian homologues of get4/5, hsp104/70/40) contribute to TA protein targeting to PO and MITO. Novel components of a potential Sg2A containing central docking complex will be identified by a combined in vitro translation/pull down approach and mass spectrometry. In a third part, we will make use of fatty aldehyde dehydrogenase ALDH3A2 (targeted to the ER) and its PO splice variant ALDH3A2V to search for common and unique binding partners involved in the targeting to PO. Furthermore, we will exploit the observation that ACBD5, an exclusively PO TA protein, is relocated to MITO in Pex19-deficient cells to identify the receptor for TA protein targeting to MITO.
In a first part of the project, the role of Pex19, a shuttle receptor for PO trans-membrane proteins, as an essential factor in PO TA protein targeting will be analyzed. Pex19 binding to selected TA proteins will be monitored in an in vitro translation assay and by immunoprecipitation. We will use mutated versions of TA proteins and bioinformatics to define the Pex19 binding motif. Furthermore, we will use Pex19 as bait to search for additional cytosolic interaction partners in in vitro and in vivo pull down approaches. In a second part, RNAi-mediated silencing is planned to examine if Sg2A and other proteins of the ER targeting machinery (e.g. mammalian homologues of get4/5, hsp104/70/40) contribute to TA protein targeting to PO and MITO. Novel components of a potential Sg2A containing central docking complex will be identified by a combined in vitro translation/pull down approach and mass spectrometry. In a third part, we will make use of fatty aldehyde dehydrogenase ALDH3A2 (targeted to the ER) and its PO splice variant ALDH3A2V to search for common and unique binding partners involved in the targeting to PO. Furthermore, we will exploit the observation that ACBD5, an exclusively PO TA protein, is relocated to MITO in Pex19-deficient cells to identify the receptor for TA protein targeting to MITO.
Planned Impact
This work is curiosity-driven and discovery-based, and aims to understand fundamental processes in mammalian cell biology which have great potential to be exploited in the pharmacological and public health sectors. Moreover, this work can contribute to the generation of novel tools, e.g. in the prediction of receptor binding to candidate proteins. The reason for this potential is that the mechanisms of organelle-specific targeting of proteins or organelle interplay and cross-talk are poorly understood, but are essential for cellular viability and development of the organism. In particular, mechanistic insights into the targeting of tail-anchored (TA) proteins to peroxisomes (PO) and mitochondria (MITO) have high potential to create a new field of research and are essential to understand the PO-MITO interrelationship and membrane protein import into PO but also to identify new biological functions of PO in animals and humans. Hence, novel insights generated from this work will be of interest to many aspects of cell biological research, and of particular importance for understanding protein targeting and missorting in cellular physiology and pathophysiology. TA proteins fulfil many key functions at their specific membranes, and loss of function leads to pathophysiological conditions and disease. Moreover, viruses are known to exploit TA proteins and their targeting mechanisms to ensure proper replication of their RNAs or to disturb the cellular defence. Therefore, a thorough dissection of the individual sorting steps required to target TA proteins to their correct destinations has the potential to lead to the detection of new genetic disorders caused by the mistargeting of individual TA protein families and of possible new targets e.g. to inhibit virus replication in infected individuals.
Knowledge gained from this study promises to help the identification of novel targets for drug development (of benefit to the UK and European pharmaceutical and health sectors) as well as in the diagnosis of pathophysiological conditions and disorders (public health sector). Hence, we expect opportunities for commercial exploitation. The University of Exeter has excellent links with the wider public with regular events with contributions from research staff. Researchers make regular school visits to explain their research and run events as part of National Science week. Programmes such as this and other outreach activities are critical for the long-term maintenance of the UK science base. This is also aided by the transfer of knowledge and skills between academia and industry. The PDRA and Technician will both receive full and relevant training. Several of my former PhD students are now working within the biotechnology or biomedical sector.
Knowledge gained from this study promises to help the identification of novel targets for drug development (of benefit to the UK and European pharmaceutical and health sectors) as well as in the diagnosis of pathophysiological conditions and disorders (public health sector). Hence, we expect opportunities for commercial exploitation. The University of Exeter has excellent links with the wider public with regular events with contributions from research staff. Researchers make regular school visits to explain their research and run events as part of National Science week. Programmes such as this and other outreach activities are critical for the long-term maintenance of the UK science base. This is also aided by the transfer of knowledge and skills between academia and industry. The PDRA and Technician will both receive full and relevant training. Several of my former PhD students are now working within the biotechnology or biomedical sector.
Publications
Barel O
(2017)
Deleterious variants in TRAK1 disrupt mitochondrial movement and cause fatal encephalopathy.
in Brain : a journal of neurology
Bonekamp NA
(2013)
Cytochemical detection of peroxisomes and mitochondria.
in Methods in molecular biology (Clifton, N.J.)
Camões F
(2015)
New insights into the peroxisomal protein inventory: Acyl-CoA oxidases and -dehydrogenases are an ancient feature of peroxisomes.
in Biochimica et biophysica acta
Castro IG
(2018)
A role for Mitochondrial Rho GTPase 1 (MIRO1) in motility and membrane dynamics of peroxisomes.
in Traffic (Copenhagen, Denmark)
Castro IG
(2018)
Miro1 - the missing link to peroxisome motility.
in Communicative & integrative biology
Costello J
(2017)
Cloudy with a chance of biology...
in Laboratory News
Costello JL
(2017)
Predicting the targeting of tail-anchored proteins to subcellular compartments in mammalian cells.
in Journal of cell science
Costello JL
(2017)
Peroxisomal ACBD4 interacts with VAPB and promotes ER-peroxisome associations.
in Cell cycle (Georgetown, Tex.)
Costello JL
(2017)
ACBD5 and VAPB mediate membrane associations between peroxisomes and the ER.
in The Journal of cell biology
Costello JL
(2018)
Unloosing the Gordian knot of peroxisome formation.
in Current opinion in cell biology
Description | Tail-anchored (TA) membrane proteins are critical for a variety of cellular processes and mutations in individual TA proteins cause a number of severe inherited disorders. In order to function correctly the targeting of TA proteins to the appropriate organelle membrane is essential. The mechanisms of organelle-specific targeting are poorly understood, but are essential for cellular viability and development of the organism. The overall goal of this project is to elucidate the molecular mechanism by which tail-anchored (TA) membrane proteins are targeted to peroxisomes and mitochondria in mammalian cells. TA proteins play key roles in important cellular processes requiring membrane anchorage such as protein translocation, organelle division, apoptosis, and viral defense, whereas peroxisomes and mitochondria are crucial for energy and lipid metabolism and influence neuronal development and ageing processes. We discovered that a growing number of TA proteins are shared by peroxisomes and mitochondria. These findings suggest a closer functional interrelationship between both organelles and support our medically relevant concept of the "peroxisome-mitochondria connection". We identified novel TA proteins on peroxisomes or shared by multiple organelles. Their function and importance for human health is currently investigated. We provided first evidence that the TA protein GDAP1 (ganglioside-induced differentiation associated protein 1), involved in Charcot-Marie-Tooth disease, is functionally linked to peroxisomal division and dynamics in neurons. Combining our findings with published data on TA protein localization enabled us to allocate characteristic physicochemical parameters to different organelle groups. We discovered that a combination of transmembrane domain (TMD) hydrophobicity and tail charge determines organelle-specific targeting. We revealed that subtle alterations in those physicochemical parameters can shift TA protein targeting between organelles, explaining why peroxisomes and mitochondria share many TA proteins. We demonstrated that targeting of TA proteins to peroxisomes depends on the peroxisomal import receptor/chaperone PEX19. High affinity for PEX19 leads to peroxisomal targeting whilst a stepwise reduction in affinity results in mitochondrial and finally ER targeting. In cells lacking PEX19, peroxisomal TA proteins are targeted to mitochondria suggesting a potentially overlapping binding site which is competed for by different shuttling receptors or chaperones. Our classification of TA protein targeting allows for the first time successful prediction of the location of uncharacterized TA proteins. We identified new TA proteins at peroxisomes. One of them, MIRO1, was first localised at mitochondria, but we revealed that it also targets peroxisomes. We demonstrated that MIRO1 links peroxisomes to microtubule-dependent motor proteins and is involved in peroxisome motility and membrane dynamics in mammalian cells. It thus represents the missing adaptor for microtubule-dependent peroxisome motility. Two other TA proteins, ACBD4/5 localise to peroxisomes. We demonstrated that they mediate the formation of membrane contacts with the endoplasmic reticulum (ER). These contacts have important physiological functions. Our findings led to the diagnosis and characterisation of first patients with a deficiency in ACBD5. |
Exploitation Route | Our findings have increased our fundamental mechanistic understanding of the targeting of tail-anchored membrane proteins to different subcellular organelles. They allow to predict the targeting of uncharacterised human TA proteins and to study their organelle-specific and disease-related functions. TA proteins fulfil many key functions at their specific membranes, and loss of function leads to pathophysiological conditions and disease. Our findings (e.g. on ACBD4/5) will lead to a better understanding of the physiological role of peroxisome-ER membrane contacts and their metabolic cooperation. These findings will be beneficial for the diagnosis and treatment of patients suffering from a defect in ACBD5/organelle cooperation. Moreover, viruses are known to exploit TA proteins and their targeting mechanisms to ensure proper replication of their RNAs or to disturb the cellular defence. Our findings have the potential to contribute to the discovery of novel disorders e.g. based on mistargeting of TA proteins and new targets e.g. to inhibit virus replication in infected individuals. |
Sectors | Education,Healthcare,Pharmaceuticals and Medical Biotechnology |
Description | Our findings have so far contributed to a better understanding of peroxisome-mitochondria interplay and dual protein targeting which is medically relevant. Our findings have been used by other scientists to identify new membrane proteins which are targeted to both organelles. This resulted in the association of new functions with peroxisomes and greatly supported our concept of the peroxisome-mitochondria connection which is of biological and medical importance. Our findings allow the prediction of membrane protein targeting to specific organelle membranes. Our findings have led to the development of tools to target proteins to specific organelle membranes. Our findings have supported diagnostics of peroxisome-organelle based disorders (e.g. peroxisome-ER, peroxisome-mitochondria). |
First Year Of Impact | 2012 |
Sector | Education,Healthcare |
Impact Types | Cultural,Societal |
Description | Identification and characterization of the molecular defects underlying a novel disorder affecting peroxisomes and mitochondria |
Amount | ÂŁ30,000 (GBP) |
Funding ID | WT097835MF |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 01/2013 |
End | 11/2014 |
Description | Super-resolution imaging of peroxisomes |
Amount | ÂŁ9,000 (GBP) |
Organisation | University of Exeter |
Sector | Academic/University |
Country | United Kingdom |
Start | 08/2013 |
End | 12/2014 |
Title | Mathematical model of organelle/peroxisome dynamics and proliferation |
Description | The mathematical model developed helps to understand and to predict changes in organelle membrane dynamics and proliferation. This is helpful for the understanding of the mechanisms and parameters mediating organelle dynamics and the prediction of organelle dynamics in health and disease conditions, e.g. in patient cells with abnormal organelle phenotypes and numbers. |
Type Of Material | Model of mechanisms or symptoms - human |
Year Produced | 2018 |
Provided To Others? | Yes |
Impact | The mathematical model supports the understanding of the mechanisms and parameters mediating organelle dynamics and the prediction of organelle dynamics in health and disease conditions, e.g. in patient cells with abnormal organelle phenotypes and numbers. This has an impact on knowledge/understanding of these fundamental and medically relevant processes as well as on diagnostics/treatment options to overcome problems with organelle dynamics/morphology/proliferation |
URL | http://onlinelibrary.wiley.com/doi/10.1111/tra.12549/abstract |
Title | TA protein predictor |
Description | Based on our analyses, we were able to generate a predictor tool which enables to predict the localisation of tail-anchored membrane proteins in human cells (and mammals). |
Type Of Material | Model of mechanisms or symptoms - human |
Year Produced | 2015 |
Provided To Others? | Yes |
Impact | The tool allows to predict the targeting and localisation of tail-anchored (TA) membrane proteins in human (mammalian) cells. TA proteins are very important membrane adaptors involved in a variety of crucial cellular processes. Many TA proteins are involved in human disorders. However, the targeting and localisation of many TA proteins is unknown. Our predictor helps to associate uncharacterised TA proteins to subcellular compartments. Using this tool, we have associated novel functions with organelles and supported the diagnosis of uncharacterised disorders. |
Title | Mathematical model of peroxisome/organelle dynamics |
Description | The mathematical model helps to understand and predict organelle (peroxisome) dynamics in healthy and diseased cells |
Type Of Material | Computer model/algorithm |
Year Produced | 2018 |
Provided To Others? | Yes |
Impact | The mathematical model provided has increased understanding of organelle/peroxisome membrane dynamics in health and disease and can be exploited to further understand and predict alterations in peroxisome dynamics; it increased interest in the prediction and modulation of organelle morphology/numbers in order to protect/improve cellular functions. |
URL | http://onlinelibrary.wiley.com/doi/10.1111/tra.12549/abstract |
Title | Protein prediction datasets |
Description | Our datasets provide specific physicochemical properties of organelle membrane proteins encoded in the human genome which can be used to predict their targeting to specific subcellular compartments and to improve targeting of model proteins to specific organelles. |
Type Of Material | Database/Collection of data |
Year Produced | 2017 |
Provided To Others? | Yes |
Impact | The datasets provided have increased knowledge and awareness of targeting mechanisms/signals and increased interest in the prediction and modification of targeting signals for analysis of localisation. |
URL | http://doi.org/10.6084/m9.figshare.4758532 |
Title | TA protein datasets |
Description | We have generated a dataset of potential tail-anchored (TA) membrane proteins encoded in the human genome including physicochemical properties of the C-terminal domains. |
Type Of Material | Database/Collection of data |
Year Produced | 2015 |
Provided To Others? | Yes |
Impact | Our analyses enabled us to allocate specific physicochemical properties to each TA candidate protein and to classify subcellular localisation. This resulted in the identification of targeting signals for each group and in the development of a predictor tool for analysis of localisation. |
Description | GDAP1 cooperation |
Organisation | ETH Zurich |
Country | Switzerland |
Sector | Academic/University |
PI Contribution | Contributed intellectual input, experimental data and reagents to study the localisation and function of GDAP1, a protein involved in Charcot Marie Tooth disease. |
Collaborator Contribution | Contributed intellectual input, experimental data and neuronal model system to study the localisation and function of GDAP1, a protein involved in Charcot Marie Tooth disease. |
Impact | Joint Publication: Huber, N., S. Guimaraes, M. Schrader, U. Suter, A. Niemann. Charcot-Marie-Tooth disease-associated mutants of GDAP1 dissociate its roles in peroxisomal and mitochondrial fission. EMBO Rep. 14(6):545-52, 2013. DOI: 10.1038/embor.2013.56. This cooperation is multi-disciplinary and combines molecular cell biology and neurobiology. |
Start Year | 2012 |
Description | TA protein collaboration |
Organisation | Academic Medical Center |
Country | Netherlands |
Sector | Academic/University |
PI Contribution | Identification, analysis and diagnostics of novel tail-anchored membrane proteins in health and disease. We are covering all aspects of molecular cell biology. |
Collaborator Contribution | Our partner is covering all diagnostic aspects including patient data and provides us with patient cells. |
Impact | Discovery of new TA protein-related disorders. Improved diagnostics. Manuscripts are currently in preparation. This collaboration is multidisciplinary and combines molecular cell biology and biomedicine. |
Start Year | 2015 |
Description | TRAK1 cooperation |
Organisation | Sheba Medical Centre |
Country | Israel |
Sector | Academic/University |
PI Contribution | Cooperative research to characterise a new organelle-based defect; molecular cell biology and microscopy to characterize the role of peroxisomes |
Collaborator Contribution | contribution of unpublished data, reagents, cells; experimental characterisation of mitochondria |
Impact | co-authored publication; visit at partner institution; planning of further cooperations/grant proposals; multi-disciplinary cooperation involving molecular cell biology and biomedicine/medical genetics/diagnostics |
Start Year | 2014 |
Description | ACAD11 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 | Public/other audiences |
Results and Impact | Press Release "New model gives scientists insight into cells' fat-metabolisers" featuring our publication in BBA- Molecular Cell Research The press release promoted our recognition in the field and sparked discussions with experts and the public. |
Year(s) Of Engagement Activity | 2014 |
URL | http://biosciences.exeter.ac.uk/news/research/title_419085_en.html |
Description | Biosciences Away Day |
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 | Approx. 50 scientists attended a presentation, which sparked questions and discussions and supported ideas for further fund-raising and collaborations. The event had a positive impact on data analysis and presentation as well as fund-raising strategies. |
Year(s) Of Engagement Activity | 2014 |
Description | Bridging the Gaps, Living Systems Modelling Event |
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 | An oral presentation (invited) on "peroxisomes in health and disease" at a Bridging the Gaps, Living Systems Modelling Event sparked questions and discussions and supported the formation of interdisciplinary networks. The event supported interdisciplinary networking including cooperative research and competitive fund-raising. |
Year(s) Of Engagement Activity | 2013 |
Description | Cell Biology Theme Event (outreach activity) |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Postgraduate students |
Results and Impact | Approx. 50 participants attended for an open research event to inform about research and projects as well as career development in life sciences, which sparked questions and discussions afterwards, and the participants reported increased interest in related subjects as well as interest in cooperation. |
Year(s) Of Engagement Activity | 2016 |
Description | DGZ Meeting, Cologne, Germany 2015 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | A poster presentation at the 2015 DGZ (German Society for Cell Biology) Annual Meeting, March 24-27, 2015, Cologne, Germany (the largest cell biology meeting in Germany with participants from science, policy, public and health organisations) reached more than 2000 participants and sparked questions, discussions and influenced thinking. Abstract in conference proceedings, new international cooperation and networking opportunities, increased interest in our research onganelle interplay and targeting of membrane proteins |
Year(s) Of Engagement Activity | 2015 |
URL | http://congress.cpb.de/1/Home.586.0.html |
Description | EMBL Hamburg, Germany visit |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | Yes |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Seminar on peroxisomal division, proliferation and dynamics at the EMBL Hamburg, Hamburg, Germany (invited speaker). 30-40 students and scientists attended, which sparked questions and discussions afterwards. A cooperation and supervision was established. Furthermore, I was involved in a panel for selection of Postdoctoral researchers for a research project. |
Year(s) Of Engagement Activity | 2013 |
Description | EU ROS COST action |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | 60-70 professionals attended for an international presentation/discussion event which sparked questions and discussions afterwards and fostered international cooperation. |
Year(s) Of Engagement Activity | 2016 |
Description | GDAP1 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 | Public/other audiences |
Results and Impact | Press Release "Study of the machinery of cells reveals clues to neurological disorder", Research News featuring our publication in EMBO Rep. The press release promoted our recognition in the field and sparked discussions with experts and the public. |
Year(s) Of Engagement Activity | 2013 |
URL | http://www.exeter.ac.uk/news/featurednews/title_290807_en.html |
Description | Glaxo Smith Kline visit |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | A presentation on peroxisome biology and role in health and disease (invited speaker) at Glaxo Smith Kline, Stevenage, UK sparked questions, discussions and thinking. The event has contributed to a link between fundamental research and applied sciences and has inspired thinking about potential industrial applications. |
Year(s) Of Engagement Activity | 2013 |
Description | Groningen Biomolecular Sciences and Biotechnology Institute (GBB) mini-symposium |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | Approx. 50 scientists and students attended a mini-symposium/presentation (invited speaker) on Shapers and Movers in Peroxisome Dynamics, which sparked questions and discussions. The event was combined with a public PhD defence (panel member and external examiner). The event combined public and academic audiences and fostered a general understanding and appreciation of science/organelle biology. |
Year(s) Of Engagement Activity | 2014 |
Description | ISSF seed corn fund and hub services event |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | Yes |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Oral presentation for about 50 participants attending a ISSF seed corn fund and hub services event to foster cooperation and networking and to inform about fund raising and hub activities/possibilities. This event has created new contacts and networking opportunities. |
Year(s) Of Engagement Activity | 2014 |
Description | Medical University of Vienna, Austria |
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 Dynamics in health and Disease, which sparked questions and discussions afterwards and supported decision making. The event stimulated networking and cooperation events and contributed to decision making concerning employment. |
Year(s) Of Engagement Activity | 2014 |
Description | Medical and Health Research Showcase |
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 | Approx. 800 participants attended a poster presentation at a Medical and Health Research Showcase to inform researchers, students and the public about research activities and outcomes at the University of Exeter. This created a lot of awareness and fostered communication with other researchers and the public. The event fostered the local/regional awareness of medical research and supported networking and cooperation. My team received the Best Poster Award which was selected out of > 160 entries. This was a great success and excellent advertisement/awareness for our research. |
Year(s) Of Engagement Activity | 2014 |
URL | http://www.exeter.ac.uk/research/events/healthshowcase/ |
Description | Men In White Schools Initiative |
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 science activity day for year nine students from local schools, which attempts to encourage more young people to pursue science as a career. Science activity day/demonstration reached more than 800 pupils and sparked questions, discussions and career interests. Encouraged pupils to pursue science as a career. |
Year(s) Of Engagement Activity | 2014 |
Description | Microorganisms and Cells |
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 | Approx. 40-50 pupils (yr 6) and teachers attended a lesson and practical on microorganisms and cells (morphology, biological function, common principles, differences, cellular organelles, importance for health, food security and wellbeing), which sparked questions and discussions and made them think about science. The event was very successful and generated high interest, which was communicated in the School newsletter; furthermore, it resulted in another invitation. |
Year(s) Of Engagement Activity | 2014 |
Description | Peroxisome Biogenesis Disorder Family Meeting |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | Family Meeting with patients and carers dealing with peroxisome biogenesis disorders. Presentation about peroxisome research in the UK sparked questions and discussions afterwards, and plans to increase awareness of PBDs in the UK were developed. |
Year(s) Of Engagement Activity | 2016 |
URL | http://www.Zellweger.org.uk |
Description | Press release on membrane dynamics |
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 cell biology with link to biomedicine/human disease with respect to membrane dynamics. It sparked questions and discussions, increased awareness and interest. |
Year(s) Of Engagement Activity | 2018 |
URL | http://www.exeter.ac.uk/research/newsandevents/news/title_635625_en.html |
Description | Press release targeting prediction |
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 cell biology with link to biomedicine/human disease. It sparked questions and discussions, increased awareness and interest. |
Year(s) Of Engagement Activity | 2017 |
URL | http://www.exeter.ac.uk/news/research/title_576535_en.html |
Description | Seminar Univ. of Tuebingen |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Seminar on peroxisomal membrane dynamics in health and disease at the Univ. of Tuebingen, Inst. for Biochemistry, Germany (invited speaker). 40-50 students and scientists attended, which sparked questions and discussions afterwards. A scientific cooperation was established which includes exchange of methods to improve technical skills. |
Year(s) Of Engagement Activity | 2015 |
Description | Seminar at Amsterdam Medical Centre, 2015 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Seminar on peroxisomal dynamics at the Academic Medical centre, Amsterdam, The Netherlands (invited speaker). 30-40 students and scientists attended, which sparked questions and discussions afterwards. A scientific cooperation was established which includes exchange of staff to improve technical skills and exchange of methods. |
Year(s) Of Engagement Activity | 2015 |
Description | Sir Paul Nurse visit |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | Invited lecture and discussion with Sir Paul Nurse including the scientific concept of the new Living Systems Building, which sparked questions and discussions. The event fostered an exchange of ideas and concepts with impact on further decisions/planning. |
Year(s) Of Engagement Activity | 2014 |
Description | Spalding SGS public presentation |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | About 100 people of different ages and sex attended a public presentation about microscopy of the human cell. This sparked questions and discussions afterwards, and the organisation (Spalding SGS) reported increased interest in related subject areas and in fundamental, discovery-based research in general. The general public was informed about fundamental research in cell biology, which increased awareness and influenced thinking. Plans were made for further activities. |
Year(s) Of Engagement Activity | 2016 |
URL | http://www.spalding-gentlemens-society.org/2015-2016_season.html |
Description | University Open Day |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | Yes |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Approx. 250 potential students and their parents/care takers attended a laboratory course which sparked questions and discussions and informed about education and science programs. The event supported decision making and public awareness. |
Year(s) Of Engagement Activity | 2014 |
Description | Visit/Seminar Institute Pasteur, Paris |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | About 50 researchers attended a seminar, which sparked questions and discussions afterwards. There was increased interest in the topic of organelle/peroxisome proliferation and regulation of number and plans for future co-operations. |
Year(s) Of Engagement Activity | 2016 |
Description | Wellcome Trust visit |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | Yes |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | Invited presentation to Wellcome Trust delegates and scientists, which sparked questions and discussions. The event helped to inform decision makers and to secure funding opportunities. |
Year(s) Of Engagement Activity | 2014 |
Description | Workshop Peroxisomes in Health and Disease |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | A series of lectures by leading experts in the filed, discussions and a practical sparked questions and discussions and fostered new research approaches, exchange of knowledge and new partnerships. The event fostered new research approaches, exchange of knowledge and new partnerships (international networking, secondments). |
Year(s) Of Engagement Activity | 2014 |