Investigating a neuronal subcellular transcriptome by the novel technique of RNA TU-tagging, in a normal and ALS-related mouse model.
Lead Research Organisation:
University College London
Department Name: Institute of Neurology
Abstract
Amyotrophic Lateral Sclerosis (ALS, 'motor neuron disease') is a devastating neurodegenerative disorder which causes progressive loss of muscle function and paralysis. ALS leads to death, usually caused by the inability to breathe, on average only 3 years after diagnosis, with a lifetime risk of ~1 in 250 by 85 years old.
The principal cells affected in this disease are nerve cells called motor neurons (MNs). MNs connect the brain to the muscles therefore making movement possible. MNs progressively die during the course of ALS. MNs are amongst the largest cells of the body. Their main body lies in the spinal cord and contains numerous thin branching processes called dendrites. They also have one thin process, named the axon, which extends from the spinal cord out to each of our muscles. A single axon can measure over a meter, running from the spinal cord to ends of our fingers or toes. The connection between the MN and muscles is called the neuromuscular junction (NMJ).
All cells in an individual's body, although very diverse from each other, contain the same DNA, the genetic material that gives instructions to each cell. So the identity of each cell type (whether the cell is a nerve cell or a heart cell, for example) is the result of which regions of DNA are active and produce another type of chemical called RNA. RNA carries all the necessary information for the cell to function. The sum of all the RNA in a cell, named the transcriptome, is the signature that characterizes each cell type.
Knowing one cell transcriptome provides insights into its biology and helps determine the causes of disease. This is particularly relevant with MNs in ALS since there is good evidence showing that the biological processes linked to RNA 'metabolism' are primarily affected in ALS.
Importantly, we now know that RNA is transported and functions in different regions within an individual cell; in MNs it is transported in axons and to NMJs for specific roles. NMJs and axons are thought to be the first parts of the MNs to be affected in ALS.
Therefore it is important to know which RNAs are present in cell bodies and dendrites, and in axons, and at neuromuscular junctions of MNs, to understand how they function normally and what goes wrong in ALS.
It is possible to isolate and identify RNA from neurons and their axons when these are artificially grown in a culture dish or when cell bodies are dissected out under a microscope from fixed tissues. These findings have shown that thousands of different RNA species are actively transported to the axons, but it is difficult from these experiments to extract information that is relevant to mature neurons in their natural context in vivo and therefore to disease.
We will work with a new technique, 'TU-tagging', which has already been successfully used in mouse and which allows us to 'tag' RNA in specific cells in the context of a living animal. The tagged RNA can then be isolated and identified through high-throughput sequencing. We will apply this technique to MNs so for the first time we can isolate and identify RNA from MNs cell bodies and dendrites, and from their axons and NMJs in the living adult mouse.
We will work with normal mice, and with a new mouse model that we have developed that has a defect in a gene, Tardbp (also known as Tdp-43) that causes ALS. From our current work we know defects in this gene give an aberrant RNA profile in the MN cell bodies of this mouse. Currently no Tdp-43 mutant mice exactly model human ALS, but they teach us a great amount about how Tdp-43 functions in the normal and abnormal state.
These results will be extremely helpful in furthering our understanding of MN biology and of what causes these cells to be so specifically vulnerable in ALS.
This project will help research in the many other diseases in which RNA metabolism in different cell regions is important, and in response to nerve injury where again it plays a key role.
The principal cells affected in this disease are nerve cells called motor neurons (MNs). MNs connect the brain to the muscles therefore making movement possible. MNs progressively die during the course of ALS. MNs are amongst the largest cells of the body. Their main body lies in the spinal cord and contains numerous thin branching processes called dendrites. They also have one thin process, named the axon, which extends from the spinal cord out to each of our muscles. A single axon can measure over a meter, running from the spinal cord to ends of our fingers or toes. The connection between the MN and muscles is called the neuromuscular junction (NMJ).
All cells in an individual's body, although very diverse from each other, contain the same DNA, the genetic material that gives instructions to each cell. So the identity of each cell type (whether the cell is a nerve cell or a heart cell, for example) is the result of which regions of DNA are active and produce another type of chemical called RNA. RNA carries all the necessary information for the cell to function. The sum of all the RNA in a cell, named the transcriptome, is the signature that characterizes each cell type.
Knowing one cell transcriptome provides insights into its biology and helps determine the causes of disease. This is particularly relevant with MNs in ALS since there is good evidence showing that the biological processes linked to RNA 'metabolism' are primarily affected in ALS.
Importantly, we now know that RNA is transported and functions in different regions within an individual cell; in MNs it is transported in axons and to NMJs for specific roles. NMJs and axons are thought to be the first parts of the MNs to be affected in ALS.
Therefore it is important to know which RNAs are present in cell bodies and dendrites, and in axons, and at neuromuscular junctions of MNs, to understand how they function normally and what goes wrong in ALS.
It is possible to isolate and identify RNA from neurons and their axons when these are artificially grown in a culture dish or when cell bodies are dissected out under a microscope from fixed tissues. These findings have shown that thousands of different RNA species are actively transported to the axons, but it is difficult from these experiments to extract information that is relevant to mature neurons in their natural context in vivo and therefore to disease.
We will work with a new technique, 'TU-tagging', which has already been successfully used in mouse and which allows us to 'tag' RNA in specific cells in the context of a living animal. The tagged RNA can then be isolated and identified through high-throughput sequencing. We will apply this technique to MNs so for the first time we can isolate and identify RNA from MNs cell bodies and dendrites, and from their axons and NMJs in the living adult mouse.
We will work with normal mice, and with a new mouse model that we have developed that has a defect in a gene, Tardbp (also known as Tdp-43) that causes ALS. From our current work we know defects in this gene give an aberrant RNA profile in the MN cell bodies of this mouse. Currently no Tdp-43 mutant mice exactly model human ALS, but they teach us a great amount about how Tdp-43 functions in the normal and abnormal state.
These results will be extremely helpful in furthering our understanding of MN biology and of what causes these cells to be so specifically vulnerable in ALS.
This project will help research in the many other diseases in which RNA metabolism in different cell regions is important, and in response to nerve injury where again it plays a key role.
Technical Summary
Coding and non-coding RNAs are transported to different subcellular localisations for local translation and regulation. Localised 'RNA metabolism' is important in polarised cells such as neurons, but techniques to study RNA localisation are not able to isolate subcellular transcriptomes in vivo.
Motor neurons (MNs) have cell bodies in the spinal cord, numerous arborizing dendrites and they connect to muscle fibres at the neuromuscular junction (NMJ) through an axon that can exceed 1 meter in length.
We are interested in MNs because of our research into Amyotrophic Lateral Sclerosis (ALS), a fatal neurodegenerative disorder that is characterized by the progressive loss of motor neurons that 'die back' from NMJs. ALS-causative mutations in RNA-binding and -transport genes (TARDBP 'TDP-43', FUS), and in C9ORF72 that induce RNA foci - have highlighted aberrant subcellular RNA metabolism in ALS pathogenesis.
Thus there is a clear need to identify the neuronal subcellular transcriptome in vivo to understand normal function, and dysfunction in our paradigm disease, ALS.
We will use a new technique, 'TU-tagging' (already successful in mouse) to identify the subcellular transcriptome of three compartments of adult motor neurons in normal mouse and in a mouse with a mutation in Tdp-43. Our preliminary data from a Tdp-43 mutant we are characterising shows disruption of many downstream genes including b-synuclein and tau.
TU-tagging works through the cell-specific expression of an enzyme (UPRT) and treatment with a drug (4TU), allowing incorporation of thio-uridine into RNA in specific cell types. Thio-uridine RNA is biotinylated and then pulled-down. We will use TU-tagging to identify RNA from (1) MN cell bodies and dendrites, (2) MN axons, (3) NMJs.
This will allow us insight in the biology of MNs, axons and NMJs and their susceptibility in disease.
TU-tagging is applicable to all models of normal function and disease, and of neuronal injury.
Motor neurons (MNs) have cell bodies in the spinal cord, numerous arborizing dendrites and they connect to muscle fibres at the neuromuscular junction (NMJ) through an axon that can exceed 1 meter in length.
We are interested in MNs because of our research into Amyotrophic Lateral Sclerosis (ALS), a fatal neurodegenerative disorder that is characterized by the progressive loss of motor neurons that 'die back' from NMJs. ALS-causative mutations in RNA-binding and -transport genes (TARDBP 'TDP-43', FUS), and in C9ORF72 that induce RNA foci - have highlighted aberrant subcellular RNA metabolism in ALS pathogenesis.
Thus there is a clear need to identify the neuronal subcellular transcriptome in vivo to understand normal function, and dysfunction in our paradigm disease, ALS.
We will use a new technique, 'TU-tagging' (already successful in mouse) to identify the subcellular transcriptome of three compartments of adult motor neurons in normal mouse and in a mouse with a mutation in Tdp-43. Our preliminary data from a Tdp-43 mutant we are characterising shows disruption of many downstream genes including b-synuclein and tau.
TU-tagging works through the cell-specific expression of an enzyme (UPRT) and treatment with a drug (4TU), allowing incorporation of thio-uridine into RNA in specific cell types. Thio-uridine RNA is biotinylated and then pulled-down. We will use TU-tagging to identify RNA from (1) MN cell bodies and dendrites, (2) MN axons, (3) NMJs.
This will allow us insight in the biology of MNs, axons and NMJs and their susceptibility in disease.
TU-tagging is applicable to all models of normal function and disease, and of neuronal injury.
Planned Impact
The impact of this research lies in two areas (1) understanding the biology of the transcriptome in subcellular locations, (2) amyotrophic lateral sclerosis and the TDP-43 proteinopathies. These two impacts are quite different in that (1) provides a new technique (albeit previously used in mouse) that we believe will become a standard approach to isolating the subcellular transcriptome and so with very broad impact, whereas (2) tackles a biomedical issue, well-known neurodegenerative diseases for which no cure exists.
(1) TU-tagging is a technique that is relevant to every study with a need to catalogue and quantify the localised RNA transcriptome within a cell type. This has obvious application to early development of the Drosophila and mammalian embryos, but also to ALL other studies in which subcellular RNA pools are important.
Therefore we envisage this becoming a standardly used technique, only limited currently by the availability of suitable mouse models. We note that with the number of freely available mice with individual gene mutations and Cre transgenics with precisely defined patterns of expression set to rise dramatically over the next few years, TU-tagging will be very widely applicable to both academic and industrial applications. Knowing the subcellular transcriptome will have impact on academic studies of all areas of biology and also on industry studies for example in highlighting new mechanisms and targets, notably in non-coding RNAs. One immediate application for both academic and commercial interests is in the neuronal response to injury which involves local translation to form a signalling complex that is carried to the cell body.
(2) ALS is a devastating incurable mid-life disorder for which no cure or effective treatment exists. It is clear that localised RNA biology is involved within neurons and so our research will shed light on pathways and networks that are important for motor neuron health and disease. This will have impact on the ALS community.
As our paradigm, we have chosen to work with a Tdp-43 model related to ALS - this gene/protein is also dysfunctional in many common neurodegenerative disorders, including Alzheimer disease and Parkinson disease, and so this project may well also have a wider impact as more commonalities are found in the 'TDP-43 proteinopathy' neurodegenerative diseases, particularly those clearly involving disruption to RNA metabolism disruption.
Thus our findings may benefit biotech/pharma by providing new insights and new targets for the development of therapeutics for ALS, and possibly other RNA disorders. It is intriguing also that several of the new ALS genes also play roles in specific cancers when translocated and so it is possible this research may have an impact on cancer studies also.
We note also that the sub-cellularly localised RNA transcriptome also plays a role in the response to nerve injury and thus our approach should be of interest in studying the impact of neuronal damage.
Finally, increasingly sophisticated techniques are being used for making RNA a therapeutic molecule, and it is likely that in the future knowledge of the localised transcriptome may further refine these efforts.
(1) TU-tagging is a technique that is relevant to every study with a need to catalogue and quantify the localised RNA transcriptome within a cell type. This has obvious application to early development of the Drosophila and mammalian embryos, but also to ALL other studies in which subcellular RNA pools are important.
Therefore we envisage this becoming a standardly used technique, only limited currently by the availability of suitable mouse models. We note that with the number of freely available mice with individual gene mutations and Cre transgenics with precisely defined patterns of expression set to rise dramatically over the next few years, TU-tagging will be very widely applicable to both academic and industrial applications. Knowing the subcellular transcriptome will have impact on academic studies of all areas of biology and also on industry studies for example in highlighting new mechanisms and targets, notably in non-coding RNAs. One immediate application for both academic and commercial interests is in the neuronal response to injury which involves local translation to form a signalling complex that is carried to the cell body.
(2) ALS is a devastating incurable mid-life disorder for which no cure or effective treatment exists. It is clear that localised RNA biology is involved within neurons and so our research will shed light on pathways and networks that are important for motor neuron health and disease. This will have impact on the ALS community.
As our paradigm, we have chosen to work with a Tdp-43 model related to ALS - this gene/protein is also dysfunctional in many common neurodegenerative disorders, including Alzheimer disease and Parkinson disease, and so this project may well also have a wider impact as more commonalities are found in the 'TDP-43 proteinopathy' neurodegenerative diseases, particularly those clearly involving disruption to RNA metabolism disruption.
Thus our findings may benefit biotech/pharma by providing new insights and new targets for the development of therapeutics for ALS, and possibly other RNA disorders. It is intriguing also that several of the new ALS genes also play roles in specific cancers when translocated and so it is possible this research may have an impact on cancer studies also.
We note also that the sub-cellularly localised RNA transcriptome also plays a role in the response to nerve injury and thus our approach should be of interest in studying the impact of neuronal damage.
Finally, increasingly sophisticated techniques are being used for making RNA a therapeutic molecule, and it is likely that in the future knowledge of the localised transcriptome may further refine these efforts.
Organisations
- University College London (Lead Research Organisation)
- UNIVERSITY OF OXFORD (Collaboration)
- AbbVie Inc (Collaboration)
- University College London (Collaboration)
- Hospital Universitario Insular de Gran Canaria (Collaboration)
- University of Padova (Collaboration)
- University of Leuven (Collaboration)
- MRC Harwell Institute (Collaboration)
Publications
Abdelkarim S
(2016)
CHCHD10 Pro34Ser is not a highly penetrant pathogenic variant for amyotrophic lateral sclerosis and frontotemporal dementia.
in Brain : a journal of neurology
Birsa N
(2021)
FUS-ALS mutants alter FMRP phase separation equilibrium and impair protein translation.
in Science advances
Brown AL
(2022)
TDP-43 loss and ALS-risk SNPs drive mis-splicing and depletion of UNC13A.
in Nature
Bunton-Stasyshyn RK
(2015)
SOD1 Function and Its Implications for Amyotrophic Lateral Sclerosis Pathology: New and Renascent Themes.
in The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry
Cortese A
(2014)
Widespread RNA metabolism impairment in sporadic inclusion body myositis TDP43-proteinopathy.
in Neurobiology of aging
De Giorgio F
(2019)
Transgenic and physiological mouse models give insights into different aspects of amyotrophic lateral sclerosis.
in Disease models & mechanisms
Devoy A
(2017)
Humanized mutant FUS drives progressive motor neuron degeneration without aggregation in 'FUSDelta14' knockin mice.
in Brain : a journal of neurology
Fisher E
(2023)
Opinion: more mouse models and more translation needed for ALS
in Molecular Neurodegeneration
Fratta P
(2018)
Mice with endogenous TDP-43 mutations exhibit gain of splicing function and characteristics of amyotrophic lateral sclerosis.
in The EMBO journal
Fratta P
(2014)
Sequencing analysis of the spinal bulbar muscular atrophy CAG expansion reveals absence of repeat interruptions.
in Neurobiology of aging
Fratta P
(2014)
Correlation of clinical and molecular features in spinal bulbar muscular atrophy.
in Neurology
Fratta P
(2015)
Screening a UK amyotrophic lateral sclerosis cohort provides evidence of multiple origins of the C9orf72 expansion.
in Neurobiology of aging
Fratta P
(2014)
Profilin1 E117G is a moderate risk factor for amyotrophic lateral sclerosis.
in Journal of neurology, neurosurgery, and psychiatry
Garone MG
(2021)
ALS-related FUS mutations alter axon growth in motoneurons and affect HuD/ELAVL4 and FMRP activity.
in Communications biology
Joyce PI
(2015)
A novel SOD1-ALS mutation separates central and peripheral effects of mutant SOD1 toxicity.
in Human molecular genetics
Joyce PI
(2016)
Deficiency of the zinc finger protein ZFP106 causes motor and sensory neurodegeneration.
in Human molecular genetics
Lo KK
(2016)
Limited Clinical Utility of Non-invasive Prenatal Testing for Subchromosomal Abnormalities.
in American journal of human genetics
Mizielinska S
(2014)
C9orf72 repeat expansions cause neurodegeneration in Drosophila through arginine-rich proteins.
in Science (New York, N.Y.)
Sivakumar P
(2018)
TDP-43 mutations increase HNRNP A1-7B through gain of splicing function
in Brain
Description | Investigating neuronal RNA localisation and translational deficits as gain of function mechanisms in ALS. |
Amount | £513,524 (GBP) |
Funding ID | MR/R005184/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2017 |
End | 09/2022 |
Description | MRC ResearchGrant (Uprt) MR/K018523/1 |
Amount | £466,205 (GBP) |
Funding ID | MR/K018523/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2014 |
Description | Rosetrees award |
Amount | £9,601 (GBP) |
Organisation | Rosetrees Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2015 |
End | 02/2017 |
Description | Two PhD studentships from internal funding MRC Harwell |
Amount | £120,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 08/2019 |
End | 08/2022 |
Description | Understanding disease mechanism: Sub-cellular translation in motor neurons in health and in amyotrophic lateral sclerosis |
Amount | £16,595 (GBP) |
Funding ID | M438-F1 |
Organisation | Rosetrees Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 05/2017 |
End | 07/2019 |
Title | A new mouse model of motor neuron degeneration (FUS ALS) |
Description | A new genetically engineered mouse model of FUS ALS |
Type Of Material | Model of mechanisms or symptoms - mammalian in vivo |
Year Produced | 2017 |
Provided To Others? | Yes |
Impact | Several labs now working with this model |
Title | Mouse model Sod1 D83G |
Description | Mouse with endogenous mutation in ALS gene (Sod1 D83G) |
Type Of Material | Model of mechanisms or symptoms - mammalian in vivo |
Year Produced | 2011 |
Provided To Others? | Yes |
Impact | Paper submitted currently, after which the mouse will be made freely available. Second paper being written. We anticipate this mouse will be of interest to the ALS research community. |
Title | New mouse models including a new humanised TARDBP model |
Description | New mouse models including a new humanised TARDBP model for neurodegeneration research including creating new mutations. |
Type Of Material | Model of mechanisms or symptoms - mammalian in vivo |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | Too soon |
Title | Two new humanised FUS mutant strains P525L and Q519Ifs |
Description | Fully humanised FUS gene, wildtype, onto which we have added the P525L mutation and, separately in a second strain of mouse, the Q519Ifs mutation, to try to more faithfully models human FUS motor neuron disease/amyotrophic lateral sclerosis. |
Type Of Material | Model of mechanisms or symptoms - mammalian in vivo |
Year Produced | 2019 |
Provided To Others? | Yes |
Impact | These mice have been presented at meetings, they are freely available, but we have not yet published on them. |
Title | UPRT development |
Description | With Pietro Fratta, developing the UPRT transcriptomic analysis system in our mouse models. |
Type Of Material | Technology assay or reagent |
Provided To Others? | No |
Impact | pending |
Title | mouse embryonic stem cells for Down syndrome |
Description | Manipulated mouse embryonic stem cells to model aspects of Down syndrome |
Type Of Material | Cell line |
Year Produced | 2006 |
Provided To Others? | Yes |
Impact | academic papers |
Title | new humanised SOD1 mouse |
Description | A new Humanised mouse model with the human SOD1 gene; this is a wildtype control for when we go forward to put in human amyotrophic lateral sclerosis mutations into SOD1. |
Type Of Material | Model of mechanisms or symptoms - mammalian in vivo |
Year Produced | 2019 |
Provided To Others? | Yes |
Impact | This mouse is freely available and has been presented at meetings, but we have not yet published on it. |
Title | FUS homozygotes MEFs |
Description | Working with a mouse model, an in vivo model, to produce IMMORTILISED cell lines so that we can drop our animal useage. |
Type Of Material | Database/Collection of data |
Year Produced | 2017 |
Provided To Others? | Yes |
Impact | Reduced mouse numbers |
Description | Abraham Acevedo Arozena |
Organisation | Hospital Universitario Insular de Gran Canaria |
Department | La Fundación Canaria Instituto de Investigación Sanitaria de Canarias |
Country | Spain |
Sector | Public |
PI Contribution | PhD student time and effort to develop a new mouse model |
Collaborator Contribution | PhD supervision, DNA analysis, breeding and phenotypic analysis of a cohort of mice. |
Impact | Posters at meetings |
Start Year | 2016 |
Description | Analysis of the FUS mouse translatome, Fratta, UCL |
Organisation | University College London |
Department | Marie Curie Palliative Care Research Department |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | contribution of the unique FUS Delta14 mouse model |
Collaborator Contribution | RiboTagging and ChatCre breeding to pull down polysomes from the Delta14 mouse |
Impact | Multidisiplinary output. No outcomes yet as just started. |
Start Year | 2016 |
Description | FUS humanised mice to U of Leuven |
Organisation | University of Leuven |
Country | Belgium |
Sector | Academic/University |
PI Contribution | The MMON lab and collaborators created humanised FUS mice, sent to a researcher into motor neuron disease in Leuven, and sent prepublication as part of our collaboration. |
Collaborator Contribution | We created the mice for this collaboration, and carried out the initial characterisation. |
Impact | Too soon. |
Start Year | 2021 |
Description | Greensmith lab small animal ephys |
Organisation | University College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We provide novel mouse models of neurological disorders |
Collaborator Contribution | Analysis of nerve and muscle including by electrophysiology; all in mice. |
Impact | Many papers include work from this collaboration. All papers are listed under the relevant grants. |
Description | Humanised TARDBP mice to pharma |
Organisation | AbbVie Inc |
Department | AbbVie (UK) |
Country | United Kingdom |
Sector | Private |
PI Contribution | We created the novel humanised TARDBP mice, with Abraham Acevedo from Spain. |
Collaborator Contribution | The pharma company will use these mice to understand neurodegeneration. |
Impact | Too soon. |
Start Year | 2021 |
Description | Labs at UCL for bespoke mouse models of neurodegeneration |
Organisation | University College London |
Department | Department of Neuroscience, Physiology and Pharmacology |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Genome engineering expertise |
Collaborator Contribution | In depth knowledge of specific forms of neurodegeneration Fratta, Isaacs, Greensmith, Schiavo, Wiseman. |
Impact | None yet. |
Start Year | 2017 |
Description | MMON |
Organisation | MRC Harwell |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Collaboration with the Mouse Models of Neurodegeneration lab at MRC Harwell, analysis of homozygous and heterozygous mice |
Collaborator Contribution | Breeding, inbreeding onto another background, and phenotypic analysis of homozygous and heterozygous mice. |
Impact | Inbred mice on different backgrounds. Cohorts of mice of different ages, sex-matched with littermate controls, wildtype, heterozygous, homozygous, for phenotypic analysis. Analysis of different phenotypes ranging from behavioural through to physiological. |
Start Year | 2017 |
Description | Oxford, London Motor dysfunction in DS mouse models. |
Organisation | University of Oxford |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Crossing, breeding, large cohorts of mouse models of Down syndrome and undertaking considerable phenotypic analysis. Collecting human samples for comparison (spinal cord). |
Collaborator Contribution | Highly specialised analysis of sensory and motor systems. |
Impact | Watson Scales et al 2018 Important and unexpected finding about neurodegeneration in human Down syndrome |
Start Year | 2015 |
Description | UPRT and localised transcript study |
Organisation | University College London |
Department | Institute of Neurology |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Co-grant awardee, mice and space. |
Collaborator Contribution | direct supervision of joint staff |
Impact | pending |
Start Year | 2014 |
Description | studying ribosomal proteins |
Organisation | University of Padova |
Department | Department of Neurosciences |
Country | Italy |
Sector | Hospitals |
PI Contribution | Access to a unique mouse model of FUS ALS (Delta14) |
Collaborator Contribution | Analysis of ribosomal proteins |
Impact | No outputs yet |
Start Year | 2017 |
Description | Keynote at 2023 IMPC meeting Oxford, ALS models |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | INternational meeting of the International Mouse Phenotyping Consortium, 200 (?) attendees, presented our work and our field more broadly to the audience. |
Year(s) Of Engagement Activity | 2023 |
Description | Motor Neurone Disease/ALS Annual Symposium |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Two posters presented at this annual meeting which has an international audience of scientists AND an audience of patients/carers/charity specialists. |
Year(s) Of Engagement Activity | 2020 |
Description | Set up new ALS Seminar Series |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Schools |
Results and Impact | Set up an academic seminar series on Amyotrophic Lateral Sclerosis and similar topics, but as this is open to the lay public we have had a surprising interest and attendance from sixth form pupils and undergraduates. |
Year(s) Of Engagement Activity | 2014 |
Description | Translation in ALS short film (5 minutes) |
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 | We are currently making a short (5 minutes) film about Translation in ALS, for patients and carers and several of the specialist charities. The ALS charities will be able to use this film for raising hope and raising funding, and we will use it to try to gain funds for a longer film, from broadcasters. |
Year(s) Of Engagement Activity | 2022,2023 |
Description | Visit by fundraisers from MNDA |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Fundraisers from MNDA visited to learn more of current research. These people are well-informed on issues regarding MND and care for people with MND, but are not scientists and do not necessarily have easy access to researchers. Better informed fundraisers. |
Year(s) Of Engagement Activity | 2014 |