RNA metabolism in pathology of AOA2/ALS4 neurodegenerative disorders
Lead Research Organisation:
University of Oxford
Department Name: Sir William Dunn Sch of Pathology
Abstract
All living organisms contain genetic information in a form of genes, which code for proteins - key building blocks of life. During the process of gene expression information from the gene, encoded in a DNA sequence is transferred into messenger RNA (transcription) followed by removal of non-coding intervening sequences (splicing), and decoding of this molecule into protein (translation). Each gene expression step is subjected to multiple regulatory events ensuring that the final protein product is correct. Now it became clear that key regulatory elements in gene expression are represented by the RNA. In this research project we will investigate the mechanism underlying the pathology of ataxia oculomotor apraxia type 2 (AOA2) and amyotrophic lateral sclerosis type 4 (ALS4), highly disabling inherited disorders, characterized by degeneration in the brain and spinal cord, causing progressive muscle weakness and finally atrophy. The gene mutated in these diseases encodes a protein called senataxin. Since the discovery of AOA2/ALS4 mutations in 2004, little progress has been made to characterize the function of senataxin protein or molecular mechanisms of AOA2/ALS4 pathology.
To study the function of senataxin protein in human cells, we will combine our expertise in RNA field with cutting edge high throughput technology in gene expression. In particular, we will perform experiments in human cells, which lack senataxin or were derived from patients' tissues. We hypothesise that AOA2/ALS4 pathologies arise due to defects in senataxin function associated with resolving connections between RNA and DNA, appearing during the process of transcription. If RNA/DNA molecules are not resolved properly, their accumulation can be detrimental to the cells causing pathologies. Initially, we will characterise the defects in transcription and RNA processing observed in cells with senataxin mutations using modern technologies analysing whole cell genome. We will also determine if RNA/DNA profile is perturbed in AOA2/ALS4 patients, and how it contributes to neurodegeneration. Furthermore, we will investigate the role of senataxin in transcription and RNA splicing. We will also identify new senataxin-interacting partners and study their contribution towards gene expression process and AOA2/ALS4 pathology.
Our project focuses on the function of senataxin, providing molecular clues for the pathology of AOA2/ALS4 diseases. It's becoming apparent that RNA processing may represent a common pathogenic mechanism involved in many neurodegenerative disorders. Around 50% of all characterised human genetic diseases are associated with inappropriate transcription/RNA processing. This emphasises the importance of fundamental molecular biology approach of our research towards understanding AOA2/ALS4 pathology. Therefore, the development of novel RNA-based therapies, improving the health and quality of life of AOA2/ALS4 and other neurodegenerative patients with defects of RNA processing, is a likely prospect of our research.
To study the function of senataxin protein in human cells, we will combine our expertise in RNA field with cutting edge high throughput technology in gene expression. In particular, we will perform experiments in human cells, which lack senataxin or were derived from patients' tissues. We hypothesise that AOA2/ALS4 pathologies arise due to defects in senataxin function associated with resolving connections between RNA and DNA, appearing during the process of transcription. If RNA/DNA molecules are not resolved properly, their accumulation can be detrimental to the cells causing pathologies. Initially, we will characterise the defects in transcription and RNA processing observed in cells with senataxin mutations using modern technologies analysing whole cell genome. We will also determine if RNA/DNA profile is perturbed in AOA2/ALS4 patients, and how it contributes to neurodegeneration. Furthermore, we will investigate the role of senataxin in transcription and RNA splicing. We will also identify new senataxin-interacting partners and study their contribution towards gene expression process and AOA2/ALS4 pathology.
Our project focuses on the function of senataxin, providing molecular clues for the pathology of AOA2/ALS4 diseases. It's becoming apparent that RNA processing may represent a common pathogenic mechanism involved in many neurodegenerative disorders. Around 50% of all characterised human genetic diseases are associated with inappropriate transcription/RNA processing. This emphasises the importance of fundamental molecular biology approach of our research towards understanding AOA2/ALS4 pathology. Therefore, the development of novel RNA-based therapies, improving the health and quality of life of AOA2/ALS4 and other neurodegenerative patients with defects of RNA processing, is a likely prospect of our research.
Technical Summary
Ataxia oculomotor apraxia type 2 (AOA2) and amyotrophic lateral sclerosis type 4 (ALS4), are highly disabling disorders, characterised by neurodegeneration in the brain and spinal cord, causing progressive muscle weakness and finally atrophy, arising due to mutations in human senataxin protein. Senataxin shares homology with the yeast RNA/DNA helicase Sen1p and it has been suggested that senataxin may be involved in the regulation of gene expression. This research project will uncover molecular function of human senataxin protein using a combination of our expertise in RNA field and the cutting edge high throughput technology. In the first part of this project we will study transcriptional and RNA processing defects associated with AOA2/ALS4 mutations genome-wide. We propose that the function of senataxin in human cells is related to its RNA/DNA helicase function and its ability to unwind RNA/DNA hybrids (or R-loops) formed between nascent RNA transcripts and single stranded DNA template behind the elongating Pol II. We will investigate the effect of senataxin on genome-wide distribution of R-loops and study their contribution to the neurodegenerative phenotype, employing Solexa sequencing following DNA-immuno-precipitation (DIP-seq). Secondly, we will define the molecular functions of R-loops and senataxin in splicing regulation. Finally,we will identify novel RNA and protein senataxin-interacting partners, using mass-spectrometry and iCLIP approach, followed by the study of their function in gene expression and AOA2/ALS4 pathology. The long term goal of our work is to create a foundation for the collaboration between basic and clinical science beneficial to therapeutic advancement of AOA2/ALS4 diseases and development of novel molecular therapies, improving the health and quality of patients' life.
Planned Impact
The outcome of this research project will be beneficial to all AOA2/ALS4 patients affected by mutations in senataxin protein and also to neurologists and clinical geneticists, directly involved in treating these patients. Since the discovery of senataxin mutations in 2004, little is known about genotype/phenotype correlation in AOA2/ALS4 patients, making the correct diagnosis of these diseases in hospital practice quite laborious and difficult. Our work will make a major contribution to this knowledge, making the strategy for diagnosis of these diseases more efficient.
Development of any therapeutic treatments for AOA2/ALS4 patients bas been hampered by the lack of understanding of molecular role of senataxin protein in humans. This project will investigate the function of senataxin in human cells and therefore shed the light on the underlying pathology of AOA2 disease, which may ultimately provide new targets for therapeutic treatment. In the long term, we are hoping to have an impact on treatment practices of these diseases.
Proposed research project will be instrumental in the initiation of public awareness of human genetic disease research and corresponding therapeutic approaches. In particular, during the NIRG, we intend to communicate about the AOA2/ALS4 diseases to patients and healthy individuals through our research publications, scientific presentations and outreach work with the help of University of Oxford and Ataxia UK, Motor Neuron Disease Association and National Ataxia Foundation charities. The results of this research project are likely to have a big impact on the national health, thus enhancing quality of life and health of patients.
Development of any therapeutic treatments for AOA2/ALS4 patients bas been hampered by the lack of understanding of molecular role of senataxin protein in humans. This project will investigate the function of senataxin in human cells and therefore shed the light on the underlying pathology of AOA2 disease, which may ultimately provide new targets for therapeutic treatment. In the long term, we are hoping to have an impact on treatment practices of these diseases.
Proposed research project will be instrumental in the initiation of public awareness of human genetic disease research and corresponding therapeutic approaches. In particular, during the NIRG, we intend to communicate about the AOA2/ALS4 diseases to patients and healthy individuals through our research publications, scientific presentations and outreach work with the help of University of Oxford and Ataxia UK, Motor Neuron Disease Association and National Ataxia Foundation charities. The results of this research project are likely to have a big impact on the national health, thus enhancing quality of life and health of patients.
Organisations
- University of Oxford (Lead Research Organisation)
- UNIVERSITY OF OXFORD (Collaboration)
- University of Sussex (Collaboration)
- University of Toulouse (Collaboration)
- UNIVERSITY OF NOTTINGHAM (Collaboration)
- San Raffaele Hospital (Collaboration)
- Babraham Institute (Collaboration)
- UNIVERSITY OF BIRMINGHAM (Collaboration)
- Curie Institute Paris (Institut Curie) (Collaboration)
- Medical Research Council (MRC) (Collaboration)
- UNIVERSITY OF CAMBRIDGE (Collaboration)
People |
ORCID iD |
Natalia Gromak (Principal Investigator) |
Publications
Gromak N
(2012)
Intronic microRNAs: a crossroad in gene regulation.
in Biochemical Society transactions
Groh M
(2014)
Mechanisms of transcriptional dysregulation in repeat expansion disorders
in Biochemical Society Transactions
Cristini A
(2018)
RNA/DNA Hybrid Interactome Identifies DXH9 as a Molecular Player in Transcriptional Termination and R-Loop-Associated DNA Damage.
in Cell reports
Gromak N
(2013)
Drosha regulates gene expression independently of RNA cleavage function.
in Cell reports
Gromak N
(2014)
Drosha Regulates Gene Expression Independently of RNA Cleavage Function
in Cell Reports
Cristini A
(2019)
Dual Processing of R-Loops and Topoisomerase I Induces Transcription-Dependent DNA Double-Strand Breaks.
in Cell reports
Groh M
(2017)
Senataxin: Genome Guardian at the Interface of Transcription and Neurodegeneration.
in Journal of molecular biology
Cristini A
(2020)
Transcription-dependent DNA double-strand breaks and human disease
in Molecular & Cellular Oncology
Cristini A
(2022)
RNase H2, mutated in Aicardi-Goutières syndrome, resolves co-transcriptional R-loops to prevent DNA breaks and inflammation.
in Nature communications
Kotsantis P
(2016)
Increased global transcription activity as a mechanism of replication stress in cancer.
in Nature communications
Description | Ataxia Uk reserach grant |
Amount | £35,000 (GBP) |
Organisation | Ataxia UK |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 02/2019 |
End | 02/2021 |
Description | Biochemical Society UK |
Amount | £4,000 (GBP) |
Funding ID | Conference grant to support RNA UK 2016 conference, where i was the main organiser |
Organisation | Biochemical Society |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 01/2016 |
End | 02/2016 |
Description | Cancer Research UK Development Fund |
Amount | £15,000 (GBP) |
Funding ID | Not known |
Organisation | University of Oxford |
Sector | Academic/University |
Country | United Kingdom |
Start | 08/2019 |
End | 09/2020 |
Description | Covid-19 mitigation fund |
Amount | £15,000 (GBP) |
Funding ID | BVR01900 |
Organisation | University of Oxford |
Sector | Academic/University |
Country | United Kingdom |
Start | 01/2021 |
End | 08/2021 |
Description | EPA research COVID disruption grant |
Amount | £34,000 (GBP) |
Funding ID | RF-286 |
Organisation | University of Oxford |
Sector | Academic/University |
Country | United Kingdom |
Start | 06/2020 |
End | 06/2023 |
Description | EPA research grant |
Amount | £134,432 (GBP) |
Funding ID | RF279 |
Organisation | University of Oxford |
Sector | Academic/University |
Country | United Kingdom |
Start | 06/2020 |
End | 06/2022 |
Description | John Fell Research Award |
Amount | £93,958 (GBP) |
Funding ID | BVD07340 |
Organisation | University of Oxford |
Sector | Academic/University |
Country | United Kingdom |
Start | 09/2014 |
End | 10/2016 |
Description | John Fell research grant |
Amount | £9,500 (GBP) |
Funding ID | BVD00120 |
Organisation | University of Oxford |
Sector | Academic/University |
Country | United Kingdom |
Start | 01/2021 |
End | 01/2022 |
Description | Lundbeck Foundation Fellowship |
Amount | 551,313 kr. (DKK) |
Funding ID | R126-2012-12263 |
Organisation | Lundbeck Foundation |
Sector | Charity/Non Profit |
Country | Denmark |
Start | 11/2013 |
End | 11/2015 |
Description | Medical Sciences Division Medical Research Fund |
Amount | £10,000 (GBP) |
Funding ID | Not known |
Organisation | University of Oxford |
Sector | Academic/University |
Country | United Kingdom |
Start | 08/2019 |
End | 09/2020 |
Description | National Ataxia Foundation Research Pilot Grant |
Amount | $14,600 (USD) |
Organisation | National Ataxia Foundation |
Sector | Charity/Non Profit |
Country | United States |
Start | 09/2009 |
End | 10/2010 |
Description | Returning Carers' Fund |
Amount | £5,000 (GBP) |
Organisation | University of Oxford |
Sector | Academic/University |
Country | United Kingdom |
Start | 05/2018 |
End | 01/2019 |
Description | Rosetrees grant award |
Amount | £40,000 (GBP) |
Funding ID | M828 |
Organisation | Rosetrees Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 02/2019 |
End | 02/2021 |
Description | Royal Society International exchanges research fund |
Amount | £10,000 (GBP) |
Funding ID | IES\R1\201138 |
Organisation | The Royal Society |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 08/2020 |
End | 09/2022 |
Description | Royal Society Research Fellows Enhancement Award |
Amount | £100,000 (GBP) |
Funding ID | RG/EA/180023 |
Organisation | The Royal Society |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 12/2017 |
End | 03/2021 |
Description | Royal Society Research grant |
Amount | £14,400 (GBP) |
Organisation | The Royal Society |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 09/2012 |
End | 10/2013 |
Description | Royal Society University Research Fellowship |
Amount | £496,345 (GBP) |
Organisation | The Royal Society |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 09/2011 |
End | 10/2016 |
Description | Royal Society University Research fellowship extension |
Amount | £333,000 (GBP) |
Funding ID | URF150656 |
Organisation | The Royal Society |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 09/2016 |
End | 09/2019 |
Title | R-loop immunoprecipitation |
Description | This methodology was developed in the group to identify R-loop-binding factors (R-loop proteome) in unbiased way from human cells |
Type Of Material | Technology assay or reagent |
Year Produced | 2018 |
Provided To Others? | Yes |
Impact | Great impact in the field of R-loop biology, in health and disease conditions. This technique will be indispensable when studying the biology of R-loop-binding factors |
Title | R-loop proteome database |
Description | The R-loop proteome contains R-loop binding proteins of high confidence in HeLa cells. It is currently deposited into publically available PRIDE database |
Type Of Material | Database/Collection of data |
Year Produced | 2018 |
Provided To Others? | Yes |
Impact | This database will allow the researches to have information about R-loop-binding factors in HeLa cells |
Description | Collaboration on DHX9 protein in Huntington's disease |
Organisation | University of Cambridge |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We are providing our expertise in DHX9 protein and R-loop biology |
Collaborator Contribution | Our partners are doing experiments in iPSc HD cells to test the role of DHX9 in Huntington's disease |
Impact | We are still at the stage of doing experiments |
Start Year | 2021 |
Description | Collaboration on FRDA project |
Organisation | Medical Research Council (MRC) |
Department | MRC Clinical Sciences Centre (CSC) |
Country | United Kingdom |
Sector | Public |
PI Contribution | We carried out nascent transcriptional analysis on FXN gene for this collaboration |
Collaborator Contribution | The whole project is driven by group in Imperial College London |
Impact | Currently we are preparing paper for PLOS Genetics, describing the results of our collaborative work |
Start Year | 2013 |
Description | Collaboration on R-loop project related to generation of large deletions |
Organisation | University of Sussex |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We provided our expertise in R-loop biology and specifically carrying out DIP experiments |
Collaborator Contribution | The collaborators are really driving this project |
Impact | We have just published a paper together: Large XPF-dependent deletions following misrepair of a DNA double strand break are prevented by the RNA:DNA helicase Senataxin. Brustel J, Kozik Z, Gromak N, Savic V, Sweet SMM. Sci Rep. 2018 Mar 1;8(1):3850. doi: 10.1038/s41598-018-21806-y. |
Start Year | 2016 |
Description | Collaboration on RNase H2 |
Organisation | San Raffaele Hospital |
Country | Italy |
Sector | Hospitals |
PI Contribution | We provide expertise in R-loop biology and genome-wide approaches to study RNase H2 enzyme |
Collaborator Contribution | Our collaborators provide the expertise in generation of neuronal cells with Rnase h2 mutations. |
Impact | We are currently generating the scientific data on the project |
Start Year | 2019 |
Description | Collaboration on post-translational modifications of R-loops |
Organisation | University of Nottingham |
Department | University of Nottingham Museum |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We are providing the expertise and reagents required for the study of R-loops |
Collaborator Contribution | Our partners are providing the expertise on m6A post-translational modifications |
Impact | The results of this collaboration are published (Abakir et al Nature Genetics 2020) |
Start Year | 2018 |
Description | Collaboration on the R-loop -related function of SETX protein in hypoxia |
Organisation | University of Oxford |
Department | CRUK/MRC Oxford Institute for Radiation Oncology |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | My lab provides the expertise in SETX protein and R-loop biology. we have also provided some reagents (constructs) required for this project. |
Collaborator Contribution | The partners provide expertise in hypoxia |
Impact | We are in the process of generating the data for the paper |
Start Year | 2019 |
Description | Collaboration on the mechanisms of double strand break formation in non-replicating cells |
Organisation | University of Toulouse |
Country | France |
Sector | Academic/University |
PI Contribution | We provide the expertise and reagents required to study R-loops |
Collaborator Contribution | The partners provide the expertise in double strand breaks |
Impact | We have published a collaborative paper describing the results of this study (Cristini et al Cell Reports 2019) |
Start Year | 2018 |
Description | Collaboration on the role of R-loops , XPG and XPF proteins in centromere biology |
Organisation | University of Oxford |
Department | Sir William Dunn School of Pathology |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | My lab is contributing with expertise in R-loop field and also various reagents (cell line and antibodies) required for the success of this project. |
Collaborator Contribution | The partners are carrying experiments related to the understanding of the centromere biology |
Impact | We are stil at the stage of doing experiments |
Start Year | 2020 |
Description | Collaboration on the role of R-loops in Hippo signalling pathway (with Dafni Pefani, from Eric O'Neil' s lab , Univeristy of Oxford) |
Organisation | University of Oxford |
Department | Rudolf Peierls Centre for Theoretical Physics |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We contribute with our expertise and various reagents available in the lab related to R-loop biology |
Collaborator Contribution | The partners provide a contribution to the study of HIppo signalling pathway, which is their primary expertise. |
Impact | There is no outputs yet. |
Start Year | 2018 |
Description | Collaboration with the group of Prof. wolf Reik (Babraham Institute) |
Organisation | Babraham Institute |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We will contribute with our expertise in R-loop biology |
Collaborator Contribution | I have started a collaboration with the group of Prof. Wold Reik on R-loops in sperm. Wolf Reik will contribute their expertise in spermatogenesis in mice. |
Impact | No outputs just yet |
Start Year | 2021 |
Description | Identifying new molecular mechanisms of replication stress for cancer therapy |
Organisation | University of Birmingham |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We are carrying out DIP procedure following RAS -driven induction in human cells |
Collaborator Contribution | This project is fully driven by our collaborators, we are contributing with the DIP technique established in our lab |
Impact | We have published a paper together: Increased global transcription activity as a mechanism of replication stress in cancer. Kotsantis P, Silva LM, Irmscher S, Jones RM, Folkes L, Gromak N, Petermann E. Nat Commun. 2016 Oct 11;7:13087. doi: 10.1038/ncomms13087. |
Start Year | 2014 |
Description | Role of ATRX in R-loop biology |
Organisation | University of Oxford |
Department | Weatherall Institute of Molecular Medicine (WIMM) |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We are testing the role of R-loops in ATRX recruitment. In particular, we are carrying out DIP experiments in RNase H1 knock-down cells |
Collaborator Contribution | Our collaborators established the importance of R-loops in recruitment to ATRX protein |
Impact | We have provided some advice on carrying out R-loop experiments. |
Start Year | 2015 |
Description | Role of PRMT1 protein in R-loop biology |
Organisation | Curie Institute Paris (Institut Curie) |
Country | France |
Sector | Academic/University |
PI Contribution | We are currently using DIP experiments to study the contribution of PRMT1 to R-loop biology in triple-negative cancer cell lines |
Collaborator Contribution | Our collaborators have generated PRMT1 KD cells and purified genomic DNA samples for us to do DIP experiments. |
Impact | We are hoping to write a joint paper by the end of 2016 |
Start Year | 2015 |
Description | 8th Internatoional conference in unstable mictosatellites and human disease. Guanacaste, Costa Rica |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Participants in your research and patient groups |
Results and Impact | My presentation sparked questions and discussions and I have established a number of important collaborations A couple of students and Post-docs approached me because they were interested in joining my lab. |
Year(s) Of Engagement Activity | 2015 |
URL | http://www.microsatellites.ca/ |
Description | Cold Spring Harbour, USA, RNA processing conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Poster presentation entitled 'The R-loop proteome in human cells'. My presentation sparked discussion with scientists working in the same field and as a result of this I started a couple of collaborations |
Year(s) Of Engagement Activity | 2015 |
Description | Conference presentation |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Conference presentation at ,RNA and disease, conference in Windsor 2016 |
Year(s) Of Engagement Activity | 2016 |
Description | Conference presentation at 'Transcription- replication crosstalk' in ROSCOFF, France |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | Conference talk which stimulated collaborative work with other researchers |
Year(s) Of Engagement Activity | 2016 |
Description | International Reseacrh Ataxia Conference |
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 | Talk presentation entitled 'R-loop Function in pathology of Friedreich ataxia and implications for other expansion diseases' at the International Ataxia Research conference, Windsor, UK. The presentation has resulted in exchange of scientific ideas with my colleagues working in the same field and establishment of new scientific collaborations |
Year(s) Of Engagement Activity | 2015 |
Description | Invitation to chair a session at a EMBO workshop on RNA and genome maintanence: Cooperation and conflict resolution. Mainz, Gemany. October 2018 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | I was invited to chair session on R-loops by the conference organizers. |
Year(s) Of Engagement Activity | 2018 |
URL | http://meetings.embo.org/event/18-rna-genome |
Description | Invited Seminar Department of Biochemistry, University of Cambridge |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | Invited Departmental seminar entitled: R-loops: unusual RNA/DNA structures and their role in health and disease' at the Department of Biochemistry, University of Cambridge. This seminar has allowed scientific discussions with people working in different fields and resulted in exchange of scientific reagents |
Year(s) Of Engagement Activity | 2015 |
Description | Invited at Hallmarks of cancer conference |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Study participants or study members |
Results and Impact | Invited talk entitled ' The R-loop proteome uncovers novel links between genome instability and human disease' at the International symposium: Hallmarks of cancer: focus on RNA. Institute Curie, Paris, France (October 2015). My talk spackled a lot of scientific discussions and as a result of this presentation I established important collaboration. |
Year(s) Of Engagement Activity | 2015 |
Description | Invited departmental seminar at the Dunn School of Pathology |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | Yes |
Geographic Reach | Local |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | I established new collaborations and received very good suggestions to carry out certain experiments A number of students were interested in visiting my lab and carrying out their rotation projects with me |
Year(s) Of Engagement Activity | 2014 |
Description | Invited presentation at the regional Royal Society, 19th February 2015 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | Exchanged ideas with Royal Society current and past Fellows. Established collaborations outside of my area of expertise Established collaborations outside of my area of expertise |
Year(s) Of Engagement Activity | 2015 |
Description | Invited seminar at York University |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | I was invited to speak at York University. This seminar has sparked collaborations afterwards |
Year(s) Of Engagement Activity | 2021 |
Description | Invited seminar at the Institute of Neurology, University College London (UK). |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | Yes |
Type Of Presentation | Paper Presentation |
Geographic Reach | Local |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | Departmental seminar at the Institute of Neurology, University College London (UK). Talk: RNA biology in neurodegeneration. Establishment of collaborations. As a result of this seminar, i was asked to write a review on the topic of my seminar for PLOS Genetics journal |
Year(s) Of Engagement Activity | 2012 |
Description | Invited seminar at the San Raffaele Telethon Institute for Gene Therapy, Milan, November 2019 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | Invited seminar which sparked new discussions and established new collaborations |
Year(s) Of Engagement Activity | 2019 |
Description | Invited seminar at the Vertex Pharmaceuticals, January 2018 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Third sector organisations |
Results and Impact | Invited seminar at a pharmaceutical company to discuss potential collaborative avenues of research and discuss the current state of the field |
Year(s) Of Engagement Activity | 2018 |
Description | Invited seminar in Kings College London (Department of Basic and Clinical Neuroscience) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Supporters |
Results and Impact | My talk stimulated conversations about potential future collaborations Post-graduate students were interested to join my laboratory |
Year(s) Of Engagement Activity | 2014 |
Description | Invited speaker at a conference ;3;end formation; Oxford, 20-24 September 2017 |
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 lot of collaborative work has appeared due to my presentation at this conference |
Year(s) Of Engagement Activity | 2017 |
Description | Invited speaker at symposium ' It takes two to tango: RNA and DNA in genome integrity'. University of Texas, Austin |
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 | I was invited to speak at the symposium ' It takes two to tango: RNA and DNA in genome integrity'. University of Texas, Austin. This presentation has generated new collaborative opportunities. |
Year(s) Of Engagement Activity | 2021 |
Description | Invited speaker at the ,Genome Dynamics in Neuroscience and Aging' herzliya, Israel, April 7-11, 2019 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Invited talk was well received and was followed by many questions form the audience. It sparked a lot of discussions afterwards and new collaborations were established. |
Year(s) Of Engagement Activity | 2019 |
Description | Invited speaker at the ACT RNA club, Australian National University |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | I was invited to give a seminar at the the ACT RNA club, Australian National University. New collaborations have sparked following this seminar. |
Year(s) Of Engagement Activity | 2021 |
Description | Invited speaker at the London RNA club, April 2016 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | This activity resulted in establishment of new collaborators |
Year(s) Of Engagement Activity | 2016 |
Description | Invited talk at RNase H conference, Edinburgh (UK). |
Form Of Engagement Activity | Scientific meeting (conference/symposium etc.) |
Part Of Official Scheme? | Yes |
Type Of Presentation | Paper Presentation |
Geographic Reach | International |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | RNase H conference, Edinburgh (UK). Role of RNA/DNA hybrids over expanded trinucleotide repeats in transcriptional regulation in Friedreich ataxia and Fragile X syndrome. Exchange of scientific ideas, new collaborations |
Year(s) Of Engagement Activity | 2012 |
Description | Invited talk at the 'Genome instability: when RNA meets chromatin' Roscoff, France, 16-20 September 2019 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | This presentation sparked a lot interest in the audience which was followed by discussions and new collaborations established |
Year(s) Of Engagement Activity | 2019 |
Description | Invited talk at the 'RNA meets DNA' conference in Baeza, Spain |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | Yes |
Geographic Reach | International |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | I established a number of very interesting collaborations with international researches I was able to share the results of my research with wider international community |
Year(s) Of Engagement Activity | 2014 |
Description | Invited talk at the RNA UK 2020 Conference, Windermere, Ambleside, UK, January 2020 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | Initvation to speak at the RNA UK 2020 conference. The talk resulted in establishment of new collaborations |
Year(s) Of Engagement Activity | 2020 |
Description | Invited talk at the RNA UK 2022 conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Other audiences |
Results and Impact | New collaborations were established. The research carried out in the group has received a lot of external exposure. |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.rnauk.org/?msclkid=e2a48a99a5d411ec89fdf37ea4b292f6 |
Description | Lecturing at Graduate GABBA course 'Regulation of Gene Expression', University of Porto (Portugal) |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | Yes |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | 2010-2015 Graduate GABBA course 'Regulation of Gene Expression'. Delivering lectures and paper dissections to the 1st year PhD students in Molecular and Cell biology. University of Porto (Portugal). Exposure of students from Portugal to cutting edge research in Gene expression. |
Year(s) Of Engagement Activity | 2010,2011,2012,2013,2014,2015 |
Description | Presentation at International Ataxia Research Conference, 25-28 May 2015 |
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 | My presentation stimulated establishment of collaborations I have met a number of interesting researchers and exchanged scientific ideas. |
Year(s) Of Engagement Activity | 2015 |
URL | https://www.ataxia.org.uk/international-research-conference |
Description | Presentation at Oxford Ataxia Group meeting, University of Oxford |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | Yes |
Type Of Presentation | Paper Presentation |
Geographic Reach | Local |
Primary Audience | Participants in your research and patient groups |
Results and Impact | Presentation at Oxford Ataxia Group meeting. Title: Molecular function of human senataxin protein in pathology of AOA2/ALS4 diseases. Exchange of scientific ideas |
Year(s) Of Engagement Activity | 2011 |
Description | Presentation at the Oxford Transcription Meeting |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | Presentation entitled 'Transcriptional mis-regulation in neurodegenerative disorders' at the Oxford Transcription Meeting. The presentation resulted in exchange of scientific information with Oxford colleagues working in transcription field. |
Year(s) Of Engagement Activity | 2015 |
Description | Presentation at the Oxford Transcription meeting, December 2017 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | Presentation resulted in establishment of new collaborations and sharing of unpublished information |
Year(s) Of Engagement Activity | 2017 |
Description | Presentation at the Royal Society Regional conference |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Study participants or study members |
Results and Impact | Presentation entitled ,Neurodegenerative diseases' at the Royal Society regional conference. University of Oxford. The study stimulated scientific discussions with other Royal Society fellows from different disciplines |
Year(s) Of Engagement Activity | 2015 |
Description | RNA UK 2016 conference |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | Presentation entitled 'The R-loop interactome in Human Cells' at the RNA UK Conference, Windermere, UK (January 2016). This presentation resulted in exchange in scientific data and establishment of scientific collaborations. |
Year(s) Of Engagement Activity | 2016 |
Description | Research Seminar at the Department of Clinical Neurosciences, Kings College London, March 2021 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Postgraduate students |
Results and Impact | I have established new collaborations through discussions after my seminar |
Year(s) Of Engagement Activity | 2021 |
Description | Royal Society Early Career Researchers Workshop. June 2018 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Other audiences |
Results and Impact | Workshop organized by the Research Services of the University of Oxford, who invited me t speak about my Royal Society University Research Fellowship to Post-docs who were interested in applying for similar Career development opportunities. |
Year(s) Of Engagement Activity | 2018 |
Description | Royal Society Research Conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | Following my talk at this conference, i established new collaborations with people outside of my field I learned a lot about research in other fields and established new collaborations |
Year(s) Of Engagement Activity | 2014 |
Description | Royal Society Research Conference , Meeting of the minds'. June 2018. |
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 | Conference organized by a Royal Society. New collaborations established. |
Year(s) Of Engagement Activity | 2018 |
Description | Science outreach for ataxia patients |
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 | Around 50 patients attended 2015 Ataxia UK Annual Conference" 2nd - 3rd October 2015 and my student Matthias Groh presented the poster at the "Meet the Researchers - 10 ataxia researchers discuss their work" session on the 3rd October. This presentation sparked the discussion with patients, and resulted in their better understanding of the ataxia and its underlying molecular mechanisms |
Year(s) Of Engagement Activity | 2015 |
Description | Seminar in the Dunn School of Pathology, University of Oxford |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | Invited seminar at the Dunn School of Pathology. The audience was other researchers, post-graduate students. The talk has sparked discussions. |
Year(s) Of Engagement Activity | 2022 |
Description | Seminar in the University of Birmingham |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Postgraduate students |
Results and Impact | This activity resulted in establishment of new collaborations |
Year(s) Of Engagement Activity | 2016 |
Description | Seminar invitation: Unviersity of Nottingham. May 2018 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | Invited Departmental Seminar on biology of R-loops at the Nottingham University, Wolfson Center for Stem Cells, Tissue Engineering and Modelling (STEM). My seminar resulted in establishment of collaboration with the group of Dr. Alexey Ruzov. |
Year(s) Of Engagement Activity | 2018 |
Description | Seminar invitationg: CR-UK /MRC Oxford Institute for Radiation Oncology. June 2018. |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | Invited seminar at the CR-UK /MRC Oxford Institute for Radiation Oncology. June 2018. New ideas were discussed and collaborations established. |
Year(s) Of Engagement Activity | 2018 |
Description | Seminar on R-loop biology in Montpellier, France |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | My seminar of R-loops sparked lively discussion and established new collaborative projects |
Year(s) Of Engagement Activity | 2019 |
Description | Talk at Oxford Ataxia Group Meeting, University of Oxford |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | Yes |
Type Of Presentation | Paper Presentation |
Geographic Reach | Local |
Primary Audience | Participants in your research and patient groups |
Results and Impact | Presentation at Oxford Ataxia Group Meeting. Title: R-loops in transcriptional regulation of trinucleotide expansion diseases. Exchange of scientific ideas |
Year(s) Of Engagement Activity | 2012 |